A presentation about our collaborative research projects at Complex Biotech Discovery Ventures.

1. Collaborative Research for
Fundamental Insight into
Cannabis Production
Dr. Markus Roggen

2. Fundamental Collaboration
• Fundamental Questions
• Collaboration, Current
• Fundamental Research
• Collaboration, Future

3. Fundamental Questions
• What to produce?
• Which cannabis cultivar is the right one?
• How to grow cannabis?
• How to process cannabis?
• How to extract cannabis?
• How to formulate cannabis extracts?
• How to treat patients with cannabis products?

4. A Mature Market Demands Cannabis Extracts
Concentrates may surpass flower as the #1 product in the US.
2017 2022
Flower
Concentrates
Edibles
Other
Source: Arcview & BDSAnalytics Cannabis Intelligence Briefing

5. A Mature Market Demands Cannabis Extracts
NorthAmerica’s expansion (2015: $5bn to 2018: $11bn) reduces cannabis price

6. Type of Cannabis Extracts
There is a dizzying array of products available and various extraction methods.
• Hash, Rosin
• Shatter, wax
• Distillate, Isolate
• Crude, HTFSE, …

7. Complex Biotech Discovery Ventures
CBDV is a young research venture that seeks to add fundamental scientific
insight to the field of cannabis production.
We seek to support the cannabis industry by establishing a centralized
hub in Vancouver, BC for collaborative research focused on:
• Process Design
• Process Optimization
• Process Analytics
• Formulation Research

8. CBDV’s Collaborative Research
CBDV collaborates with academic, industry and private groups around the
globe. Some highlights of those collaborations are:
• University of British Columbia, Vancouver
• Loyalist College, Belleville
• Vialpando, LLC by Dr. Monica Vialpando
• Veridient Science by Dr. Linda Klumpers
• Fritsch Milling
• PerkinElmer

9. Fundamental Questions
• What to produce?
• Which cannabis cultivar is the right one?
• How to grow cannabis?
• How to process cannabis?
• How to extract cannabis?
• How to formulate cannabis extracts?
• How to treat patients with cannabis products?

10. Fundamental Questions
• What to produce?
• Which cannabis cultivar is the right one?
• How to grow cannabis?
• How to process cannabis?
• How to extract cannabis?
• How to formulate cannabis extracts?
• How to treat patients with cannabis products?

11. Processing Extracts
Decarboxylation is one of the most critical processing steps.

12. How do You Decarboxylate?
There is a lack of universal agreement regarding reaction conditions.
• Oven heating
• Hot plate
• Microwave
• Oil bath
• Other?

13. Don’t Decarboxylate to Long
Problems of excess heating:
• Availability of instruments
• Higher costs of production
• Side reaction and degradation
• Lower yields
0
10
20
30
40
50
60
70
80
0
0.5
1
1.5
2
2.5
3
3.5
0 1000 2000 3000 4000 5000 6000
THC
THC(%)
CBN&d8-THC(%)
d8-THC
CBN
Elapsed Time (Minutes)

14. Reaction Monitoring of Decarboxylation
Current
• Subjective determination of reaction completeness
• Reactionary approach
• Inconsistent batches
• Lack of quality & process control
vs. Optimal
• Rapid
• Simple
• Accurate
• Small sample volume

15. In-Process Analytics
Infrared spectroscopy is a useful tool for reaction monitoring.
BG62-64 T0
Name
Sample 023 By Administrator Date Thursday, July 12 2018
Description
1750 8001600 1400 1200 1000
0.23
-0.01
-0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
0.16
0.18
0.20
0.22
cm-1
A
_ Start THCA
20.87 %
End THCA
1.56 %

16. Monitoring THCA In-Process
0
5
10
15
20
25
30
35
0 10 20 30 40 50 60 70 80
THCA(%)
Elapsed Time (Minutes)

17. Monitoring THCA In-Process
16
26
36
46
56
66
76
16 26 36 46 56 66 76
Predicted%THC
Reference % THC

18. Monitoring THCA In-Process
0
5
10
15
20
25
30
35
0 10 20 30 40 50 60 70 80
THCA(%)
Elapsed Time (Minutes)

19. Monitoring THCA In-Process
Why bother?
Optimization Precision Decarboxylation

20. Decarboxylation Observation
Not all Decarboxylations are equal

21. Collaboration: Computational Studies
Steric vs. Electronic: Exploring the Rate Difference in THCA and CBDA
Decarboxylation
1T-S1 1C-S1
Bot View
THCA CDBA
Top View

22. Collaboration: Computational Studies
kJ/mol
0
50
100
150
200
0 1 2 3 4 5 61T 1C
1C-S1(MeOH) 1C-S3(MeOH)
1C-TS2(MeOH)
1T-TS2(MeOH)

23. Collaboration: Computational Studies
Key Findings:
• Rate determining step is the intermolecular protonation
• Rate difference is due to steric rather than electronic effects
1C-TS2(MeOH)

24. Fundamental Questions
• What to produce?
• Which cannabis cultivar is the right one?
• How to grow cannabis?
• How to process cannabis?
• How to extract cannabis?
• How to formulate cannabis extracts?
• How to treat patients with cannabis products?

25. What is Cannabis?
• Indica vs. Sativa
Phylos Bioscience

26. What is Cannabis?
• Indica vs. Sativa
• Strain names

27. What is Cannabis?
• Indica vs. Sativa
• Strain names
• High THC vs. high CBD
John S. Abrams, PhD; The
CESC

28. Chemovars
• Indica vs. Sativa
• Strain names
• High THC vs. high CBD
• Chemovars

29. Chemovars
Hazekamp, et al.; Cannabis and Cannabinoid Research 2016, 1.1
• Indica vs. Sativa
• Strain names
• HighTHC vs. high CBD
• Chemovars

30. Chemovars
Orser C, Johnson S, Speck M, HilyardA,Afia I (2018)TerpenoidChemoprofiles Distinguish Drug-type
Cannabis sativa L. Cultivars in Nevada. Nat ProdChem Res 6: 304.
• Indica vs. Sativa
• Strain names
• HighTHC vs. high CBD
• Chemovars

31. Chemovars
• Indica vs. Sativa
• Strain names
• High THC vs. high CBD
• Chemovars
DiscOmic by Digamma Consulting

32. Unknown unknowns
CBDV’s Metabolite Database

33. Unknown unknowns
CBDV’s Metabolite Database
• 24 compound categories
• 762 compounds

34. Unknown unknowns
CBDV’s Metabolite Database
• 24 compound categories
• 762 compounds
• 75 cannabinoids
• 416 terpenes

35. Known unknowns
Solubility data from literature & in-house data
Solubility of cannabinoids in supercritical CO2 at 326K
K.H. Perrotin-Brunel et al. / J. of Supercritical Fluids 55 (2010) 603–608

36. Known unknowns
Solubility data from literature & in-house data
% Decarb
THC/THCA
S.M. 7h 22h
SuperCrit 8.0% 25% 10%
SubCrit 14% 25% 14%
CBG/total
Canna.
S.M. 7h 22h
SuperCrit 2.9% 6.% 2.9%
SubCrit 3.0% 13% 4.9%

37. Unknown knowns
DoE surfaces of solubility

38. Fundamental Questions
• What to produce?
• Which cannabis cultivar is the right one?
• How to grow cannabis?
• How to process cannabis?
• How to extract cannabis?
• How to formulate cannabis extracts?
• How to treat patients with cannabis products?

39. Collaboration: Extraction Optimization
For what:
• Yield per Run YpR
• Yield per Week YpW
• Cannabinoid Conc. CC
• Terpene Content TC
• Recovery Rec
• …
With what:
• Temperature T
• Pressure P
• Time t
• Flow Rate FR
• Particle Size PS
• …

40. Size does Matter
Small and even particle size enables:
• Higher packing density
• Improved extraction efficiency
20
22
24
26
28
30
32
34
Non-Ground Food
Blender
2 mm 6 mm 10 mm
%Recovery
Cannabinoid Recovery by Size
75
80
85
90
95
Non-Ground Food
Blender
2 mm 6 mm 10 mm
%Recovery
Terpene Recovery by Size

41. Collaboration: Extraction Optimization
Temperature (˚C)
Pressure (psi)
Yield THC (g)
34
60 1100
1900
47
1500
0

42. Collaboration: Extraction Optimization
Temperature (˚C)
Pressure (psi)
Yield THC (g)
34
60 1100
1900
47
1500
0

43. Collaboration: Extraction Optimization
Temperature (˚C)
Pressure (psi)
Yield THC (g)
34
60 1100
1900
47
1500
0

44. Collaboration: SFE Database

45. Collaboration: SFE Database

46. Collaboration: SFE Database

47. Collaboration: SFE DoE
SFE optimized for single separator
Cannabinoid Concentration

48. Collaboration: SFE DoE
SFE optimized for single separator
Cannabinoid Yield

49. Fundamental Collaboration
• Fundamental Questions
• Collaboration, Current
• Fundamental Research
• Collaboration, Future

50. Collaborative Data Analysis
cbdvl.com/freedata
• Free extraction data analysis file
• Basic analysis tools
• Send back for in-depth analysis (info@cbdvl.com)

51. Collaborative Data Analysis
cbdvl.com/freedata
• Free extraction data analysis file
• Basic analysis tools
• Send back for in-depth analysis (info@cbdvl.com)

52. Thank You
Thanks go to our collaborators:
• Blake Grauerholz, OutCo
• Taylor Trah, OutCo
• Dr. Allison Justice, Hemp Mine
• Ariel Bohman, PerkinElmer
• Dr. Toby Astill, PerkinElmer
• Barry Schubmehl, Fritsch Milling
• Antonio Marelli, Imperial College
• Weiying He, UBC

53. CBDV Team
Luiz Geraldo – VP Finance
Currently pursuing his MBA, Luiz is an Industrial
Engineer and has 5 years of experience in strategy
and operations consulting and strategic planning.
Gursaanj Singh Bajaj – Data Science Associate
Gursaanj is an Astrophysics major in the
department of Physics and Astronomy at UBC, with
a background in data analysis. He will be going into
his 4th year of his undergraduate degree.
Kendra Payne – VP Business Operations
Experienced Program Manager/Coordinator and
Senior Administrator with a demonstrated history of
working in the education management and
biotechnology industries. Skilled in Biotechnology,
Project Coordination and Life Sciences.
Callum MacPhee – Business Associate
Callum is a going into his fourth year at the
University of British Columbia and is pursuing
a Bachelor of Commerce.
Sajni Shah – Research Associate
Currently studying Chemical Biology in the
Department of Chemistry at UBC. She is
going into her final year of her undergraduate
studies.
Klara Wyse – Marketing Associate
Klara is a Media Studies and Urban Studies
student at UBC, going into their fourth year.

54. Dr. Markus Roggen markus@cbdvl.com