Chimerix : International Conference on Antiviral Research 2022 Presentation

The nucleoside analog antiviral CMX521 inhibits SARS-CoV-2 in human airway epithelial cell cultures and exhibits prophylactic and therapeutic efficacy against respiratory disease in a mouse model of SARS-CoV-2 infection

ICAR March 23, 2022

Randall Lanier

Forward-Looking Statements

These slides contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Among the factors and risks that could cause actual results to differ materially from those indicated in the forward-looking statements are risks that the current pre-clinical or clinical study data for CMX521 will not support accelerated, or any, regulatory approval; risks that ongoing or future studies/trials may not be successful or replicate previous trial results, or may not be predictive of real-world results or of results in subsequent trials; risks and uncertainties relating to competitive products and technological changes that may limit demand for our drugs; risks that our drugs may be precluded from commercialization by the proprietary rights of third parties; and additional risks set forth in the Company's filings with the Securities and Exchange Commission. These forward-looking statements represent the Company's judgment as of the date of this release. The Company disclaims, however, any intent or obligation to update these forward-looking statements.

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Novel coronavirus outbreaks occurring every 6-8 years

8,000			>450mm
	2,500
SARS-CoV Outbreak (2002 - 2004)	MERS-CoV (2012 - 2021+)	SARS-CoV-2 (2019 - 2022+)
• 9.6% case fatality rate (CFR)	•	35% CFR	• Highly infectious with a 1-2% CFR
• 774 fatalities attributed	•	889 fatalities attributed	• >6 million fatalities attributed

What's Next ?

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CMX521: Direct-acting antiviral delivered to key site of viral

replication to enhance efficacy and safety

CMX521…

• Ribonucleoside triphosphate inhibits norovirusRdRp*
• Oral formulation developed through Phase I
• Excellent safety profile in GLP tox studies
• No significant inhibition of human DNA polymerase α, β, or γ, RNA polymerase Type II or mitochondrial RNA polymerase at ≤ 200 µM CMX521-TP
• Well-toleratedin healthy volunteer Phase I study up to highest dose tested (2400 mg)

*Confirmation in SARS-CoV-2 RdRp ongoing

…for SARS-CoV-2

• Low µM in vitro activity across diverse coronaviruses
• In vivo efficacy in SARS-CoV-2-MA10mouse-model
• Inhalation administration maximizes respiratory exposure while minimizing systemic exposure
• Primed for rapid development to clinical POC due to prior development through Phase I

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Oral CMX521 formulation developed through Phase 1 study

Favorable safety profile in nonclinical species and humans with well-characterized nonclinical ADME profile

• CMX521 not mutagenic, clastogenic, cytotoxic or mitotoxic and demonstrated no significant off-target pharmacology
• Oral formulation developed for norovirus disease
• 7-dayrepeat dose LOAEL plasma exposures in dog > 10x human plasma exposure with 2.4 g oral dose
• • No adverse toxicity identified in rat with 14-days repeat dosing ≤ 2000 mg/kg/day
  • Mouse PK study exhibited low plasma exposure with inhaled administration of efficacious doses
• Phase 1 single ascending dose study in healthy volunteers (≤ 2400 mg; n = 38 subjects)
• • No SAE's, AE-related withdrawals, clinically significant changes in vital signs, ECGs or clinical laboratory parameters and no dose or exposure relationship to TEAEs

• Well-characterized metabolic and transporter interaction profile	H2N	O	NH2
-	Minimal DDI potential
	- Elimination primarily via urine and bile as parent			N
	- Characterization of nucleoside and efflux transporters complete	O	N	N
• Drug substance process robust and scalable to large kg scale batches
HO
	- Manufactured 20 kg GMP clinical batch; stability > 36 months	HO	OH
-	Polymorph study completed enabling post-POC formulation optimization
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