Simulations Plus : Lunch & Learn – SOT 63rd Annual Meeting and ToxExpo

What's New at Simulations Plus,

Your Partner in Winning, for

Exposure and Safety Assessment!

SOT Lunch

and LearnFun!

March 11, 2024

1	NASDAQ: SLP | CONFIDENTIAL

Session Topics

• Simulations Plus Overview and News
• Machine Learning / AI + PBPK + QST: What's the Fuss?
• Exposure and Property Prediction Updates
• Bridging Exposure to Safety Outcomes for Therapeutic Development
• Questions Please!

2	NASDAQ: SLP | CONFIDENTIAL

Who We Are

NASDAQ: SLP

200+

Employees

Worldwide

>280 Pharmaceutical, biotechnology, chemicals, cosmetics, and consumer goods companies in the U.S., Europe, Asia, and South America

3	NASDAQ: SLP | CONFIDENTIAL

Regulatory Agencies

Using our Technology

>25 yrs.

Established

In 1996

Confidence Level on Clinical Performance

Complementary Solutions

Clinical Pharmacology & Pharmacometrics

Decrease development uncertainty, cost, time, and failure rates.

Exposure

Dose

Regulatory/

NCA

Post

Response

Optimization

PBPK / PBBM

Market

QSP: Inflammatory,

Approval

Immune-Oncology, &

DDIs

Population

PopPK

PK/PD

Autoimmune Diseases

Predictions

QST: Safety

Food

Produc

Safety

Pediatric

t

Prediction

Effects

Design

s

PhysChem

Local &

IVIVC &

Efficacy

Systemic

Virtual

Exposure

BE

Model Integrated Data

ADME

Toxicity

First-In-

Empirical Data

Human

AI / ML Cheminformatics

"…combining models and data results in higher confidence in clinical performance at an earlier time in development."

U.S. Food & Drug Administration

4	NASDAQ: SLPTime| CONFIDENTIAL

What's it Like to Work with Us?

We believe the relationships we build with our clients are critical for mutual success

A highly interactive collaboration not only allows us to deliver results as quickly as possible, but also ensures a higher quality deliverable

• Regular interactions ensure the relevancy of results as the knowledge-base continues to evolve
• Transparency provided by progress updates eliminates surprises
• Synergies come from a shared knowledge-base of expertise and experience
• Involvement, participation, and input from stakeholders outside of M&S is welcome

THALES

5	NASDAQ: SLP | CONFIDENTIAL

Hot Off the Presses…..

6

How to Engage with SLP, Here and Elsewhere?

[e-mail] - Director, Business Development

• • Simulations Plus Website:https://www.simulations-plus.com/
• Resource Center (publications, webinars, posters, etc…)https://www.simulations-plus.com/resource-center/
• Events! (workshops, webinars, conferences, training, etc…)https://www.simulations-plus.com/events/

7	NASDAQ: SLP | CONFIDENTIAL

The Machine Learning / PBPK / QSP(T) Marriage… A Winning Combination!

Permeability,	Local & systemic
solubility vs. pH,	exposure, drug
pKa(s),	distribution,
logD vs. pH,	parent and
Fup,	metabolite
blood:plasma	levels,
ratio, tissue Kps,	patient
CLint, CLfilt	variability

8	NASDAQ: SLP | CONFIDENTIAL

Mechanistic Modeling to Support Regulatory Interaction: The Push!

FDA Guidance Document

2018

PMDA Guidance Document

EMA Guidance Document

2018

2020

OECD Guidance Document

2021

9	NASDAQ: SLP | CONFIDENTIAL

What Else Is Driving Increased Adoption of M&S?

Experimental and Study Costs!

Prompts written into ChatGPT 4: 02Mar2024

	Basic Toxicity Tests		More Complex Toxicity Tests
	•Acute	Toxicity Studies: Costs can range from		•Subchronic (90-day) Toxicity Studies:		These
	$5,000	Costs continue to		rise at high rates.			300,000,
	route				includes
	the
	•Skin						Studies:
	tests can Stop thinking of M&S as an expense…	million.
	Reproductive
	•	start thinking of it	as an investment!	tests can
	from $
	•Reproductive Toxicity Studies: These studies can		•Endocrine Disruptor Screening: These tests can
	cost between $300,000and $1 million, depending		vary widely in cost, from $20,000for simple
	on the complexity and species used.		assays to over $1 millionfor a full set of studies.
10		NASDAQ: SLP | CONFIDENTIAL