Biotec’s Soluble Beta-Glucan (SBG ® ) in clinical applications and its scientific platform Arctic Biotech Seminar 30 th November 2015 CSO Rolf E Engstad
Biotec’s Soluble Beta-Glucan (SBG®) in clinical applications and its scientific platform
Arctic Biotech Seminar 30th November 2015
CSO Rolf E Engstad
Agenda
• Company
• Soluble beta-glucan (SBG®) as PAMP
• SBG as platform for immunotherapeutic applications
• Healing of stalled wounds
• Immunotherapy of cancer
• Summary
Biotec Pharmacon ASA 2
Biotec Pharmacon
• Company
• Established 1990
• Listed on OSE ticker: biotec
• About 35 employees
• Two operating subsidiaries:
• Biotec Beta-Glucans AS & ArcticZymes AS
• GMP, ISO-13485, and ISO 9001
Biotec Pharmacon ASA 3
• Beta-Glucans
• Development, production and sales of beta-
glucans since 1990
• Proprietary and patented manufacturing
processes
• Product range from feed grade (M-Glucan®)
to pharmaceutical grade (SBG®)
• GMP approved plant in Tromsø
One source – different products
Yeast cell walls from
yeast extract
production
(25% BG)
M-Glucan™
Feed ingredient
(65% BG)
BG Particulate
Nutrition
(80% BG)
BG Cos
Cosmetics
(90% BG)
SBG™
Soluble Beta-Glucan
(Medicinal product)
(99% BG)
Molecule optimized
Biotec Pharmacon ASA 4
Innate immunity – how is it triggered?
• The innate immune cells (especially macrophages) has through evolution
developed strategies to eliminate pathogenic microbes by recognising
conserved structural elements on the surface of each group of
pathogens
• These conserved structural elements on microbes are referred to as
PAMPS- «Pathogen Associated Molecular Patterns», and where Beta-
glucan represents yeast, fungi and a few bacterial species
• Each PAMP triggers a specific set of reactions in macrophages through
selective binding to surface receptors
• «Training of macrophages by beta-glucan» Saeed et al. Science 2014
Biotec Pharmacon ASA 5
Metchnikoff Elia (1887). "Sur la
lutte des cellules de l’organisme
contre l’invasion des microbes-
On fighting cells of the body
against invading microbes. Ann.
Inst. Pasteur 1: 32
Biotec SBG trigger innate immune responses
• Biotec SBG is tailored for optimal binding to white blood cells of the
innate immune system, especially the macrophages triggering
controlled production of:
• Production of signal molecules alerting the immune system
• Production of growth factors supporting cell growth
• Increased bacterial killing
• Increased antigen presentation
• Biotec SBG induces a safe and well regulated response
Ideal candidate for many immunotherapeutic applications
Biotec Pharmacon ASA 6
Uniqueness of SBG®
• The Biotec SBG molecule is tailored to trigger a well regulated innate immune
response different from other PAMPs and adjuvants that often have side effects.
• The SBG having very distinct rheological (gel forming) properties
• SBG is patent protected by a number of patent families covering production,
formulation and application
Biotec Pharmacon ASA 7
CH2OH O
OH
O
OH
O
CH2OH O
OH
OH O
OH CH2OH O
OH
O
OH
CH2OH
O
OH O
OH
CH2OH O
OH
OO
OH
CH2OH O
OH
OH O
OHCH
2OH O
OH
O
OHCH
2OH
O
OH O
OH
CH2 O
OH
O
OHCH
2OH O
OH
O
OHCH
2OH O
OH
O
OHCH
2O
OH
O
OHCH
2OH O
OH
O
OHCH
2OH O
OH
OH
n
n
n
Soluble Beta-GlucanHealing of stalled woundsAdvanced wound care
Regulatory approval of Woulgan®
• Strategic decision to apply for a Medical Device registration of Woulgan ®
• Woulgan ® is approved in the most advanced medical device category in Europe
• Biotec’s SBG® is approved as a medicinal substance in Woulgan ®
• Woulgan ® is approved for use in chronic wounds , burns, surgical wounds as well as
for more «everyday» wounds
• Approved main functional claims:
• moist wound healing properties
• activation of macrophages
Biotec Pharmacon ASA 9
Status and strategy for clinical development
• What we have:
• Existing Randomised Clinical Trial (double blinded placebo controlled)
• Surveys in Norway, UK and Germany
• A comprehensive documentation on mode of action, animal studies etc.
• What we need:
• Post Market Clinical Follow-Up ( ongoing)
• Case study series for local KOL support
• Potential clinical studies to get regulatory approval outside Europe
Biotec Pharmacon ASA 10
SBG® in wound care – mode of action
• SBG® activates macrophages
to produce signal molecules
and growth factors resulting in:
• Wound contraction
• Cell proliferation
• Angiogenesis
Increased healing
(ref.: Skjæveland & Engstad 2013)
Biotec Pharmacon ASA 11
-10
40
90
0 4 8 12 16 20 24
% C
on
tra
cti
on
0
5
10
15
20
25
30
35
Marginal Intermediate Centre
Pro
life
rati
ng
cell
co
un
t(f
ov)
0
20
40
60
80
100
120
140
160
Marginal Intermediate Centre
An
gio
ge
nsis
Co
un
t (f
ov)
Water Woulgan Biogel «Woulgan Biogel» without SBG
Cell proliferation Angiogenesis
Wound contraction
0
10
20
30
40
50
60
0 1 2 3 4 5 6 7 8 9 10 11 12
Duration of therapy (weeks)
Patients with complete healing (%)
SBG® in Diabetic Foot Ulcer – clinical data
Biotec Pharmacon ASA 12
SBG
Control
Placebo controlled double blinded study of 60 patients
Statistical significant after 8 weeks (p=0.03)
• Methylcellulose (Placebo control)
• N= 60
• Treatment schedule:• 3 treatments per week
• Up to 12 weeks treatment
• Ulcer size 1-34 cm2
• Complete healing (PP):
8 weeks 12 weeks
SBG 44% 56%
Placebo 17% 31%
SBG® in wound care – clinical data
Biotec Pharmacon ASA 13
Several monts
29 %
Up to one week
8 %Several weeks
26 %
Over 1 year
37 %
• Norwegian survey in 55 patient with mixed wound etiology (most chronic wounds)
• Woulgan used in practical clinical setting in home care and institutions
• 72% of clinicians rated the product good to excellent
How old is the wound?
Diabetic ulcer
18 %
Pressure ulcer
22 %
Leg ulcer
28 %
Post-op. Wound
14 %
Burns
4 %
Lacerations
8 %
Unknown
6 %Poor
10 % Quite good
12 %
Good
25 %Very good
27 %
Excellent
20 %
Don't know
6 %
How would you rate Woulgan’s effect?Wound diagnosis
Agenda
• Company
• Soluble beta-glucan (SBG®) as PAMP
• SBG® as platform for immunotherapeutic applications
• Healing of stalled wounds
• Immunotherapy of cancer
• Summary
Biotec Pharmacon ASA 14
• Enhancing the effector functions of white
blood cells – SBG shown to induce:
• Priming/training of phagocytic white
blood cells to increased cytokine/
chemokine production
• Increased recruitment of phagocytic cells
to site of mAb-labelled cancer cells
• Increased phagocytic and cytotoxic ability
of white blood cells to kill cancer cells
Biotec Pharmacon ASA 15
Biotec SBG® in cancer therapy -mode of action
Macrophages (monocytes) stimulated with beta-glucan or LPS
for 24h and then restimulated 6 days later.
Stimulation with beta-glucan results in macrophages in a
«Trained Immunity» (A) state giving increased cytokine
production (B).
Saeed et al 2014, Science, 345:1578-1589
Biotec SBG® in cancer therapy – animal model
• Biotec’s SBG® has been shown to potentiate
the effect of immuntherapetic cancer regimes:
• Improved anticancer mAb effect
• Improved anticancer vaccine effect
• SBG enhances the immunepresenting capacity
of cells, but more important the effector
functions of white blood cells (tumor killing)
• Biotec’s SBG effective when given orally (p.o.)
Biotec Pharmacon ASA 16
mAB alone
mAB + SBG
Mice inoculated with human neuroblastoma cancer cells,
Treatment with i.v. mAb 3F8 with or without p.o.
administered SBG. Effect measured as tumor size.
(Memorial Sloan Kettering Cancer Center - MSKCC)
SBG® in immunotherapy of cancer
Biotec Pharmacon ASA 17
• Early phase study performed by Memorial Sloan
Kettering Cancer Center in New York
• Increasing doses of p.o administered SBG®
combined with i.v. administered monoclonal mAb
against neuroblastoma in children (45 patients)
• Combination safe and well tolerated
• Positive, but transient treatment effects observed
• Followed up in vaccine trial at MSKCC
Before After
123I-MIBG scan of patient treated with
one cycle of 3F8+SBG (80mg/kg/day)
SBG ® in immunotherapy of cancer
• Investigator driven vaccine trial in children with neuroblastomainitiated by MSKCC using their own developed bi-valent vaccineagainst neuroblastoma antigens (GD2L and GD3L).
• Biotec’s SBG® given p.o. to increase tumor killing activity ofwhite blood cells
• Single arm study
• Phase I part (safety) of studie (15 patients) finalised in 2013
• Combination was safe – and positive responses observed
• Phase II part (efficacy) of study ongoing aiming to recruite 100 patients (115 in total)
Biotec Pharmacon ASA 18
Kushner et al 2014, Clinical Cancer Research 20: 1375-1382
Outlook
Outlook
Biotec Pharmacon ASA 20
• The primary focus of Biotec currently is to secure the full commercial potential of
Woulgan®
• Market penetration in Europe
• Secure the execution of the Post Market Clinical Follow-Up study and local case
study series for KOL support
• Develop follow up products for wound healing based the Woulgan® technology
with SBG®
• The results the ongoing study at Memorial Sloan Kettering Cancer Center will be
important references of SBG® as an adjuvant for cancer theraphies – The Company will
assess follow–up options for developing SBG® within this therapeutic field