GreenBone

The Hague (NL) March 31, 2016 Most Inspiring Idea from Europe

GreenBone has different applications

Non-union – pseudarthrosis

fractures

Cancer (i.e. sarcoma)

Infections(i.e Osteomyelitis)

Spine fusionBone augmentation

Leg length discrpancy

v  Initial focus is non-union – pseudarthrosis fractures.

Patients are waiting for our solution

Ø  Bone grafting is a common surgical procedure. Ø  More than 4 million reconstructive grafting procedures each year. Ø  No effective solutions today for critical size defect.

Bones and rattan (bamboo related tree) are similar

CONFIDENTIAL+

14""

Figure 5. Process of transformation of natural woods into hierarchically structured

hydroxyapatite.

Figure 6. Scheme of the sequence of intermediate and final products obtained by the

transformation process

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" The best material for bone regeneration

CompleteBoneregenera.on

HA Scaffold

Rattan

v  Completely transformed in HYDROXYAPATITE

v  No sintering: nano-size crystals

v  Bio-mimetic

GreenBone is really unique and low risk

q  Medical device q  Bone formation & load

bearing demonstrated in-vitro and in animals

q  Easy to shape for various applications

q  Manufacturing process scaled-up

GREENBONE Pg. 2 of 30

1 Excellence 1.1 Project Objectives

Project Objectives Related deliverables

1 The primary goal of GreenBone is to develop a highly innovative bone implants technology, to generate biomimetic – reabsorbable – wood-derived scaffold with mechanical performance adequate to address non-union fractures that result in extensive (3-5 cm) bone loss. Bone regeneration in large bone defects is an important and unsolved problem in trauma and orthopaedic practice with high economic impact on healthcare system and serious social costs. Indicators of success: At the end of the project GreenBone will demonstrate effectiveness-regeneration of 3-5 cm bone critical size defect caused by trauma in long bones.

D1.1, D1.2, 1.3, D1.4

2 A scaled-up manufacturing line will be optimised and validated accordingly with Good Manufacturing Process (GMP). Starting from scaffolds with an average length of 3-5 cm, the line will be implemented to manufacture scaffolds up to 7 cm long, a dimension suitable to provide bone-grafting samples for the very large majority of critical size defects clinical applications, and reach the maximum theoretical yelds. Indicators of success: The manufacturing optimisation will target production scraps reduction from 20-30% to 10-15%. Production yield will increase up to 90% with a full capacity of 220 scaffolds each month, about 2200 scaffolds a year.

D2.1, D2.2

3 A First-in-man study will be performed on more than 30 patients with diaphysial bone loss between 3-5 cm in the upper and lower limbs caused by trauma, non-union and pseudo-arthrosis. 4-5 clinical centres will participate to the study. Scaffolds will be implanted with or without bone marrow extract and fixed accordingly with standard procedures. In particular, bone loss in long bone will be considered (humerus, ulna, radius, femur, tibia and fibula). Indicators of success: bone recovery, bone regeneration quality and scaffold reabsorption will be demonstrated. All patients will be subject to the complete follow-up (i.e. clinical observation, X-ray, CT and MRI to assess safety, clinical surgery remission and bone graft consolidation) until 24 months after surgery.

D3.1, D3.2, D3.3

4 The GMP validated line will be improved in terms of manufacturing yield to achieve high economical sustainability. These will also strength company attractiveness towards major industrial players. This will allow commercial partnerships boosting worldwide penetration of GreenBone scaffolds and supporting further development to achieve other skeletal districts (i.e. spinal area), and pathologies such as bone cancer resection and certain orphan diseases causing bone loss/lack of bone functionality. Indicators of success: manufacturing yield >80%. With an expected price between 2,000 and 3,500€ for each scaffold accordingly with dimension, GreenBone will reach a total turnover of 4 million euro in the next 4 years

D4.1, D4.2, D4.3

1.1.1 Industrial economical/societal problems to overcome and the business opportunity Bone defects are very challenging in orthopaedic practice since they can result from malformation, high-energy traumatic events, bone resection due to different pathologies such as tumour or infection, or from the treatment of complex non-unions (i.e fractures which do not consolidate within a period between 6 and 8 months). Bone healing differs from any other soft tissue since it heals through the generation of new bone rather than by forming fibrotic tissue. Current therapy of bone defects (BDs) usually implies the use of bone grafts and/or biomaterials, to create a scaffold that bridges the defect, favouring the migration of cells from the neighbouring tissues to fill the gap. Bone grafting encompasses more than 10% of all skeletal reconstructive surgery cases. Worldwide, 2-3 million grafting procedures are estimated each year. Autograft, allograft and synthetic bone graft substitutes and bioactive glasses are

the treatments currently used, however, no effective solutions are available today to cure severe conditions that result in critical bone loss such as trauma, tumours and bone infections. Depending on the skeletal segment involved, a defect can be considered critical in relation to the length of bone loss: 3 cm for the forearm, 5 cm in the femur and tibia, 6 cm in the humerus.

GreenBone at a glance

ü  World class 7 people team (business, R&D, manufacturing, RA&QA) that has advanced multiple orthopaedic products from bench-to-market.

ü  Collaboration with Rizzoli Orthopaedic Research Institute (Bologna, Italy).

ü  Patented.

ü  Seed Round 3.0M EURO 1Q 2015

Innovative wood-derived bone regenerative

load bearing grafts.

CONFIDENTIAL

²  TEDxBinnenhof 2016 ‘Ideas from Europe’ March 31, The Hague (NL)

²  Biomed Tel Aviv 2015 "WOW Factor" Start up Finalist

²  “Smart & Disruptive Company – Italy 2014” by MIT Review.

²  “30th among top 50th researches worldwide” by Time Magazine 2010.

GreenBone

Lorenzo Pradella, Co-Founder & CEO lorenzo.pradella@greenbone.it