1. Clearing the Way for Viral Clearance
Dec. 2018

2. Non-Confidential – Dec 2018
Executive Summary
MockV Solutions is a privately held life science tools company headquartered in Rockville, Md.
We are commercializing a series of research kits that lower the cost and complexities associated with viral clearance during biopharmaceutical process development/characterization
Team of experts from industry, kit commercialization, and business
> $140M market opportunity with no regulatory approvals or clinical trials
MVM-MVP Prototype Kit validated and available for purchase
Beta testing fully commercial version with Industry Partners. Launch expected by mid-2019.
US Patent protected (pending in EU, Japan, others)
Retrovirus Particle Kit development currently funded through FDA grant
Seeking additional ($1.5M) funding
Reduce costs of manufacturing MVM-MVP Kit
Commercialize pipeline products (ex. Retrovirus Particle Kit)
Non-Confidential – Dec 2018

3. Non-Confidential – Dec 2018
Management Team
David Cetlin, MS
10+ years developing biologic drug manufacturing processes
Albine Martin, PhD
20 + years of operating and product commercialization experience
Dale Dembrow
30+ years of Assay Development, Kit Production and manufacturing
20+ years of industry and academic vaccine research
Arun Dhar, PhD
Non-Confidential – Dec 2018

4. Biopharmaceutical Process Development
Developing a manufacturing process to produce a purified biopharmaceutical is:
Complex – numerous interdependent steps
Time-consuming –activities estimated >6 years1
Expensive –activities estimated $50-100M1 2 4
Non-Confidential – Dec 2018
Building a Business Case for Biopharmaceutical QbD Implementation. Beth Novker, BioPharm International 25(8) 2012
Sommerfeld, S.; Strube, J. Challenges in biotechnology production—Generic processes and process optimization for monoclonal antibodies. Chem. Eng. Process. 2005, 44, 1123–1137.

5. No kit for measuring virus
Reliance on Kits
HCP
DNA
Protein A
Endotoxin
Virus ?
No kit for measuring virus
Non-Confidential – Dec 2018

6. Viral Clearance - Problem
Regulatory Agencies requires proof of “viral clearance” before clinical or commercial approval
The only way is to conduct a live-virus study is in a specialized facility. 2 F = =
This is what triggered me to start MockV Solutions.
Increased
Risk of Failure
Expensive
In the Dark 6
Non-Confidential – Dec 2018
Building a Business Case for Biopharmaceutical QbD Implementation. Beth Novker, BioPharm International 25(8) 2012

7. The Solution
Research kits that provide cost-effective viral clearance data on the benchtop
Replaces Live Virus with Non-infectious Mock Virus Particles (MVP)
Kit includes all components necessary to perform 10 viral clearance tests
Different kits that model different viruses
Mock Virus
Quantify mock virus
1. Spike sample with MVP
2. Run sample through purification process step
3. Quantify remaining MVP
Non-Confidential – Dec 2018

8. Value Proposition – Biopharmaceutical Companies
Customers would benefit from using MVP Kits throughout process development and beyond
Test new products
Predict potential failures prior to REQUIRED viral clearance validation (ex. IND filing)
Generate Viral Clearance data during process development
Generate Viral Clearance data during process characterization (ex. DOE studies)
Predict potential failures prior to REQUIRED viral clearance validation (ex. BLA filing)
Deviation support, 2nd gen development.
Non-Confidential – Dec 2018

9. Value Proposition – Biopharmaceutical Companies
MVP Kits are the most accurate, economic and convenient method to generate predictive viral clearance data
Method
Prediction Accuracy
Cost/experiment
BSL-I Compatible
Analysis Duration
Commercial Availability VF
Chrom.
Standard Regulatory Validation Method
Viral Clearance studies
N/A
> $3,000 No
> 4 weeks
Yes
Current Predictive Methods
Bacteriophage
No Data
No1
1-3 Days
MVP Method
MVP Kits
$350
1 Day
Pending
(1) Certain strains of bacteriophage are BSL-1 compatible; however, many labs choose not to risk introduction of them into their facilities. Other strains are BSL-2.
Non-Confidential – Dec 2018

10. Comparable Research Kits
Low Adoption Risk
Downstream process development relies on commercial kits
MVP Kits fit into existing paradigm
Comparable Research Kits
MVP Kits
HCP Protein
DNA
Protein A
Endotoxin
Virus ?
Non-Confidential – Dec 2018

11. Primary end User and Customer Segment
Customer Segments
Biopharmaceutical
Companies
Primary end User and Customer Segment
Assay value realized at multiple points along drug development pathway.
Low adoption Risk - assay fits into existing paradigm
Accurate, economic and convenient method to generate predictive viral clearance data
Industry Vendors
Viral Clearance CRO’s
Internal use
Enable cost-effective viral clearance testing during new products and technology R&D:
Virus Filtration
Chromatography
External
Offer viral clearance kits to accompany small-scale purification products
Link customers to company at an early stage and throughout process development and characterization
External (as supplier of service)
Expand viral clearance services to include a low cost predictive viral clearance service marketed throughout process development, characterization, etc.
Links customers to company at an early stage and throughout process development /characterization leading to regulatory viral clearance study.
Non-Confidential – Dec 2018

12. Lead Product: MVM-MVP Kit
MVM-MVP Spike stock and quantification reagents for ~ 10 small scale experiments
Product Guide detailing use
Component
Stock Concentration
Quantity/Volume
MVP Antibody Coated Microplates NA 3
MVP Spiking Stock Solution
1E12 MVP/mL
1.5 mL
MVP Standard
25 uL
Biotinylated anti-MVP Antibody
20X
2 mL
NeutrAvidin
Biotin-Target DNA.
Forward Primer. 1X
300 uL
Reverse Primer.
Probe
200 uL
Blocking Buffer 3X
20 mL
Assay Diluent
50 mL
Wash Buffer
150 mL
Recovery Buffer
18 mL
Master Mix 2X
4 mL
Nuclease Free water
Plate Sealers 12
Non-Confidential – Dec 2018

13. “Mock Virus Particles (MVP)”
Minute Virus of Mice (MVM) selected as first MVP candidate
MVM is a small, non-enveloped parvovirus commonly used as a model virus during viral clearance validation studies
Purified MVP was examined by Transmission Electron Microscopy (TEM) after negative staining
270,000x
95-98% of MVP’s were intact. 
Little to no cellular or proteinaceous debris
MVP concentration of ~1012 particles/ml 13
Non-Confidential – Dec 2018

14. Physicochemical Characterization and Comparison to Live MVM
Collaboration with FDA
Published in Applied Biochemistry and Biotechnology. Johnson, S., Brorson, K.A., Frey, D.D. et al. Appl Biochem Biotechnol (2017) 183: 318.
Analyzed MVM-MVP, live MVM, and bacteriophage for:
Size (SEC-MALS, TEM)
Surface Charge (Chromatofocusing)
Hydrophobicity (HIC-HPLC Assay) 14
Non-Confidential – Dec 2018

15. Non-Confidential – Dec 2018
Physicochemical Characterization
and Comparison
TEM images of viral particles at 110,000x magnification after negative staining.
Left: infectious MVM Right: MVM-MVP.
Particles of each species were found to be overall intact and evenly distributed. The darker area within some MVM and MVM-MVP particles is thought to be caused by dye penetrating into the structure.
Transmission Electron Microscopy
Live MVM (Texcell)
MVM-MVP 15
Non-Confidential – Dec 2018

16. Physicochemical Characterization and Comparison
Analysis
Live MVM
MVM-MVP
PP7 Bacteriophage
Hydrodynamic Radii (MALS)
18.4 ± 0.2 nm
17.2 ± 0.1 nm
16.9 ± 0.4 nm
Diameter (TEM)
24.6 ± 3.6 nm
25.6 ± 3.0 nm
31.6 ± 1.6* nm
Surface Charge (pI)
5.99
5.81
4.74
Hydrophobicity**
0.28
0.35
0.61
* Reference value from Lute et. al. PDA J Pharm Sci Technol (2008)
** Relative hydrophobic affinity to Phenyl (1.0 = insulin)
MVM-MVP’s mimic the physicochemical characteristics of live MVM
Indicates utility in predicting physicochemical-based removal of live MVM 16
Non-Confidential – Dec 2018

17. MVP Quantification Assay
Current (pAb based) Immuno-qPCR Assay
Current assay yields ~3 log dynamic range
High background due to Immuno assay component (controls not shown)
Potential to reduce background, increase dynamic range to > 4 logs, improve sensitivity. 17
Non-Confidential – Dec 2018

18. Non-Confidential – Dec 2018
Assay Improvement
Prototype
Commercial-pending
~ 8 hours to perform
Dynamic range ~ 3.0 log10
LOQ of ~ 1.0 x 106 particles/mL
Requires heat-block step
pAb based
~ 4 hours to perform
Dynamic range ≥ 4.0 log10
LOQ of ≤ 5.0 x 105 particles/mL
No heat-block step
mAb based 18
Non-Confidential – Dec 2018

19. Non-Confidential – Dec 2018
Assay Improvement 19
Non-Confidential – Dec 2018

20. (0 MVP/mL asymptote – trendline value) Non-Confidential – Dec 2018
Assay Improvement
Δ Ct
(0 MVP/mL asymptote – trendline value)
Test
1E6 MVP/mL
5E5 MVP/mL
1E5 MVP/mL
Comm. Assay
3.1
2.4
0.9
Comm Assay
3.0
2.3
0.8
Prototype Assay
1.2
0.3
-1.8
1.0E+05
1.0E+06
0 MVP/mL asymptotes
1.0 log10 improvement on “high end”
~ log10 improvement on “low end
Comm Assay 1
Comm Assay 2
Prototype Assay 20
Non-Confidential – Dec 2018

21. Collaborations
Proof of Concept collaborations with industry partners and government agencies
Collaborator
Kit Version
Brief Description
Status
Notes
Asahi Kasei
MVM-MVP Prototype
Compare MVM clearance and flux decay for Planova and BioEX
Completed (Published in Biotechnology Progress)
Voted best presentation at Planova User Conference 2018 (S.F.)
MedImmune
Compare MVM clearance for virus filtration and AEX
Completed (pending publication)
Voted best poster at 2018 Recovery Conference (Ashville, N.C.)
NIH (Vaccine Research Center)
Screen resins for MVM clearance in High Throughput Screening format (Tecan).
Biotech Co. #1
Commercial Pending Kit
Compare MVM clearance for AEX (DOE)
Funded through NIH grant
Biotech Co. #2
Compare MVM clearance for mixed mode chromatography DOE
Anticipated completion in Q1 2019
Industry Vendor
Screen HIC resins for MVM Clearance
Biotech Co. #3
Commercial MVM-MVP Kit
Compare MVM clearance for gene therapy process
Pending Phase II Grant Funding
Biotech Co. #4
Compare MVM clearance for continuous processing
Biotech Co. #5
RVLP Kit Prototype
Compare XMulV clearance
Anticipated completion by mid 2019
Funded through FDA grant
Non-Confidential – Dec 2018

22. Non-Confidential – Dec 2018
Asahi/Texcell Study
Purpose of Study was to:
Establish pAb assay at Texcell and replicate standard curve
Conduct preliminary studies on Planova/BioEX filters to determine maximum MVM-MVP spike
Conduct MVM vs. MVM-MVP “spiking studies” and analyze/compare clearance data
Publicize
Non-Confidential – Dec 2018

23. Proof of Concept Results
Phase I- Assay Transfer
Lower Quantification Limit (QL) calculated to be 4.1 x 105 MVM-MVP’s/mL
Dynamic range of ~ 3.5 log10 particles
Non-Confidential – Dec 2018

24. Proof of Concept Results
Phase II- Preliminary Studies
Spiked “representative” material (containing 0.1 g/L h-IgG) with various amounts of MVP
Processed ~150 mL through PlanovaTM 20N “P20”.
Collected Load and Pool samples and ran on Immuno-qPCR
Low Spike
8.0 log10 Particle Challenge
(6.7x 105 MVM-MVP/mL)
Medium Spike
9.7 log10 Particle Challenge
(3.3x 107 MVM-MVP/mL)
High Spike
11.0 log10 Particle Challenge
(6.7x 108 MVM-MVP/ml)
P20
P20
P20
Non-Confidential – Dec 2018

25. Proof of Concept Results
Phase II - Filter Performance Results
Flux decay data demonstrates consistency among range of MVP spikes
11.0 log10 particle challenge selected for further study
Non-Confidential – Dec 2018

26. Proof of Concept Design
Phase III – MVM vs. MVM-MVP spiking studies
Series of experiments utilizing:
PlanovaTM BioEX, PlanovaTM 35N or PlanovaTM 20N
Buffer or IgG matrix (150 mL’s per experiment)
MVM or MVP spike
Particle
Total Particle Challenge
System
P20 Experiments
BioEX Experiments
P35 Experiments
None NA
IgG 1
MVM
~8.5 log10 TCID50
Buffer 2
MVP
11.0 logs10 particles
Non-Confidential – Dec 2018

27. Non-Confidential – Dec 2018
Filtration Results
Comparable filter performance among MVM, MVM-MVP or no spike runs
Non-Confidential – Dec 2018

28. Non-Confidential – Dec 2018
P20 IgG LRV Results
MVM
(Target: 8.5 log10 TCID50)
MVM-MVP
(Target: 11.0 log10 Particles)
IgG Matrix only
Exp.1
Exp. 2
Exp. 1
Load
Pool
TCID50 Results (TCID50/mL)
9.8 x 105
≤1.4 x 101
[LOQ] NA
I-qPCR Results (I-qPCR Particles/mL)
6.8 x 108
≤ 4.1 x 105
[QL]
2.5 x 108
≤ 4.1 x 105 [QL]
Volume (mL)
154
164
162
151
153
150
158
Total TCID50 or I-qPCR Particles
1.5 x 108
≤ 2.3 x 103
≤ 2.2 x 103
1.0 x 1011
≤ 6.3 x 107
3.7 x 1010
≤ 6.5 x 107
Log10 (Total TCID50 or I-qPCR Particles)
8.2
≤ 3.4
11.0
≤ 7.8
10.6
LRV
≥ 4.8
≥ 3.2
≥ 2.8
Non-Confidential – Dec 2018

29. Non-Confidential – Dec 2018
BioEX IgG LRV Results
MVM
(Target: 8.5 log10 TCID50)
MVM-MVP
(Target: 11.0 log10 Particles)
IgG Matrix only
Exp. 1
Exp. 2
Load
Pool
TCID50 Results (TCID50/mL)
6.8 x 105
≤ 1.4 x 101
[LOQ]
9.8 x 105 NA
I-qPCR Results (I-qPCR Particles/mL)
1.4 x 109
≤ 4.1 x 105
[QL]
1.8 x 109
Volume (mL)
144
150
157
148
162
159
Total TCID50 or I-qPCR Particles
9.8 x 107
≤ 2.1 x 103
1.4 x 108
≤ 2.2 x 103
2.1 x 1011
≤ 6.6 x 107
2.7 x 1011
≤ 6.5 x 107
Log10 (Total TCID50 or
I-qPCR Particles)
7.99
≤ 3.31
8.15
≤ 3.33
11.3
≤ 7.8
11.4
LRV
≥ 4.7
≥ 4.8
≥ 3.5
≥ 3.6
Non-Confidential – Dec 2018

30. P35 (Control) LRV Results Non-Confidential – Dec 2018
IgG Matrix only
MVM
Target 8.5 log10 TCID50
MVM-MVP
Target 11.0 log10 particles
Load
Pool
TCID50 Results (TCID50/mL)
1.2 x 106
9.8 x 105 NA
I-qPCR Results (particles/mL)
3.5 x 109
1.4 x 109
Volume (mL)
157
158
150
TCID50 or particles
1.9 x 108
1.6 x 108
5.2 x 1011
2.1 x 1011
log10 (TCID50 or particles)
8.3
8.2
11.7
11.3
LRV
0.1
0.4 30
Non-Confidential – Dec 2018

31. Asahi/Texcell Conclusions
Comparable filtration of MVM and MVM-MVP spiked loads
MVM and MVM-MVP completely removed by P20 and BioEX (below assay limits)
Complete passage of MVM-MVP through P35, as expected
≥ 3 logs of MVM-MVP removal calculated through current I-qPCR assay
MVM-MVP particles non-infective via TCID50 (data not shown)
MVM particles quantifiable via I-qPCR (data not shown)
Manuscript published in Biotechnology Progress
Non-Confidential – Dec 2018

32. MedImmune/Texcell Collaboration
Purpose of Study was to:
Demonstrate MVM vs. MVM-MVP clearance comparability via Virus Filtration and Chromatography
Demonstrate acceptable Spike/Recovery in representative matrix
Demonstrate acceptable Hold Time for samples containing MVM-MVP
Test Texcell Service Model (in parallel to in-house analysis)
Publicize 32
Non-Confidential – Dec 2018

33. Spike/Recovery with Representative Material
Spiked representative matrices (and PBS control) to 1 x 107 MVM-MVP’s/mL
Analyzed via Immuno-qPCR (with un-spiked matrices as control)
mAb
Salt
Matrix Ref. #
Representative of.. -
Low 1
High (400mM) 2
AEX strip samples + 3
AEX Load and Pool
High(400mM) 4 5
VF Load, Pool, Chase
100%
84.5%
89.7%
71.6%
122.3%
110.6% 33
Non-Confidential – Dec 2018

34. Non-Confidential – Dec 2018
Sample Hold Study
Spiked MVM-MVP into each matrix at 1.0 x 109 MVM-MVP/mL
Stored at either 4°C or -80°C
Analyze via Immuno-qPCR fresh (Day 0) and after 4, 7, 14 and 21 days
MVM-MVP sample is stable for up to 21 days at 4°C or -80°C with presence of protein
MVM-MVP sample is stable for up to 21 days at -80°C in absence of protein 34
Non-Confidential – Dec 2018

35. Proof of Concept: Chromatography
Spiked MVM-MVP into AEX load: target starting concentration of 1.0 x 109 particles/mL
Processed through AEX column (1 x 20 cm) and collected flow through pool
Initiated a salt gradient ( mM, 10 CV’s) followed by a 1M Strip and took fractions
Analyzed all samples via Immuno-qPCR
Calculated MVP/mL
Reported MVP/mL
Volume
Total MVP
Log10 Total MVP
LRV1
Load
7.75E+08
236.38
1.83E+11
11.26
≥ 3.30
Product
2.28E+05
≤ 3.28E+05
279.03
≤ 9.16E+07
≤ 7.96
1. LOQ limiting 35
Non-Confidential – Dec 2018

36. Non-Confidential – Dec 2018
AEX: MVM vs. MVM-MVP
Based on previous study, 4 salt concentrations were selected for testing
9.0, 20.0, 23.0 and 41.0 mS/cm
Spiked MVM-MVP to target 1.0 x 109 particles/mL
Spiked MVM to target > 8.0 log10 TCID50/mL
Processed and Analyzed via I-qPCR (MVM-MVP) and TCID50/mL (MVM)
Spike
Condition (mS/cm)
Log10 total Load
Log10 total Product
Log10 Reduction value
MVM-MVP 9
11.31
≤8.26
≥3.06 20
11.25
≤8.27
≥2.99 23
11.33
8.95
2.38 41
11.22
11.3
MVM
8.19
≤3.52
≥4.67
8.58
5.19
3.39
8.50
6.76
1.74 
8.02
8.42 36
Non-Confidential – Dec 2018

37. MedImmune/Texcell Conclusions
Comparable nanofiltration (flux and LRV results) for MVM vs MVM-MVP (data not shown)
Acceptable spike/recovery and hold time in representative matrices
MVM-MVP predictive of MVM for AEX in 3/4 conditions tested (LOQ limiting)
Manuscript published submitted for publication
Non-Confidential – Dec 2018

38. Non-Confidential – Dec 2018
Next Steps
Complete beta testing of fully commercial MVM-MVP Kit (Q1 2019)
Improved dynamic range of quantification assay
Decreased assay time
Performing beta testing proof of concept studies with industry collaborators
Manufacture and launch commercial MVM-MVP Kit (Mid-2019)
Prototype available now
Reduce COG’s related to MVM-MVP Kit manufacturing (YE resource dependent)
- Internalize MVM-MVP production (began Q3 2018)
Develop and commercialize Retrovirus-Like Particle Kit (YE resource dependent)
- Obtained $150k Phase 1 grant from FDA to begin development 38
Non-Confidential – Dec 2018

39. David Cetlin, Founder and CEO
(301)
Dec 2018