BioHybrid Graft I-Corps@NIH 121014

Team 21

Bio-Hybrid Vascular GraftLessons LearnedOctober 10th 2014

104 TOTAL INTERVIEWS

Unmet Need: Small diameter (<6mm) vascular grafts that are ready-to-use and do not clot.

Value: A clinical solution for patients where harvesting autologous graft is not an option.

Unique Design: Biodegradable polymer with proprietary human analog coating (HuBiogel) to generate new blood vessels.

BIO-HYBRID VASCULAR GRAFT

Vascular Grafts for

Regeneration of Blood

Vessels

Project Team

Steve Ceulemans,

MS, MBAIndustry Expert

Birmingham Business Alliance

Biotech start-up experience

Industry analyst

Raj Singh,

Ph.D.CEO

Vivo Biosciences Inc.

VC-backed biotech company

Regenerative biology expert

Yogesh Vohra

Ph.D.PI

University of Alabama at Birmingham

Director, Center for Nanoscale Materials and Biointegration

Biomaterials expert

Initial Canvas

PARTNERS

UAB University Center for Nanoscale materials and Biointegration(electrospinningbiodegradable scaffold)

Vivo Bioscience HuBiogelproprietary human analog coating

ACTIVITIES

STTR Phase I

RESOURCE

IP / know-howUAB electrospinning, analytical , and animal facilities

Vivo HuBiogel

PROPOSITIO

Ready-to-use (no vascular harvesting)

Low thrombogenicity

Small diameter possible (<6mm)

CUSTOMER

RELATIONSHIP

Medical Scientific Liaison (MSL)

Health outcomes / Cost effectiveness

Formulary / reimbursement

CHANNELS

Sales reps

Distributors

CUSTOMER

SEGMENTS

Cardiothoracic surgeons

Vascular surgeons

Patients

Payors(insurance)

Providers (hospitals)

REVENUEGrants Sales

COST STRUCTURER&D Overhead

Better cardiac bypass grafts

VALUE PROPOSITION

Low thrombogenicity

CUSTOMER

SEGMENTS

Vascular surgeons

Patients

Payors (insurance)

and learned… We are in the vascular interventional

devices marketCoronary and peripheral technologies including balloons, stents, grafts, IVC filters, IVUS & angiography catheters, plaque modification devices, hemodynamic flow alteration devices, and accessory devices.

Our Served Available Market: Vascular grafts <6mmCoronary Artery Disease - CAD Grafts

Peripheral Artery Disease - PAD GraftsHemodialysis (AV Grafts)

We got out of the buildingand met with our first customers...

$800M (estim.)

$10.5B

1,000-2,000 cases/year.

Typically initial corrective surgery with synthetic graft followed by permanent intervention later in life.

An interesting application popped up

Pediatric congenital heart disease grafts

POSSIBLE OPPORTUNITY:

FDA offers special support for pediatric technologies.

There is a special FDA Humanitarian Device Exemption

(HDE) for technologies serving less than 2,000

patients/year.

Only need to show safety, not efficacy

Revised Canvas 1

PARTNERS

University (UAB)

Material suppliers

GMP Manufacturing

Regulatory / Reimbursement

ACTIVITIES

Preclinical validation

Animal Data

Human Data

RESOURCES

Biopolymer

HuBiogel

Electrospinning

PROPOSITIO

3x Less thrombogenic

Minimal immunogenic

Surgery ready

Smaller diameter possible (<6mm)

Dynamic (grows with patient)

CUSTOMER

RELATIONSHIP

Medical Scientific Liaison

Cost effectiveness

CHANNELS

Sales reps

Distributors

CUSTOMER

SEGMENTS

(Vascular) surgeons

Pediatric surgeons

Patients

Payors(insurance)

REVENUECoronary Artery Disease – CAD graftsPeripheral Artery Disease – PAD graftsHemodialysis grafts

COST STRUCTURER&D IPPreclinical & Humanclinical development capital

Target market: 4 possible segments

Coronary artery disease graftsPediatric congenital disease grafts

Peripheral artery disease graftsHemodialysis (AV) grafts

PARTNERS

VALUE PROPOSITION

Minimal immunogenic

Surgery ready

CUSTOMER SEGMENTS

(Vascular) surgeons

Pediatric surgeons

Patients

Payors (insurance)

Providers (hospitals

REVENUECoronary Artery Disease – CAD grafts

Peripheral Artery Disease – PAD grafts

Hemodialysis grafts

Customer discovery: Customer segments“A vascular surgeon is never the first doctor you see, the clinical team/process can heavily influence the care you receive”

USER INFLUENCER DECISION MAKER ECONOMIC BUYER

Possible Saboteurs

Patient

Primary Care

ER Physician

Internist

Cardiologist

Nephrologist

Interventional Cardiologist/

radiologist

Vascular surgeon

Cardiothoracic surgeon

P&T CommitteeBundled Payment

Revised Canvas 2

PARTNERS

Strategic marketing partner

University (UAB)

Material suppliers

Investors

ACTIVITIES

Animal Data

Human Data

RESOURCES

Grants/contracts

Equip. supplies

Consultants

PROPOSITIO

Coronary grafts with longer life than saponous vein grafts (>5Y)

AV Graft / Fistula with more than 50% maturation rate

Limb ischemia graft with better patency rates than stents

Dynamic pediatricgrafts that only need single surgery

CUSTOMER

RELATIONSHIP

Clin. opinion leader

Pub. Agreements

Patient advocacy

CHANNELS

Sales reps

Strategic marketing partnership

Distributors

CUSTOMER

SEGMENTS

Cardio + vasc. surgeons

Pediatric surgeons

Hemodialysis doctors

Interventionalcardiologist radiologist

Patients

Payors(insurance)

New influencers and decision makers:

CardiologistHemodialysis doctors

Interventional cardiologist/radiologist

PARTNERS

PROPOSITION

Coronary grafts with longer life than saponousvein grafts (>5Y)

Dynamic pediatric grafts that only need single surgery

CUSTOMER

SEGMENTS

Pediatric surgeons

Patients

Payors (insurance)

CUSTOMER

RELATIONSHIP

Pub. Agreements

Patient advocacy

Regulatory

“The only way to get human data for an innovative device like this in the U.S. is to bring

human data”

“Controlled polymer degradation and regeneration

is a tough test to design”

Pre-Clinical Clinical

Precedents in

Poland and HungaryMost recent:

40 patients, 3 sites

Revised Canvas 3

PARTNERS

University (UAB)

GMP Compliant CMO

Investors

Clinical Opinion leaders/ champions

ACTIVITIES

Discovery Research & Precl. validation

Animal Data

CE followed by FDA

GLP / GMP

RESOURCES

Grants/contracts

Equip. supplies

Consultants

PROPOSITIO

CUSTOMER

RELATIONSHIP

Pub. Agreements

Patient advocacy

CHANNELS

Distributors

CUSTOMER

SEGMENTS

Pediatric surgeons

Patients

Payors(insurance)

COST STRUCTURER&D & Preclin. Dev. IPclinical development ConsultantsMaterial & Equip. Human capital

REVENUEStrategic marketing partnership royaltiesRevenue from pilot programs / trialsSales revenue from distributors

Talked to EU regulatory experts and Updated

canvas

Preclinical milestone: pig carotid dataCE mark in EU (Poland) first

Clinical milestones:restenosis

Peak walking test

PARTNERS

KEY PARTNERS

University (UAB)

GMP Compliant CMO

Investors

KEY ACTIVITIES

Animal Data

CE followed by FDA

GLP / GMP

COST STRUCTURE

R&D & Preclin. Dev. IP

clinical development ConsultantsMaterial & Equip. Human capital

Prioritizing Target Markets

MON TUE WED

We learned a lot more about our market:

CORONARY ARTERY

DISEASE

PERIPHERAL ARTERY

DISEASEHEMODIALYSIS

Innovation

“There’s this great vascular intervention conference you should consider”

Customer Feedback: Prioritizing Applications

“Coronary bypass is the absolute worst clinical

application to pursue, the procedure is complicated and if anything goes wrong there

are no easy fixes”

“Peripheral artery disease has seen some recent innovations and commercial successes, so

this market is hot; and there is still an unmet need within a

market looking to evolve”

“There are no precedent commercial successes using the HDE/pediatric pathway,

combined with neonatal intervention advances, this will be a very difficult path”

“There will be an expectation of equal performance to

synthetic AV grafts, which can be used 3 weeks after

placement”

Final Canvas

PARTNERS

University (UAB)

GMP Compliant CMO

Investors

ACTIVITIES

Research & Precl. validation

Animal Data

CE before FDA

GLP / GMP

Strategic partners

RESOURCES

Grants/contracts

Equip. / supplies

Know-how

Consultants

PROPOSITIO

Ready-to-use, small diameter (<6mm) vascular graft where there is currently no alternative.

CUSTOMER

RELATIONSHIP

Pub. Agreements

Patient advocacy

Health outcomes / cost effectiveness

CHANNELS

Distributors

CUSTOMER

SEGMENTS

Vascular surgeons

Referring physicians

Hospital P&T Committee

Payors(insurance)

Patients

Re-prioritized markets

1. PAD2. Hemodialysis3. CAD4. Congenital Heart disease

Pivot: CAD to PAD Grafts

Customers: Referring physicians are key influencers

Regulatory: Pre-clinical pig data; clinical CE mark in EU

followed by FDA

Reimbursement: ~$1,000

Next Step: Apply for STTR Phase II Spring 2015 with

nominal pivot.

Summary

and next steps

Medical Device

Investment Readiness

Reimbursement

Effective team?

Attractive solution & ID of MVP

Unit economics Validated

Cash to exit

Plausible exit

Compelling clinical need + large market

Intellectual Property

Regulatory

Started IRL 2

Ended IRL 4.5

https://www.youtube.com/w

atch?v=9bokuAtBJgg

Canvas

Progress

Initial Canvas

PARTNERS

ACTIVITIES

STTR Phase I

RESOURCE

IP / know-howUAB electrospinning, analytical , and animal facilities

Vivo HuBiogel

PROPOSITIO

Low thrombogenicity

CUSTOMER

RELATIONSHIP

Medical Scientific Liaison (MSL)

Health outcomes / Cost effectiveness

CHANNELS

Sales reps

Distributors

CUSTOMER

SEGMENTS

Vascular surgeons

Patients

Payors(insurance)

REVENUEGrants Sales

COST STRUCTURER&D Overhead

Better cardiac bypass grafts

Revised Canvas 1

PARTNERS

University (UAB)

Material suppliers

GMP Manufacturing

Regulatory / Reimbursement

ACTIVITIES

Animal Data

Human Data

RESOURCES

Biopolymer

HuBiogel

Electrospinning

PROPOSITIO

Minimal immunogenic

Surgery ready

CUSTOMER

RELATIONSHIP

Cost effectiveness

CHANNELS

Sales reps

Distributors

CUSTOMER

SEGMENTS

(Vascular) surgeons

Pediatric surgeons

Patients

Payors(insurance)

Target market: 4 possible segments

Coronary artery disease graftsPediatric congenital disease grafts

Peripheral artery disease graftsHemodialysis (AV) grafts

Revised Canvas 2

PARTNERS

University (UAB)

Material suppliers

Investors

ACTIVITIES

Animal Data

Human Data

RESOURCES

Grants/contracts

Equip. supplies

Consultants

PROPOSITIO

CUSTOMER

RELATIONSHIP

Pub. Agreements

Patient advocacy

CHANNELS

Sales reps

Distributors

CUSTOMER

SEGMENTS

Pediatric surgeons

Patients

Payors(insurance)

New influencers and decision makers:

CardiologistHemodialysis doctors

Revised Canvas 3

PARTNERS

University (UAB)

GMP Compliant CMO

Investors

ACTIVITIES

Animal Data

CE followed by FDA

GLP / GMP

RESOURCES

Grants/contracts

Equip. supplies

Consultants

PROPOSITIO

CUSTOMER

RELATIONSHIP

Pub. Agreements

Patient advocacy

CHANNELS

Distributors

CUSTOMER

SEGMENTS

Pediatric surgeons

Patients

Payors(insurance)

Talked to EU regulatory experts and Updated

canvas

Preclinical milestone: pig carotid dataCE mark in EU (Poland) first

Clinical milestones:restenosis

Peak walking test

Final Canvas

PARTNERS

University (UAB)

GMP Compliant CMO

Investors

ACTIVITIES

Research & Precl. validation

Animal Data

CE before FDA

GLP / GMP

Strategic partners

RESOURCES

Grants/contracts

Equip. / supplies

Know-how

Consultants

PROPOSITIO

Ready-to-use, small diameter (<6mm) vascular graft where there is currently no alternative.

CUSTOMER

RELATIONSHIP

Pub. Agreements

Patient advocacy

Health outcomes / cost effectiveness

CHANNELS

Distributors

CUSTOMER

SEGMENTS

Vascular surgeons

Referring physicians

Hospital P&T Committee

Payors(insurance)

Patients

Re-prioritized markets

1. PAD2. Hemodialysis3. CAD4. Congenital Heart disease

Backup

Slides

Bio-Hybrid Vascular Graft

Unmet Need: Clot-Free Biocompatible Vascular Grafts for Regeneration of Blood Vessels

Value: A clinical solution for patients where autologous graft is not an available option

Unique Design: Natural biomatrix for endothelium (HuBiogel) with biodegradable scaffold for regrowth of vascular tissue

Prototype:

Market

• Total Available Market:– Global vascular interventional devices

market

– Coronary and peripheral endovascular procedures including balloons, stents, grafts, IVC filters, IVUS & angiography catheters, plaque modification devices, hemodynamic flow alteration devices and accessory devices

• Served Available Market:– Coronary Artery Disease - CAD Grafts

– Peripheral Artery Disease - PAD Grafts

– Pediatric Grafts

• Target Market:– CAD, PAD, and pediatric grafts < 6mm

Business Model Canvas

Value Proposition Canvas

- Restore blood flow- Create vascular access- Avoid readmissions- Get higher QALY’s

- improve fistula maturation

- Range of diameter (<6mm)- No clotting- Biocompatible, Reproducible- surgery-ready solutions

- Revision surgeries- Complications- Thrombosis / stenosis- Infections

- 3x less clotting- Minimally immunogenic

- pre-coated, surgery ready

- Unique biogelpromotes

endothelialization- Grows w patient

-- Reduced thrombosis results in lower occlusion, infection, and

graft failure. - Less revision surgeries

- Pre-coated, surgery-ready

- Pediatric grafts- Femoral artery

graft- AV fistula graft

• Freedom to operate/IP?– Possible freedom to operate issue on the utility of combining a

polymer with a biological matrix for a vascular graft. Evaluation underway.

• Clinical Trials/regulatory?– Likely combinatorial product composed of biological and

device. – Likely BLA pathway will be dominant, meaning larger trial than

510k but smaller than PMA– Possible FDA support and HDE exemption tied to pediatric

congenital heart disease with <4,500 cases/year.

• Quality information– Since HuBiogel is a human-derived biological material, there

will be some stringent FDA quality testing requirements (e.g. viral clearance).

– FDA has little experience with setting quality testing standards for BLA products, but biosimilars might create precedent.

Critical Activities

Critical Resources

Resources Associated Activity

Cost Status

Research funding Preclin, validation NIH STTR

IP Preclin, animal, human data

Provisional utility patent filed

Equipment and supplies:polymers and electrospinning

GMP / GLP

Hubiogel Scale-up and manufacture

Commercial grade development underway

CRO Develop strategic partnersDefine endpoints

Partners

Partners Resource / Activity Why Status $

University IP, equipment, grants

Hold IP NIH STTR Phase IProvisional patent

GMP Hubiogel GLP/GMP scale-up & manuf.

FDA regulatory risk

Material sourcing & sale for research →

Regulatory: CRO & FDA Pediatric office

Clinical endpoints & data

Pediatric incentives

IdentifiedSt.Jude’s, FDA contact

Investors Clinical milestones,manufacturing

Cross valley of death

FDA vs CE decision

Clinical opinion leaders

Strategic partnersDefine endpoints

Clinical adoption

Engaged 18 clinicians

Materials Solutions

Regulatory and develop marketing partner

Regulatory starts with material

Extensive dialog with Evonik ↔

Marketing Partner

Scale up and sales Sales &distribution

Identified most likely partners

Preclinical Studies

tissue procurement/ processing

CROAdvocacy,

Clin. Partner

Strategic Marketing

Partner

Activities and resources

Preclinical Studies

GLP / GMP Mf

Animal Data

Human Data

Marketing

Activities

Resources / partners

UAB / S. Research

Baxter SKIRBALLCRF, AHA

St.Jude’sShire

Pharma

Possible partners

Channels

• Distribution:– Strategic marketing partnership

• Abbott

• Cook

• Covidien (Medtronic)

– Alternatives• Independent Distributors

• Direct sales through hospital pilot programs derived from clinical trial champions

– Channel partner interest• Key inflection point: human data

• Several recent companies acquired at human clinical data stage

Channel Diagram

Preclinical Studies

GLP / GMP Mf

Animal Data

Human Data

Marketing

Strategic Marketing partner license

X% royalty

Champions from clinical trials

Targeted hospital

population management

(pilot)

Direct sales

Customer Workflow

Vascular surgeon

Nephrologist,Internist,

Neonatologist,Cardiologist.

Provider

Graft companies

Technology committee?

Payment

• Bundled Payments

1. Coronary Artery Bypass Grafting: $39,572

2. Peripheral vascular disease graft: $5,812

• Graft Payments

- Arterial: $1,000-$2,000

Procedure Code Reimbursement

Payment flows

Physician servicesER physiciancardiologist,

Internal medicine/primary care

inpatient

Graft companies

Payor(CMS)

Hospital svcs

outpatient

DiagnosticsAlternative / complement procedures

CABG $39,572PVD $5,812

$3,845

$33,067

Anesthesia$2,660

<$89 – $1,000

Finance timeline

2010 $12M

2012 $10M

2014 $37.25M

Humacyte referenceBackground: - RTP, technology licensed from Duke & MIT.- Tissue-based vascular grafts and regenerative medicine products

011 Data published

in Science Transitional Medicine

012 multi-center,

first-in-human pilot study starts in Poland A

13 Three-month CE safety review complete

FDA IND approval for ESRD

013 Strategic

ManufacturingpartnershipAllosource

Clinial trial enrollment complete:- 40 patients EU - 20 patients US (3 sites each)

FDA Fast Trackapproval

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