HUMAN ANTIBODY DISCOVERY BASED ON RENMAB/RENLITE/RENNANOTM MICE AND PIPELINE ASSETS OF 1000+ TARGETS - @LSX FEB. 2021 - SWAPCARD
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Human Antibody Discovery Based on
RenMab/RenLite/RenNanoTM Mice and
Pipeline Assets of 1000+ Targets
@LSX Feb. 2021
The New Antibody Drug Source Beijing ·Haimen ·Boston ·Shanghai
Biocytogen Corporate Overview
- Innovation Driven Biotech based on Proprietary Ab Discovery Technology, 1000+ Target Abs in Pipeline
• Global biotech founded in 2008, Series D+ funding of $142M in 2020, Boston/Beijing/Shanghai/Haimen
Company
• Founded by renowned immunologist, and experienced pharma industry leaders.
Overview • Total employees 1000+ as of Nov. 2020
• Eucure (Beijing) Biopharma Co., Ltd is a wholly owned daughter company, highly experienced global
clinical and regulatory team.
Platform RenMabTM / RenLiteTM /RenNanoTM Platform tech allows fully integrated/streamlined derisked fully
human antibody discovery & development in various formats: Abs, BsAbs, NanoBodies,
Technology • Fully human antibody: RenMab MouseTM, for the generation of fully human antibodies
• Knocking-out target genes on RenMab, followed by human antigen immunization: to identify
antibodies cross-reacting to the orthologs of human and other species such as monkeys, mice, and
dogs
• Antibodies for FIC/BIC/challenging targets (such as GPCR): via RenMab and target-KO platform
• Beacon system: to obtain antibody sequences in days
• Rapidly obtain candidates: expedited in vivo efficacy and safety screening
• Project Integrum: 1000+ Targets of Abs
Pipeline • Evergreen pipeline with strategic focus: auto-immune, immuno-oncology, anti-inflammatory
diseases: CVD/CKD/Nash, anti-infection etc.
• Internal and Collaboration Pipline Assets: Ab/BsAb/ADC/Cell Therapy/Oncolytic Virus/etc
LSX World Congress 2021
Integrated Antibody Discovery at Biocytogen
-from Gene Targeting to Clinical Trial
Mouse Rat
Genome
Editing
Clinical Three antibody drugs in Phase I
Human ES, iPS Other Strong clinical research team
Other cell lines animals
Trial
Three core techniques (ES, EGE
(CRISPR/CAS9), Chromosome Gene
Engineering)
Developing about 1,500 novel gene- Targeting Pharmacology
targeted animal models yearly
Study
In vitro and Ex vivo tests
In vivo efficacy test using CDX, PDX,
Animal or humanized mice models
Manufac- Antibody
Research Discovery
turing
Campus I Haimen, Campus I I Haimen,
15,000 Square Meters 110,000 Square Meters
Large scale B-NDG® mice and
humanized mice production. Effective lead-discovery strategy (Hybridoma,
Phage display, Single B cell(Beacon))
LSX World Congress 2021
Biocytogen Proprietary Technology Platforms
-Fully Human Antibody Mice Based for mAb/BsAb/NanoBody Generation
• RenMab-based platform: Fully human de-risked therapeutic drug
Common Light ChainHeavy Chain Only
discovery (diversity, differentiation, REAL humanness, quality,
accelerated timeline etc.)
• RenMab-based KO together with Beacon functional screening and
in vivo efficacy validation make it possible to grab high hanging
fruits that are traditionally difficult to reach
• Beyond RenMab: common light chain mouse (RenLite) and VH only
mouse (RenNano) etc. expand Biocytogen’s capabilities from RenMab RenLite RenNano
antibody discovery to biologics discovery
LSX World Congress 2021
Summary of Humanized Antibody Mouse Models in the Field
-RenMab has more human-like repertoire, robust immune responses, high clinical success
LSX World Congress 2021
RenLite: Common Light Chain Mouse for Bispecific Antibody Development
-Address the VH/VL Mispairing Issue
RenLite™ Mice from RenMabTM
7 LSX World Congress 2021
Summary of Common Light Chain Antibody Mice in the Field
-RenLite: allows heavy chain diversity; more human-like repertoire/VDJ recombination;
Mouse Models Company Species Light Chain Light Chain Location
Huamn IGKV3-15-JK1 by BAC homologous
OmniFlic Ligand Rat Insertion site unknown
recombination
Human IGKV1-39-IGKJ1or IGLV2-14 by BAC
MeMo Merus Mouse Insertion into the Rosa site
homologous recombination into ROSA site
Common light chain Human IGKV1-39-JK5 or IGKV3-20-JK1 by BAC
Regeneron Mouse In situ replacement
mouse homologous recombination
Human IGKV3-11-JK1 (and others in the
RenLite Biocytogen Mouse In situ replacement
development) by chromosome engineering
8 LSX World Congress 2021
Pilot Discovery with RenLite for BsAb with a Membrane Protein
-RenLite is Very Productive
Clone Name ka (1/Ms) kd (1/s) KD (M)
O40-BC-1B1-IgG1 1.90E+05 1.42E-04 7.47E-10
O40-BC-1B4-IgG1
O40-BC-1B8-IgG1 1.58E+05 3.35E-04 2.12E-09
O40-BC-1E12-IgG1 6.78E+04 1.42E-03 2.09E-08
O40-BC-1A7-IgG1 2.66E+04 6.34E-04 2.38E-08
O40-BC-1F9-IgG1 1.19E+05 5.95E-03 5.01E-08
O40-BC-1E7-IgG1 3.13E+04 1.96E-03 6.26E-08
O40-BC-1E1-IgG1 1.79E+03 3.82E-04 2.14E-07
O40-BC-1D10-IgG1 1.81E+02 5.65E-04 3.13E-06
O40-BC-1C5-IgG1 2.17E+02 7.57E-04 3.49E-06
O40-38-1D12-1A1-IgG1 6.59E+04 1.62E-04 2.46E-09
O40-B-H8L8 2.46E+05 3.66E-03 1.49E-08
O40-B-H7L7 2.33E+05 4.83E-03 2.07E-08
O40-B-H10L10 1.40E+05 3.91E-03 2.79E-08
O40-B-H3L3 4.96E+04 2.44E-03 4.93E-08
O40-B-H6L6 6.95E+04 5.57E-03 8.03E-08
9 LSX World Congress 2021
Biocytogen Integrated Antibody Drug Development Process
- In Mice Screening as Initial Instead of In Vitro
Target Antibody In vivo In vitro Antibody PK/PD/ Clinical
identification development efficacy tests Production and CMC Tox trial
Antibodies cross- In vivo Efficacy
react with human, PK/PD
mouse and dog TOX/MTD
targets Pet drug development
Pet Hospital
KO target on
RenMab mice
Mouse clinical Pet clinical Human Clinical
LSX World Congress 2021
Project Integrum (RenMabTM+KO)
-https://renmab.com, 1000+ Targets of Abs/BsAbs to Build Internal Pipeline and External Collaboration
• A Project to challenge difficult
targets using RenMab +
Knockout
• For targets with high homology,
generate more antibodies with
different epitopes
• Obtain multi-species (human,
mouse, dog, monkey) cross-
reacting antibodies, which is
conducive to later in vivo drug
efficacy and safety evaluation
• Improve the chance to obtain
antibodies to difficult targets
such as GPCRs
• To further verify the target
through the KO model
LSX World Congress 2021Progess of Biocytogen Early Pipeline Assets
finsished In vivo efficacy
No. of Pipeline Assets
screening
2020Q2 2020Q4 2021Jan 2021Mar 2021May 2021Jul 2021Sept 2021Nov 2022Jan 2022Mar 2022May 2022Jul 2022Sept
LSX World Congress 2021Early Discovery Pipeline
-Leading assets including BsAbs to post data at AACR 2021
Therapeutic Area
Anti-Infection
Auto-immune
Endocrine/metabolism
Nervous/Mental
Oncology
Tetanus Neutralizing Ab
PDL1xCytokine
PD-1
dog CTLA-4
Leads
13 LSX World Congress 2021GPCR Initiatives
-An Important Category of Biocytogen's Pipeline
1. RenMabTM+KO with beacon: allows a large number of antibody sequences Target RenMab KO
GPRC5D Initiated
for high throughput screening.
ADIPOR1
2. Obtained antibodies likely: cross-recognized by multiple species, C5AR1 Initiated
convenient for downstream screening/Safety assessment. GLP1R
GCGR F0 to F1 breeding is ongoing
3. Multiple immunization methods including DNA immunization: increase Ednra
the diversity of antibodies produced. CNR1
CRTH2 Initiated
CXCR5 Initiated
• Largest membrane protein
CXCR3 Initiated
family, ca.825 GPCR ， 370 CXCR2 Initiated
druggable targets CCR9
CCR6
• Two appproved antibody drug CCR2 F0 to F1 breeding is ongoing
targets:CCR4， CGRPR CCR4 Initiated
CXCR4 Initiated
CCR8
CCR7
CX3CR1
CCR5 Initiated
Hutchings 2020
LSX World Congress 2021Proprietary Clinical and Pre-clinical Pipeline
- Open for global partnership, Many others coming soon
LSX World Congress 2021YH001 (anti-CTLA-4 mAb) 2nd Generation with Improved Efficacy
-Good Safety and Efficacy Signal in the Ongoing Phase 1, for Phase 2 NSCLC/HCC Planned
Part 2 Expansion Cohorts/Phase II
Part 1 Dose Escalation (3+3)
Indication:
Key Inclusion criteria: • advanced Non-Small Cell Lung Cancer (NSCLC)
• Advanced solid tumor progressed on after 6 mg/kg N=3-6
• advanced Hepatocecullar Carcinoma (HCC)
treatment with standard therapies or
intolerant of standard care.
• Measurable disease; ECOG performance 4 mg/kg N=3-6 Cohort 1
status score 0 or 1 • Advanced NSCLC, untreated
Key Exclusion criteria: • YH001+Toripalimab
2 mg/kg N=3-6
• History of ≥ Grade 3 immune-related AE or • N=20
any AE leading discontinuation from
RP2D
previous immunotherapy Cohort 2
1 mg/kg
• Prior CTLA-4 therapy or intolerable to • Advanced HCC progressed on or after 1L
N= 3-6
prior PD-1/L1 treatment (sorafenib / Lenvatinib) or intolerant of
Note: Each dose cohort will include
Dosing regimen: 0.3 mg/kg run-in phase (YH001 monotherapy) standard care.
• YH001: 0.05-6 mg/kg N= 3-6 and combination phase (YH001 • YH003+Toripalimab
• Toripalimab: 240 mg combined with Toripalimab). • N=20
• iv Q3W 0.1 mg/kg
N= 3-6 Dose regimen:
For both Cohort 1 and Cohort 2
• Toripalimab (240mg fixed) + YH001 RP2D
0.05 mg/kg
• iv Q3W.
N= 1
Primary endpoint: ORR
Primary endpoint: safety/tolerability and MTD/RP2D of combination treatment Secondary endpoint: Safety; PFS, DCR, etc.
Secondary endpoint: PK and preliminary anti-tumor activities (ORR, DCR etc.)
LSX World Congress 2021YH002 (anti-OX40 mAb) Boost Efficacy with IO and Good Safety
-Good Safey in Ongoing Phase 1, Orphan Indication+SCLC for Phase 2 Planned
LSX World Congress 2021YH003 (anti-CD40 Agonist mAb) with Improved Liver Safety
-Good Clinical Safety in Ongoing Phase 1+ 1 PR at 0.1mg/kg already
Part 1 Dose Escalation (3+3) Part 2 Expansion Cohorts/Phase II
Key Inclusion criteria: Indication: advanced Melanoma and advanced
• Patients with advanced solid tumor progressed on after treatment with standard therapies or Pancreatic ductal adenocarcinoma (PDAC)
intolerant of standard care.
• Serum creatinine 50 ml/min Cohort 2A
Key Exclusion criteria: • Advanced melanoma progressed after
• Grade ≥3 irAEs or irAEs that lead to discontinuation of prior immunotherapy PD1/L1 therapy
Dosing regimen: • YH003+Toripalimab
• YH003: 0.03-3 mg/kg • N=20
• Toripalimab: 240 mg/kg (fixed) 3 mg/kg N=3- Cohort 2B
• iv Q3W 6 • PDAC Progressed on or after 1L chemo
FOLFIRINOX or nab-paclitaxel/GEM
RP2D
1 mg/kg • YH003+Toripalimab
N= 3-6 • N=20
Note: Each dose cohort will Cohort 2C
0.3 mg/kg • Untreated PDAC
include
N= 3-6 • YH003+Toripalimab+Nab-PTX+Gem
run-in phase (YH003
monotherapy) and • N=20
0.1 mg/kg
combination phase (YH003
N= 3-6
combined with Toripalimab). Dose regimen:
• 2A and 2B: Toripalimab (240mg iv q3w, fixed) + YH003 RP2D iv Q3W.
0.03mg/kg • 2C: Toripalimab (240mg iv q3w, fixed) + YH003 RP2D or lower iv Q3W
N= 3-6 plus Nab-paclitaxel+Gemcitabine (standard dose).
Primary endpoint: ORR
Primary endpoint: safety/tolerability and MTD/RP2D of combination treatment
Secondary endpoint: Safety; PFS, DCR, etc.
Secondary endpoint: PK and preliminary anti-tumor activities (ORR, DCR etc.)
LSX World Congress 2021Business Collaboration
- Leverage Strengths, Provide Flexibilities, Pursue Win-Win,
Biocytogen's technology and evergreen pipeline are open for Disclosed Partners (selected):
• License Deal
I
• Co-development
II
• Technology Platform Licensing
III
Existing Internal and Collaboration Pipelines Include Various Formats of Modalities:
mAbs/BsAbs/Cell Therapy/ADC/Oncolytic Virus/etc.
LSX World Congress 2021Thank you for your attention Contact: Vivian Tian, PhD, MBA Email: vivian.tian@bbctg.com.cn Web: https://biocytogen.com
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