Healthspan analysis is a huge part of longevity study, which is heavily looked at by many aging labs in recent years. The older we grow, our health will be affected accordingly, and this influence what type of compound we use. To better picture what effects compounds brings to us and to extend lifespan as a goal. A three stage compound assessment is developed by IVB to solve this question.
2. Longevity and Health Effect
Healthspan analysis is a huge part of
longevity study, which is heavily
looked at by many aging labs in recent
years. The older we grow, our health
will be affected accordingly, and this
influence what type of compound we
use. To better picture what effects
compounds brings to us and to extend
lifespan as a goal. A three stage
compound assessment is developed
by IVB to solve this question.
4. InVivo Biosystems
4
InVivo Biosystems
is the market leader for early in-vivo testing using small animal models
to gain a better understanding of
the efficacy, mode of action, toxicity and potential targets of novel compounds.
Right Model. Right Test. Right Insights.
5. In-Vivo Testing: Obtain the Data You Need
5
The Nematode Caenorhabditis elegans The Zebrafish Danio rerio
COMPOUND TESTING TOXICITY ANALYSIS LIFESPAN HEALTHSPAN AGING STUDIES
Research Idea
Experimental Hypothesis
Project / Pipeline Goal
YOUR:
Complete Data Package
Fully Analyzed Results
Data-Backed Conclusions
YOUR:
InVivo Biosystems:
IN-VIVO
WHOLE-ORGANISM TESTING
6. InVivo Biosystems: Your On-Call Lab
6
Nutraceutical
Biopharma
Biotech
Pharmaceutical
COMPANY NEED
PROJECT SCOPE
TACTICAL
Select Experiments
or Models
STRATEGIC
Early-Mid
Project Phases
MAXIMAL
Full Project
Completion
7. Nutraceuticals + Healthy Aging
7
Nutraceutical
Biopharma
Biotech
Pharmaceutical
COMPANY NEED
PROJECT SCOPE
TACTICAL
Select Experiments
or Models
STRATEGIC
Early-Mid
Project Phases
MAXIMAL
Full Project
Completion
“Nutraceuticals may be used to
improve health, delay the aging process, prevent chronic
diseases, increase life expectancy, or support the
structure
or function of the body.”2
US nutraceutical market expected to reach
> $138 billion USD by 2027.3
Global nutraceutical market expected to
reach > $302 billion USD by 2022.4
Nutraceutical
8. Nutraceutical Market Drivers and Pain Points
CHALLENGES
DRIVERS RESTRAINTS
Strong Consumer Interest:
- anti-aging, general
- longevity and health
- skin care
- heart disease
- aging-related disease
Resources and Time Cost:
- high cost of raw material production
- limited supply of quality manufacturing materials
- long development pipeline increases production cost
- lengthy lab-to-market timeline if animal testing involved
Increasing Competition and Awareness:
- growing competition as new players continuously enter market
- increasing awareness among consumer base demands validation of claims
- results must be backed by scientific evidence of efficacy AND safety
8
10. Common Model Systems, Known Pitfalls
HTS of 1000’s of compounds
Fast data turnaround
X No organ-system
complexity
X No whole-organism effects
No HT possibilities X
Long timelines X
Full organ system complexity
Human-relevant dosages
Regulation
Resources / Cost
Experimental Timeline
Model Complexity
Cell Culture Mice
Relevance to Human
10
11. The InVivo Biosystems Approach
HIGH QUALITY DATA – FAST TURNAROUND – LOW COST
MEDIUM THROUGHPUT – LOW REGULATION
model systems capable of providing the detailed answers necessary to pursue your research aims
Regulation
Resources / Cost
Experimental Timeline
Model Complexity
Cell Culture MiceFishWorms
Relevance to Human
11
12. EARLY
go/no-go decision making
FAST
experiment turn-around
ECONOMICAL
pipeline
Nutraceutical Market Need: IVB Delivers
12
We focus on
proof-of-principle experiments
that provide the preliminary data necessary to quickly and confidently
make go/no-go decisions
during early-stage investigations.
13. The IVB Process: Simple. Effective. Fast.
13
INTRODUCTION
Understand
Your Goal
DESIGN
Create A
Personalized Catalog
LOGISTICS
Finalize Your Project
Design
REPORT OUT
Maintain Clarity and
Transparency
[ 3 MONTHS ]
14. INTRODUCTION
Understand
Your Goal
DESIGN
Create A
Personalized Catalog
LOGISTICS
Finalize Your Project
Design
REPORT OUT
Maintain Clarity and
Transparency
[ 3 MONTHS ]
Your Data Package, Your Next Move
14
MARKETING MATERIALS
PRESS RELEASE
INVESTOR MEETINGS
FUNDING ROUNDS
GRANT PROPOSALS
PATENT
APPLICATIONS
DEVELOPMENT
PIPELINE
WHITE PAPERS
SCIENTIFIC
PUBLICATIONS
15. InVivo Biosystems Platform Solutions
15
The Nematode Caenorhabditis elegans
LIFESPAN +
HEALTHSPAN
The Zebrafish Danio rerio
In Vivo TOXICITY
TESTING
CUSTOM DESIGN
SOLUTIONS
16. The Longevity Platform – 3 Stages
16
LIFESPAN +
HEALTHSPAN
QUESTION
What are the effects of a compound on
lifespan, healthspan, and transcriptional
changes related to aging?
What is the mechanism of action?
STAGE I
Dosage
Optimization
STAGE II
Data
Collection
STAGE III
Molecular
Analysis
17. IVB Longevity Compound Assessment: Stage I
17
Stage I: DOSAGE OPTIMIZATION
- Rule out possible toxicity.
- Test for most suitable downstream dosage.
- Determine… a) whether full longevity experiment suitable;
b) if so, at what compound dosage/under what conditions.
[Drug]
GFP
constitutive
RFP
induced
EC50
18. IVB Longevity Compound Assessment: Stage I
18
Fig. 1.1:
EC50 determined for
compound Lu0128.
Fig. 1.2:
Viability, growth, and
development toxicity
analysis for compound
Lu0128.
Xenobiotic Stress Oxidative Stress
C. elegans Length C. elegans Development
19. 19
IVB Longevity Compound Assessment: Stage II
Stage II: DATA COLLECTION
- Specific metrics as pertinent to experiment.
- Monitor animals for survival, morphology, specific movement patterns, etc.
- Generate a full, high-resolution and multi-dimensional data set.
20. 20
IVB Longevity Compound Assessment: Stage II
Stage II: DATA COLLECTION
- Specific metrics as pertinent to experiment.
- Monitor animals for survival, morphology, specific movement patterns, etc.
- Generate a full, high-resolution and multi-dimensional data set.
21. 21
IVB Longevity Compound Assessment: Stage II
Stage II: DATA COLLECTION
- Specific metrics as pertinent to experiment.
- Monitor animals for survival, morphology, specific movement patterns, etc.
- Generate a full, high-resolution and multi-dimensional data set.
N = 75
ΔT = 3
days
P = 0.15
N = 150
ΔT = 1
day
P =
0.014 N = 300
ΔT = 1
hour
P =
0.0000054
High Resolution Analysis
22. IVB Longevity Compound Assessment: Stage II
22
Fig. 2.1:
Survival and hazard
rate curves from
lifespan assay.
Survival Rate Hazard Rate
Fig. 2.2:
(L) Morphological
features analyzed, and
(R) Principal
Component Analysis
(PCA) of multi-
dimensional data set.
Principal Component
Analysis
23. 23
IVB Longevity Compound Assessment: Stage III
Stage III: MOLECULAR ANALYSIS
- Perform whole transcriptome analysis (WTA).
- Delve into mechanism of action.
- Identify pathways and players responsible for observed effects.
Fig. 3.1:
Volcano plot depicting
gene expression
change in compound-
treated v. untreated Day
10 adult worms.
C.e. Day 10 Adults
24. 24
IVB Longevity Compound Assessment: Stage III
Longevity Pathway Analysis
Fig. 3.2:
Gene expression
analysis comparing
compound-treated v.
untreated Day 10 adult
worms, grouped by
pathway.
26. Case Use: Compound Analysis for ENCo*
26
*Company name and other identifiers have been altered to maintain confidentiality.
Company: European Nutraceutical Company (ENCo)
A small European-based nutraceutical company focused on developing…
- natural extracts and compounds that have the ability to promote healthy aging;
- food supplement formulations for the improvement of human vitality and longevity.
Company’s Need:Move very RAPIDLY from HYPOTHESIS to early PROOF-OF-CONCEPT
27. Case Use: Compound Analysis for ENCo*
27
ENCo:
“While mammalian models are currently the gold standard for drug
development,
the enforced 3Rs and animal welfare guidelines have required us to re-evaluate our
development pipeline to include early stage in-vivo hypothesis testing.
Understanding the biology of our compounds necessitates the use of an
alternative model prior to going to more regulated, more resource and time-intensive
models.”
3Rs of Animal Use in Research
REPLACE REDUCE REFINE
28. Case Use: Compound Analysis for ENCo*
28
ENCo’s Hypothesis / Question:
A. Do ENCo’s selected compounds (Compound A and Compound B) have any whole-organism effect on animal
longevity?
B. If so, what is the mechanism driving Compound A and Compound B efficacy?
C. How does ENCo characterize Compound A and Compound B to advance progress towards clinical applications?
29. Case Use: Compound Analysis for ENCo*
29
ENCo’s Goal:
Identify a single compound or synergistic compound mixture with the most positive and reproducible effect on
longevity.
ENCO’s Framework:
- Data that is directly relevant to human health and the whole-body system.
- Short 6-month timeline to encompass experimental design, preparation, execution and analysis of results.
- Data to be formatted and available for use in patent application(s).
ENCO’s Requirements:
- Seeking whole-organism, in-vivo data
rather in-vitro experiments.
- Seeking fast, reliable and biologically
relevant data in a whole-animal model.
- Avoiding associated cost, timeline and
regulatory paperwork of rodent models.
30. Case Use: Compound Analysis for ENCo*
30
ENCo’s Challenges:
- In-vitro data alone not suitable or sufficient for downstream patent application needs.
- Rodent models are gold standard for in-vivo work, but too time consuming and too costly at this stage.
The In-Vivo Biosystems Solution
Using the small animal model C. elegans,
we proposed and executed a specific set of experiments designed by our expert team to address ENCo’s specific
research goals, and to provide rapid and reliable data based upon the company’s short-term priorities and long-term
aims.
Population
Locomotion
Individual
Locomotion
Molecular
Phenotyping
Lifespan
Assessment
Healthspan
Assessment
31. Case Use: Compound Analysis for ENCo*
31
Kaplan-Meier survival curve depicting results of compound impact on C. elegans lifespan.
ENCo – Sample Data Acquired:
Lifespan
Assessment
Lifespan assay tracking individual worm lifespan within a population;
percent of worm population surviving (y-axis) versus time in days (x-axis).
32. Case Use: Compound Analysis for ENCo*
32
Electropharyngeogram (EPG) results depicting contraction of the pharyngeal muscle in C. elegans adult worms.
ENCo – Sample Data Acquired:
Individual
Locomotion
Frequency of contraction of the pharyngeal muscle (left) and
amplitude of contraction of the pharyngeal muscle (proxy for
strength of muscle contraction, right).
33. Case Use: Compound Analysis for ENCo*
33
Achieved Outcome:
Using the data that we generated, ENCo was able to…
- obtain conclusive and reproducible data within their allotted timeframe;
- apply for multiple patents in a timely manner;
- ultimately moved forward with further development of lead compounds revealed during the project.
Animal
Model
Conditions
Tested
Assays
Utilized
Figures/Table
s
Generated
Project
Time
Project
Cost
Patent
Applications
1 15 $45,500 12 4 13 1 +
ENCo ANALYSIS: BY THE NUMBERS
C.
elegans
weeks USD
34. INTRODUCTION
Understand
Your Goal
DESIGN
Create A
Personalized Catalog
LOGISTICS
Finalize Your Project
Design
REPORT OUT
Maintain Clarity and
Transparency
Case Use: Compound Analysis for ENCo*
34
MARKETING MATERIALS
PRESS RELEASE
INVESTOR MEETINGS
FUNDING ROUNDS
GRANT PROPOSALS
PATENT
APPLICATIONS
DEVELOPMENT
PIPELINE
WHITE PAPERS
SCIENTIFIC
PUBLICATIONS
35. InVivo Biosystems
35
In-Vivo Biosystems
is the market leader for early in-vivo testing using small animal models
to gain a better understanding of
the efficacy, mode of action, toxicity and potential targets of novel compounds.
Right Model. Right Test. Right Insights.