Covering a Spectrum of New Product Development Technologies - From Cells to Cell Therapy

Presentation by Stewart McNaull, KBI Biopharma's SVP of Business Development at BIO2017

1. 1
Who we Are
Where we Are
Building on Analytics
Program Experience
Emerging Therapy Platforms
- HIV envelop protein platform
- Bispecific & fusion platforms
KBI Cell Therapy
KBI & Selexis Join Forces

KBI Biopharma
Covering a Spectrum of New Product Development
Technologies - From Cells to Cell Therapy

2. 2
Who We Are
Mission Statement
KBI Biopharma's mission is to accelerate the development of
innovative discoveries into life-changing biological products &
expand global access of medicines to patients in need

3. 3
Durham, NC (2004)
Mammalian

•Cell Line Development
•cGMP Manufacturing & Testing
•Analytical Formulation, Stability
•Mass Spec Core Facility
Boulder, CO (2014)
Microbial

•Strain Development
•Process Development
•cGMP Manufacturing & Testing
•Analytical, Formulation, Stability
•Particle Characterization Core
•Modeling & Simulation
RTP, NC (2013)
Mammalian

•Process & Analytical Development
•Process Characterization
•Small scale Process Validation

The Woodlands, TX (2017)
Cell Therapy

•Process & Analytical Development
•cGMP Manufacturing & Testing
•Cell Based Assays

Where We Are

4. 4
KBI’s Foundation of Analytical Services
Early Discovery Phase 1 Phase 2 Phase 3
Product
Launch
Analytical &
Formulation
Cell Line Development
Upstream
Process Development
Analytical services for >220 molecules:
>100 antibodies products
Enzymes, Cytokines, Growth factors
Highly glycosylated proteins
Protein vaccines, PEGylated proteins
Conjugates, Peptides

Analytical, Development & Manufacturing Services from
early first-in-human (FIH) development & manufacturing
to product launch.

5. 5
KBI’s Foundation of Analytical Services
Early Discovery Phase 1 Phase 2 Phase 3
Product
Launch
Analytical &
Formulation
Cell Line Development
API Manufacturing
Upstream
Process Development
Downstream
Process Development
Analytical services for >220 molecules

Formulation development for >110
distinct molecules:
>60 antibody products
>38 lyophilized products
>30 high concentration products
>10 late stage or commercial products
Multiple dosage forms @ 10-200mg/mL

6. 6
From Analytical Services to Process Development
Early Discovery Phase 1 Phase 2 Phase 3
Product
Launch
Cell Line Development
API Manufacturing
Upstream
Process Development
Downstream
Process Development
Analytical services for >220 molecules

Formulation Dev for >110 molecules

Process & Analytical Development for
>80 molecules:
FIH mAb & non-mAb platforms
High-Throughput PD/AD & PC/PV
50 programs supported in 2015
Upstream
Process Development
Downstream
Process Development
API Manufacturing
Analytical &
Formulation

7. 7
From Analytical Services to Process Development
Early Discovery Phase 1 Phase 2 Phase 3
Product
Launch
Cell Line Development
API Manufacturing
Upstream
Process Development
Downstream
Process Development
Analytical services for >220 molecules

Formulation Dev for >110 molecules

PD & AD >80 molecules

Cell Line Development for >30
molecules:
Antibody & non-antibody products
Client or KBI hosts, vectors, methods


Upstream
Process Development
Downstream
Process Development
Cell Line Development
Analytical &
Formulation

8. 8
From Analytical Services to IND & BLA Enabling API
Early Discovery Phase 1 Phase 2 Phase 3
Product
Launch
Cell Line Development
API Manufacturing
Upstream
Process Development
Downstream
Process Development
Analytical services for >220 molecules

Formulation Dev for >110 molecules

PD & AD >80 molecules

CLD for >30 molecules

cGMP Manufacturing for >24 products
2016: 30 DS batches, 14 IND filings
Successful FDA & EMA Inspections


Upstream
Process Development
Downstream
Process Development
Cell Line Development
API Manufacturing
Analytical &
Formulation

9. 9
Mammalian Process Development: >80 Projects
*
*Includes 5 Biosimilars

10. 10
Development experience:
>50 recombinant clinical targets developed
>10 transferred into GMP
>10 successful client quality audits

Late Stage Experience:
>5 programs into Process Characterization
3 programs into Ph III & PPQ Batches
FDA PAI: 2016 (license pending)
EMA/MHRA: 2017 (pending)
Microbial Development & Manufacturing Experience 14%
11%
11%
8%
9%
9%
9%
6%3%
3%
3%
14%
Molecule Types
immune modulators/cytokines
pegylated proteins
biosimilars
enzymes (therapeutic + critical
reagent)
heme proteins
insulins
growth factors

11. 11
Process Development &
Manufacturing Platforms
for Emerging Therapies
11
Confidential
11

12. 12
Platform approaches have been implemented for monoclonal antibodies and
Fc fusion proteins; however, biochemical differences in non-mAb molecules
of the same class warrant the need for some development efforts (Ɣ).
KBI’s approach for non-mAb emerging therapies is to leverage our
experience to identify and study those parameters that most impact process
robustness and product quality attributes, and to use platform conditions for
the remaining process parameters
Emerging Therapy non-mAb Platforms
(Ɣ) Shukla, A., Hubbard, B., Tressel, T., Guhan, S., Low, D. Downstream processing of monoclonal antibodies
– Application of platform approaches, Journal of Chromatography B, 848, 28-39, 2007.

13. 13
mAb platforms were leveraged to develop bispecific & fusion platforms






5 other bispecific programs are underway

Developing Emerging Therapy Platforms
Project
Type of
Molecule
USPD start
Peak VCD
(10
6
cell/mL)
Titer Range
(g/L)
A mAb Final clone 35 4.5 - 8.5
B Bispecific mAb Final clone 25 3.5 - 4.5
C Fusion protein SCC2 32 - 43 2.2 - 2.8
D Bispecific mAb SCC1 26 - 32 2.6 - 3.0
E Bispecific mAb SCC2 22 - 28 2.1 - 2.7
F Bispecific mAb SCC2 21 - 25 2.0 - 2.4
G Bispecific mAb SCC2 20 - 26 4.2 - 4.8
* 12 Day process vs. standard 14 Days

14. 14
Challenging Emerging Therapies: HIV envelop proteins
A vaccine strategy was devised using gp120
envelop proteins to induce a broadly
Neutralizing antibody CH103 in healthy
individuals

The gp120 envelop proteins are complex
molecules requiring advanced analytics

These molecules are also hard to express & purity


H.X. Liao et al. Nature 496: 469; 2013

15. 15
Parameters shaded in gray are defined across
molecules. Parameters shaded in yellow
require molecule specific optimization
Load & elution conditions for three of the unit
operations require molecule specific definition
given the heterogeneity of this class of
molecules
Env antigens structurally sensitive to
hydrophobic surfaces, hence HIC not
employed

HIV envelop protein DSP Platforms

16. 16
KBI Cell Therapy
The Woodlands, TX

Process/Analytical Development & Manufacturing
for Phase 1 /2 Clinical Cell Therapies

Cell Based Assay Development

Product Fill, Finish, Storage, & Stability

Regulatory Support for IND & CMC Filings

Clinical Specimen Logistics

Therapeutic Monitoring of Patient Response

17. 17
Immunotherapy Products (by Example):

•Chimeric Antigen Receptor (CAR) T-cell
•Chimeric Antigen Receptor (CAR) NK-cell
•Antigen Specific T cells
•Monocyte-derived dendritic cells
•Cellular Vaccines
Regenerative Medicine Products (by Example):

•Enriched tissue-derived stem cell products
•Induced pluripotent stem cell products
•Gene-modified stem cell products

Production Capability for Autologous or Allogeneic Cell Therapy Products

18. 18
KBIs bispecific & fusion platforms utilized Selexis cell lines





KBI Emerging Therapy Platforms
* 12 Day process vs. standard 14 Days
Project
Type of
Molecule
USPD start
Peak VCD
(10
6
cell/mL)
Titer Range
(g/L)
A mAb Final clone 35 4.5 - 8.5
B Bispecific mAb Final clone 25 3.5 - 4.5
C Fusion protein SCC2 32 - 43 2.2 - 2.8
D Bispecific mAb SCC1 26 - 32 2.6 - 3.0
E Bispecific mAb SCC2 22 - 28 2.1 - 2.7
F Bispecific mAb SCC2 21 - 25 2.0 - 2.4
G Bispecific mAb SCC2 20 - 26 4.2 - 4.8

19. © Copyright 2016 Selexis SA. All rights reserved.
Selexis SUREtech™: Rapid Development of Research Cell
Bank
Courtesy of Pierre-Alain Girod, Igor Fisch

20. Selexis Partner’s Success
Selexis • CONFIDENTIAL - NOT FOR DISTRIBUTION
PRECLINICAL IND FILING PHASE III PHASE I PHASE II MARKET
AUTOIMMUNE/INFLAMMATORY
DISEASES
18 1 3 2
BLOOD DISORDERS 1 3 1
CANCER 18 13 8 1 1
METABOLIC/INFLAMMATORY
DISORDERS
2 1 1
DERMATOLOGY/EYE
DISORDERS
1 1
UNDISCLOSED 5
3
MARKETED
PRODUCTS
CLINICAL DRUG
CANDIDATES
1,2 81
More than 95 partners
worldwide
Since 2008
11 R&D licensees

21. 21
Selexis cell lines are used for 3 commercial products & >75 clinical products
including difficult to express proteins
KBI’s mAb, bispecific & fusion platforms have provided titers of 2-10 g/L for 15
Selexis cell lines including GMP Mfg
KBI’s analytical expertise is used to select the best cell lines based on
productivity & product quality


KBI & Selexis Join Forces

22. 22
Leverage KBIs analytical tools to aid
product quality based clone selection,
particularly for new modalities

By combining Selexis CLD & KBI
development platforms we aim to deliver
the most rapid & robust Gene to GMP
platform on the market: DNA to drug
substance in 9 months


Combined KBI-Selexis Platforms

23. Confidential
Acknowledgements

Leslie Wolfe
Niket Bubna
Sigma Mostafa
Brian Ridout
Carnley Norman
Abhinav Shukla
Jimmy Smedley
Wayne Yount
Brandon Vail
Pierre-Alain Girod
Igor Fisch
Tim Kelly
Thank You

24. 24
From Analytical Services to IND & BLA Enabling API
Early Discovery Phase 1 Phase 2 Phase 3
Product
Launch
Cell Line Development
API Manufacturing
Upstream
Process Development
Downstream
Process Development
Analytical services for >220 molecules
Formulation Dev for >110 molecules
PD & AD >80 molecules
CLD for >30 molecules
cGMP Manufacturing for >24 products


Upstream
Process Development
Downstream
Process Development
Cell Line Development
API Manufacturing
Analytical &
Formulation

25. Global Partners Trust Selexis
February 2017 Selexis • CONFIDENTIAL - NOT FOR
DISTRIBUTION
25
THE COMPANY
WE KEEP…

More than 95 global
partners in 23
countries.