Chronic TOTB @ Chronic TOTB @ OrthopeuticsOrthopeuticsChronic TOTB @ Chronic TOTB @ OrthopeuticsOrthopeutics

Tom Hedman, Ph.D.Tom Hedman, Ph.D.A i t R h P fAssociate Research ProfessorDepartment of Neurosurgery and Center for Biomedical EngineeringUniversity of Kentucky

Founder, General Partner and Chief Scientific Officer, Orthopeutics, LPFounder, Equinext, LLCFounder, Chairman, Intralink Spine, Inc.

Clinically Driven InnovationClinically Driven Innovation& k

Clinical Needs• Spinal disc degeneration & LBP

Necessity, who is the mother of invention.l h bl (

DDD & Low Back Pain:•3rd most common reason for surgery

NEXT generation

Plato, The Republic (427 BC –347 BC)•9.4% of US population (diabetes 5.9%, heart disease 8.1%, cancer 0 5%)We are surrounded by engineers' follies: too 

t h i l

0.5%)

•Most costly ailment for working age adults, $100B+/yr. in US

many technical solutions still looking for problems to solve

•>15 million/year in US receiving treatment

•For every surgical patient there is 

First generationPerformance Enhancement vs. Replacement

for problems to solve.David Tansley>20 back pain sufferers receiving treatment from a clinician

NEXTNEXT ‐ Nonsurgical  EXogenous Crosslink Therapy

• Injectable Collagen Crosslink augmentation

• Genipin‐based reagent augments crosslinking of native ECM

• Injectable/conservative care/ biomimetic approach

/• Immediate effect/ long‐lasting covalent bonds

• Cost effective

genipinNEXTTM

genipin

Increasing Crosslinking of Native Tissues Increasing Crosslinking of Native Tissues --Flies in the Face of Conventional Wisdom: Flies in the Face of Conventional Wisdom:

Age-increasing crosslinking “… the major cause of dysfunction of collagenous tissues” – Bailey ‘98

Wh did th ?Why did we go there?1. No data to support strong literature bias – repeated claims of increased

brittleness, loss of fatigue resistance with no biomechanical datag2. Duance3. HC-UHMWPE

Why not inject a biologic agent Why not inject a biologic agent (the ‘mainstream’(the ‘mainstream’ aproachaproach)?)?(the  mainstream  (the  mainstream  aproachaproach)?)?

x Harsh, nutritionally deficient environment of the avascular disc Intervertebral Discenvironment of the avascular disc led to degeneration in the first place

x “Degenerative discs are not able to support the added nutrient demands

Intervertebral Disc(largely avascular)

support the added nutrient demands from increase in cellular activity or cell number…”

x Biological treatments offer no nearVertebral Body(well vascularized)x Biological treatments offer no near-

term effect, not appropriate as a stand-alone treatment

x More challenging regulatory path

(well vascularized)

x More challenging regulatory pathx More expensive to produce

Translational Translational RResearch esearch AAimsims

UF

Increase retention of GAGs/ hydration?Increase nutritional flow/ permeability?Improve mechanical properties/ durability?

Underlyingactors

Improve mechanical properties/ durability?Reduce disc bulge?Reduce joint instability?

gPainGenerj y

Increase tear resistance?Provide adhesion of adjacent tissues?E i i l t i it ?

rators    

Ensure minimal toxicity?Useful as an adjunct to surgery?Fast-acting / Long-lasting?

Other

Criteria    Fast acting / Long lasting?Inexpensive?

     

Summary of Experimental Results: NEXT…Summary of Experimental Results: NEXT…

UF

Increases retention of GAGs/ hydration (>40%) Increases nutritional flow/ permeability (100%) I h i l ti / d bilit ( 25%)

Underlying

Factors

Improves mechanical properties/ durability (>25%) Reduces disc bulge (>25%) Reduces joint instability (4-fold)

gPainGeneReduces joint instability (4 fold)

Increases tear resistance (50%) Provides adhesion of adjacent tissues (3X)

rators    

Exhibits minimal toxicity A good adjunct: Restabilizes post-discectomy Fast-acting / Long-lasting

Other

Criteria    Fast-acting / Long-lasting Inexpensive (90% reduction in device costs)

      

NEXTNEXT Is the Perfect Adjunct to Is the Perfect Adjunct to CellCell‐‐Based TherapiesBased Therapies

Provides immediate joint stability and resistance to mechanical degradationmechanical degradation

Crosslinking increases nutrient permeability to enhance long-term treatment viability

Technology Driven Innovation Technology Driven Innovation ––TOTB for Other ApplicationsTOTB for Other Applications

Clinical Applications In Common• Spinal disc degeneration• Spinal deformity• Knee meniscus tears

• Mechanical insufficiency• Demanding repetitive

loading• Tendon and ligament

stabilization in the extremely non-compliant patient

• Nutritional deficiency• Inadequate regeneration• High to extremely highp p

(equus ferus caballus)• Snoring & obstructive sleep

apnea

High to extremely high prevalence

• Absence of effective repairs or treatments

• Spinal elongation in 0g• …

or treatments

Technology Driven Innovation Technology Driven Innovation ––

Gave/Giving Birth To:Clinical Applications• Spinal disc degeneration• Spinal deformity• Knee meniscus tears• Tendon and ligament

stabilization in the extremely non-compliant patient p p(equus ferus caballus)

• Snoring & obstructive sleep apnea

• Spinal elongation in 0g• …

Will All of These Be Successful?Will All of These Be Successful?"I have not failed once. I've just found 10,000 ways that didn't work." --Thomas Edison"The way to succeed is to double yourThe way to succeed is to double your failure rate.“ -- Thomas Watson, Founder of IBM"Failure is only the opportunity to b i i i t lli tl “begin again more intelligently.“ --Henry Ford"We are not retreating -- we are advancing in another direction.“ --gDouglas MacArthur"Never confuse a single defeat with a final defeat.“ -- F. Scott Fitzgerald"Fall seven times stand up eight "Fall seven times, stand up eight. --Japanese Proverb

Sources of Funding

Kentucky SBIR Matching Grant NIH-NIAMS SBIR Grant R44 AR55014-02A1NIH-NIAMS SBIR Grant R43 AR55014-01A1NIH-NIAMS STTR Grant R41 AR47470-01A1University of Kentucky College of EngineeringUniversity of Kentucky College of Medicine University of Southern California (Royalties-TPH)Orthopeutics (Equity ownership-TPH)Equinext (Equity ownership-TPH)

(Financial disclosures)

Thank You!

U S D t t f H lth

Thank You!

U.S. Department of Health and Human Services

Supported By

National Institutes of Health

National Institute of Arthritis and Musculoskeletal and Skin Diseases