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Gistograft IR
1. Large and quick bone growth with gene-activated materials
WITHOUT additional methods, costs and time wasting
Moscow, 2018
Histograft
2. Sections Slides
About company 3
Resume 4
Problem 5-7
Proposed solution 8, 9
Market and business model 10-16
Products 17
Competitive landscape, advantages 18-20
Currents status 21, 22
Intellectual properties 23
Milestones 24
Financial indicators 25, 26
Risks 27, 28
Team 29, 30
ContentHistograft
3. 20%
80%
Ilya Bozo Roman Deev
Authorised Capital
About company
• Founded in 2015 for development and clinical
translation of the new class of medical devices –
gene-activated materials
• Resident of the Skolkovo Foundation
• The project was supported by Foundation for
Assistance to Small Innovative Enterprises in
Science and Technology (Start-1)
• Co-investor: Artur Isaev
• Parthners: IMMS of RAS (Vladimir Komlev), K(Vr)SU
(Andrey Kiyasov), MSUMD (Alexey Drobyshev),
University of Leeds (Georg Feichtinger).
Histograft
4. Resume
1. The main problem in bone grafting – poor bone growth that could be achieved with
the most of approved bone grafts and substitutes
2. Company’s products – gene-activated materials – are able to solve this problem
because of stimulatory effect on bone regeneration produced by plasmid DNA
encoding VEGFA gene. It is going to achieve the planned market coverage at 10% and
company value growth
3. Market volume: 394,7 thou. patients annually, 295,3 thou. items in stomatological
segment and 140 thou. – in traumatology and orthopedics
4. The main products: gene-activated materials in the forms of granules, membrane,
personalized blocks (produced with 3D-printing technologies)
5. Technologies are patented, project team has been formed
6. NPV 40,9 mln., IRR 42%
7. Financial recourses demand and conditions: 7 mln. for 10% of company; 6x multiples
in 6 years.
Histograft
5. Problem
• 400 thou. patients with bone defects and alveolar ridge atrophy in Russia
annually need bone grafting – a surgery with bone substitute implantation
• Bone substitute’s task – to provide a bone tissue growth
100% bone growth is UNREACHABLE still
Vgrafted materials = V newly formed bone tissue
• Approved bone substitutes facilitate just 1-2
mm bone growth from bone defect walls
• The rest of bone substitute produce just
connective tissue, does not form a bone
Histograft
6. Problem
The main bone grafting problem – insufficient bone growth
Key market’s problem
Physicians do not have a material with osteoinduction capable
to stimulate the regeneration of the patient's own bone tissue
physicians are compelled to mix the
materials with autobone fragments,
platelet-rich plasma, etc.
Increase of surgery time, risk of
complications, cost
Bone regeneration
time are
too long
long waiting for the
treatment result
high frequency of
additional bone
grafting
duration of treatment,
increased incidence of
complications, costs and
reputational risks
Histograft
7. Bone tissue growth
Histograft increases bone tissue growth
It is demanded by physicians and will allow them
• to place dental implants of optimal length and diameter
• to place dental implants in a shorter time after bone grafting
• to avoid the use of autologous tissue, PRP, PRGF, etc.
• to minimize the frequency of repeated surgeries
• to take on challenging clinical cases they was compelled to be rid of earlier
• to increase profits by reducing the production cost of surgical treatment
Histograft will help physicians
To achieve larger and quicker bone growth with gene-activated materials
WITHOUT additional methods, costs and time wasting
Histograft
8. Proposed solution
Gene-activated material
A new class of medical devices consisting of a
bioresorbable scaffold and biologically active nucleic acids
(gene constructs) carrying a growth factor gene
Mechanism of action:
• Scaffold fills the defect of tissue/organ, guides the
newly formed tissues, being replaced them
completely – conducted effect
• Gene constructs are released from the scaffold,
enter cells and enhance the production of a
therapeutic protein stimulated regeneration –
inductive effect
Histograft
10. Russian market
Skeletal bone pathology
Annual number of bone grafting/ patients in the Russian Federation:
• Bone grafting for dental implants placement – 171,3 thou.
• Bone grafting in traumas surgeries – 50 thou.
• Spinal fusion – 30 thou.
• Revision endoprosthetic arthroplasty of joints– 8 thou.
• Osteomyelitis and osteonecrosis – 63,6 thou.
• Bone resection because of malignant tumors – 5,8 thou.
• Benign tumors and cysts – 15,6 thou.
• Post-traumatic deformities, delayed and non-unions– 45,3 thou.
• Congenital deformities and developmental anomalies – 5,1 thou.
394,7 thou.
surgeries with bone grafting
Histograft
11. Russian market
Segment capacity
• Dental (bone grafting for dental implants placement, periimplantitis, periodontitis, jaw cysts, etc.) *
95,4
191,3 184,6
57,2
114,8 110,7
0
50
100
150
200
250
2015 2016 2017
Numberofitems,тthou.units
In-kind value
в виде гранул в виде мембран
477
956,5 923
400,4
803,6 774,9
0
200
400
600
800
1000
1200
2015 2016 2017
ml.rubles
Monetary value
в виде гранул в виде мембран
• Traumatology-orthopedic and maxillofacial segments of the market – 140 thou. units of products in the
form of granules (700 mln. rubles), but the potential volume – 739.7 thou. units (3.7 bill. rubles).
*Based on the data of the Straumann Group (Switzerland) annual reports
Planned occupation of 10-12% of the market in dental segment
Histograft
granules membranes membranesgranules
12. Business model
Contract production of
gene-activated bone
substitutes
м
B2B
Dental clinics, departments of maxillofacial
surgery, traumatology and orthopedics
(private and public)
B2С
• Physicians
Patients (as directed by a physicians)
Direct sales and sales through distributors (with 25%
discount)
- master classes
- clinical guidelines
- industry exhibitions and
scientific conferences
- interaction with network
clinics
- calls / visits of clinics by
sales representatives
- tenders / government
purchases
Histograft
13. Dental segment of the market
Customers
1. Dental clinics – 28,6 thou.*
Of these, private – 25,7 thou.
Of these:
- Moscow – 1731
- Saint-Petersburg – 1352
*based on BusinesStat data for 2015
2. Physicians (oral and maxillofacial surgeons) –
7,6 thou.*
*based on RusStat data for 2012
1. Price and terms of sale
2. Personal interest of the chief (forms an
application)
3. Product quality
4. Opinion of physicians about the product
Motives for decision-making
1. Opinion about the product (personal and
colleagues’)
2. Product quality
3. Price and terms of sale
4. Personal interest
Ways to stimulate sales
• Flexible system of discounts, deferred payments in dealing with clinics
• Providing free samples to new clients for primary use
• Involving opinion leaders to promote project products
• Quality service (convenient ordering options, fast delivery, return / exchange)
• Continuous accumulation and analysis of the results of the products use, active informing of physicians
• Gifts for physicians for certain volumes of orders for reporting periods
• Personal conditions for the heads of clinics
Histograft
14. Market access
1. Sales through distributors: contracts with the main trading companies in the field of
dental materials (Stomatorg, El Dent, Medent, etc.)
2. Organization of post-marketing clinical studies (Moscow, Moscow region, St.
Petersburg, Novosibirsk, Krasnodar) involving opinion leaders
3. Organization of company’s own direct sales channels in the B2B segment: the
largest clinics in Moscow -> Moscow region -> St. Petersburg and Leningrad region -
> regions
4. Organization of company’s own sales channels in the B2C segment: formation of
physicians and clinics databases, personal management and involvement
The key to increase market coverage is accumulation and systematization of
clinical data with active informing of consumers through opinion leaders about
long-term outcomes
Histograft
15. Dental segment of the market
20 dental surgeons were interviewed
"Yes"
40%
"Yes" with
conditions
25%
"No"
35%
Interview results
- "YES" with declared characteristics / advantages –
8
- "YES under certain conditions": 3-5 thou. rubles
per gram, reliable comparative results with bio-oss,
availability of clinical data – 5
- "No" - 7 (distrust of domestic materials, skepticism,
loyalty to bio-oss and bone autografts)
The main question:
Would you buy the gene-activated bone
substitute "Histograf"?
Histograft
16. Dental segment of the market
Participants
• About 100 of medical products (99% ordinary - do not contain biologically active components that
can induce osteogenesis)
• Only 1 product with a biologically active component (Embogain®, Straumann) for a minor
indication in periodontology
• The market leader (35% in monetary terms) is Giestlich Biomaterials (Switzerland) with the
product line "Bio-oss" (granules, standardized blocks) and "Bio-guide" (membranes); the exclusive
distributor – "SIMCO".
• The average cost of products in the form of granules (per 1.0 g)
- The market leader – 11 000 rubles
- other foreign products (55% of market) – 8 000 rubles
- Russian products (10% of market) – 3 000 rubles.
• The average cost of products in the form of membranes
- foreign products – 8000 rubles
- Russian products – 3000 rubles
Histograft
17. Project products
Bone substitute «Histograft»
• Granules of octacalcium phosphate and plasmid DNA carrying gene of vascular
endothelial growth factor
• Granules size: 50-150, 150-500, 500-1000, 1000-2000 µm. Weight in flask: 0,5; 1; 2;
5 g.
• For use within existing indications on the market
Personalized implants of gene-activated material
• The composition is similar to "Histografte“ bone substitute
• Fabrication with 3D printing technology for each patient
• No registration required as a medical device in Russia
• Expansion of the existing market due to efficiency in cases bone autografts are used
so far
Gene-activated membrane
• A collagen or other membrane containing plasmid DNA carrying VEGF gene
• Different size and thickness
• For use within existing indications on the market in combination with "Histografte“
bone substitute
Gene-activated gel
• Injectable scaffold with an optimized plasmid DNA carrying a therapeutic gene
• Not only for bone grafting but for skin regeneration as well
The project products do not only cover current indications but are able to expand the market
Histograft
18. Competitive analysis
Competitor groups / advantages
I. Bone substitutes in granular and membrane forms
• Competitor 1 - Giestlich products - xenogenic materials from deproteinized bone matrix and collagen,
harvested from New Zealand cows. More than 20 years of clinical experience, high price, the largest
number of scientific publications in different countries, the most famous and recognizable brand, high
osteoconductive properties, minimal osteoinduction, optimal packaging
• Group of competitors 2 - other foreign products - materials based on calcium phosphates,
hydroxyapatite, xenogeneic bone matrix. Do not contain biologically active components, therefore do
not have osteoinduction, but possess pronounced osteoconductive properties, middle price, optimal
packaging
• Group of competitors 3 – Russian products - low efficiency, lack of strong brands, low quality of
packaging, low price
• Competitor 4 (potential) is a foreign product containing biologically active components: growth
factors or proteins. They have not been registered in Russia yet. They are characterized by extremely
high cost, the efficiency is higher than materials without biologically active components
Advantages of the
project products
• High osteoinduction – ability to induce bone regeneration
• Innovation - a new class of medical products
• high efficiency (osteoinductive action of gene constructs +
osteoconductive action of the scaffold)
• competitive price (middle)
Histograft
19. Competitive analysis
Competitor groups / advantages
II. Bone substitutes in the block form
• Group of competitors 1 - bone autografts - “a gold standard" for bone grafting. Optimal
biocompatibility, high efficiency, but require the highest degree of surgeon qualification, extend a
surgery time for 1-2 hours, often can not be used in outpatient settings; risk of additional
complications caused by additional trauma
• Group of competitors 2 - standardized blocks of bone substitutes (Giestlich and analogues,
allogeneic bone materials). They do not differ in efficiency from granulated products, do not
provide reliable fixation in the bone defect site, do not contain biologically active components
capable to induce osteogenesis
• Group of competitors 3 – individually made implants from non-resorbable materials
(polymethylmethacrylate, titanium) – are used as a "last hope" when other methods for bone
reconstruction can not be used
• Exact match in shape and size to the replaced bone defect
(personalization)
• High osteoinduction – ability to induce bone regeneration
• Innovation - a new class of medical products
• high efficiency (osteoinductive action of gene constructs +
osteoconductive action of the scaffold)
• Stable fixation
Histograft
Advantages of the
project products
20. Competitive analysis
Comparison with the main competitors
Comparison
criteria
Histograft Bio-oss Endobon Tricafor Infuse
Composition OCP+plasmid DNA
with VEGFA
Deproteinized
xenogenic bone
matrix
Deproteinized
xenogenic bone
matrix
β-TCP Collagen sponge
+ rhBMP-2
Ability to guide
bone regenerate
+++ +++ ++ ++ +
Osteoinduction +++ + - - ++
Price for 1.0 g,
rubles.
7 500 11 000 8 500 2 500 About 56 000
Biodegradation
time
8-9 mo. 8-9 mo. 8-9 mo. 10-12 mo. 1-2 mo.
Quality of
packaging
+++ +++ +++ + +++
Brand loyalty N/a +++ + - ++
Histograft
21. Current status
Gene-activated materials platform
✓ Original technology for creating gene-activated materials, including personalized, made of solid
scaffold and plasmid DNA carrying a therapeutic gene
✓ 3D-printing technology of calcium phosphates scaffolds
✓ Fundamental principles technologies for development, safety and efficacy evaluation of the gene-
activated materials
✓ Pre-clinical studies have shown the effectiveness of gene-activated materials in various tissues
regeneration
✓ Technological procedure for production of sterile gene-activated bone substitutes consisting of a
solid scaffold and gene constructs
✓ Strong IP protection
✓ Project team includes highly qualified specialists, co-executors with the required level of resources,
as well as experience for carrying out assigned tasks
✓ Received a financial support from Foundation for Assistance to Small Innovative Enterprises in
Science and Technology (Start-1)
Histograft
23. Intellectual property
• Bozo I.Y., Deev R.V., Komlev V.S., Isaev A.A. A method for producing an optimized solid gene-
activated material, a method for preparing a solid carrier matrix, an optimized gene-activated
material for tissue regeneration. Priority Date: 10/07/2016. RU Patent No. 2623171 of June 22,
2017. Assignee: Histograf LLC.
• Isaev A.A., Kiselev S.L., Deev R.V., Boso I.Y., Filonenko E.S. Biocomposite for providing recovery
processes after damage in a mammal, the method of its preparation (variants) and applications.
Priority Date: 12/29/2011. RU Patent No. 2519326 of 14/04/2014, Ukraine Patent No. 112,450 of
12 September 2016, EU Patent No. 2797633 of November 30, 2013, US Patent No. US 9,730,959
B1 of August 15, 2017. Assignee: PJSC “HSCI “
• Boso I.Y., Komlev V.S., Drobyshev A.Y., Isaev A.A., Deev R.V. The method for creating a personalized
gene-activated implant for the regeneration of bone tissue. Priority date: 10/02/2015. RU Patent
No. 2597786 of August 24, 2016. Assignee: PJSC “HSCI “
Patents
Know-How
• Technological regulations for the production of two-phased gene-activated bone substitutes
Histograft
24. Milestones
The main project stages within 2018-2019
Milestones 2018 2019
“Histograft” bone substitute registration in Russia
Start of sales
Optimization of personalized gene-activated implants
technology
Development of a prototype for gene-activated gel
Development of a prototype for gene-activated
membrane
Personalized gene-activated implants clinical trial
Preclinical studies of gene-activated gel and membrane
Histograft
27. Risks
Type of risk Description Significance Probability Methods of reducing
Technological inability to create gene-
activated materials with the
required dose of gene
constructs
High Low performed preclinical studies allowed to
minimize the risk; we developed technologies
allowing to specify the exact dose of gene
constructs in the solid scaffold
a low level of biologically
active nucleic acids delivery
from the scaffold structure
to the tissues of recipient
site after implantation
High Middle use of additional technologies capable to
increase the transfection efficiency
insufficient duration or level
expression of therapeutic
gene(s) encoded by
biologically active nucleic
acids
High Middle - use of technologies prolonging a release of
gene constructs from the scaffold
- use of gene constructs in high doses
impossibility of gene-
activated bone substitutes
manufacturing in a sterile
form
High Middle application of the developed three-staged
manufacturing scheme
Histograft
28. Risks
Type of risk Description Significance Probability Methods of reducing
Industrial Registration of other products
with biologically active
components (cells, growth
factors, gene constructs)
High Middle The first material on the market with
biologically active components and wide
indications for use will have a priority
Commercial Impossibility to overcome the
adherence of customers to
accustomed products
High Middle - correct and one-stage impact on the main
decision-making motives of each categories of
consumers will ensure the target market
coverage
- unique advantages of the project products
providing greater efficiency
Financial Currency, additional costs for
the order of consumables
required for the project
Middle Low constant monitoring of the consumables and
equipment cost, including those planned to be
purchased at subsequent stages of the project
for prompt decision-making on procurement at
an earlier time
Regulatory changes in registration
process and regulated
documents for implantable
medical products with
biologically active
components
Middle Middle - constant monitoring of changes in regulatory
documents
- prompt change of the acquisition plan and
correction of registration dossier in accordance
with the new requirements
Histograft
29. Project team
Ilya Bozo
MD, PhD, a maxillofacial surgeon,
executive editor of the Journal «Genes &
Cells»
Role: Project head
Experience: co-founder and CEO of
Histograft LLC, a developer and inventor
of gene-activated bone substitutes,
organizer of preclinical and clinical trials
of the first product
MD, PhD, a histologist, pathologist,
chief editor of the Journal “Genes &
Cells”
Role: Chief Researcher
Experience: co-founder and CEO of
Histograft LLC, a developer and
inventor of gene-activated bone
substitutes, organizer of gene-
therapeutic drug “Neovasculgen”
post-marketing studies
Roman Deev
Key members Partners
Co-investor
Experience: founder and CEO of
PJSC “HSCI", the winner of the
international competition
"Entrepreneur of the Year
2012" in Russia in the
nomination "High
Technologies" conducted by
Ernst & Young.
Artur Isaev
Vladimir Komlev
PhD, DSс, corresponding
member of the RAS
Role: scientific consultant
Experience: Director of the
IMMS of the RAS, a developer
of bone substitutes based on
calcium phosphates, a
laureate of the Presidential
Prize for young scientists in
science and technology
Histograft
30. Project team
Experience and achievements
1. Participation in development and commercialization of the first-in-class gene-
therapeutic drug "Neovasculgen" for treatment of patients with chronic lower
limb ischemia (included in the List of vital essential and necessary drugs)
2. Achievement of the scientific journal "Genes & Cells" (included in the list of HAC,
indexed in Scopus) commercial effectiveness through the establishment of the
special company and proper organization of business processes
3. Obtaining of financial support from Foundation for Assistance to Small Innovative
Enterprises in Science and Technology (Start-1)
Histograft
