Chimerix : Corporate Presentation

Chimerix

Corporate

Presentation

May 1, 2024

Forward-Looking Statements

This presentation contains 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. Forward-looking statements include those relating to, among other things, the enrollment and timing of data for the Phase 3 ACTION study, the expected results of Phase 3 ACTION study of ONC201 and dose escalation trials of ONC206, our ability to successfully commercialize our current and future product candidates, the potential for royalty and milestone revenue from strategic collaborations, and projections regarding the potential market opportunity, funding and timing of future data readouts for our products. Among the factors and risks that could cause actual results to differ materially from those indicated in the forward-looking statements are risks related to the timing, completion and outcome of the Phase 3 ACTION study of ONC201; risks associated with repeating positive results obtained in prior preclinical or clinical studies in future studies; risks related to the clinical development of ONC206; 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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Investment highlights and key catalysts

Ph 3 ACTION study	Significant	Corporate capability
actively enrolling	commercial potential	and financial flexibility

ONC201 Ph 3 trial enrolling - interim OS data expected in 2025, final OS expected in 2026

First-Line H3 K27M-mutant diffuse glioma - The ACTION Study

• No approved therapies targeting H3 K27M diffuse glioma, an area of high unmet medical need
• First in class mechanism of action with clinical validation
• Patent protection thru 2037 (potential additional US patent term extension)

ONC206 in dose escalation

• Investigator reported response in non-H3 K27M mutated recurrent glioblastoma patient
• Dose escalation on track for completion beginning in mid 2024

Early-stage pipeline leverages external capital

• Pre-clinicalprograms potential to advance to clinic or partner (ONC212, CMX521)
• Robust business development search and evaluation process

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$188 million in capital to fund operations as of March 31, 2024, no debt

Deep pipeline across all development stages

	Program	Preclinical	Phase 1	Phase 2	Registrational	Regulatory
	Approval
	ONC201 (dordaviprone)
	H3 K27M-mutant glioma (orphan drug,1 fast track2 and rare pediatric disease designations3)
	IITs- signal finding, multiple oncology indications/combinations
	ONC206
	CNS4 tumors
	Non-CNS4 tumors
	ONC212
	IND-enabling studies
	CMX521
	SARS-CoV-2

TEMBEXA® transacted with Emergent BioSolutions

Smallpox (orphan drug designation)

	1	Malignant glioma
4	2	Adult recurrent H3 K27M-mutanthigh-grade glioma
3	H3 K27M-mutant glioma
	4.	Central Nervous System

ONC201 (dordaviprone) Phase 2 Data Analysis

ONC201 data suggests potential to address high unmet need

• H3 K27M mutation is predominantly found among diffuse midline gliomas (DMGs) in young adults and children
• Frontline radiotherapy remains standard of care with transient benefit; resection often not feasible

Frontline H3 K27M DMG2	Histone H3 Mutations
	in CNS Tumors1

• DMGs harboring the H3 K27M mutation are

WHO Grade IV; historically invariably lethal
• Consistently longer OS of ONC201-treated		Recurrent H3 K27M DMG3
H3 K27M DMG patients across:
- Diverse external controls (historical, trials)		Natural Disease History4	ONC201 Phase 2
	(n=43)	(n=50)
- Sensitivity analysis (early event censoring)
Median OS, mo (95% CI)	5.1	13.7
- Isolated tumor locations (thalamus, brainstem)		(3.9-7.7)	(8-20.3)
OS @ 12mo (95% CI)	23.6%	57%
		(11.7-37.9)	(41-70)
	OS @ 24mo (95% CI)	11.1%	35%
		(3.3-24.2)	(21-49)

1. Lulla RR et al. Sci Adv. 2016;2(3):e1501354
2. Koschmann, Carl et al, "Clinical efficacy of ONC201 in H3 K27M-mutant diffuse midline glioma is driven by disruption of integrated metabolic and epigenetic pathways", Cancer Discovery, Aug 16, 2023

6 3 In company sponsored studies

4 The median OS was 5.1 months for the subset of patients with H3 K27M-mutant diffuse glioma excluding DIPG, CSF dissemination, spinal or leptomeningeal disease (N=12), OS at 12 mos was 25.0%, OS at 24 mos was 16.7%

Phase 2 efficacy for ONC201 in recurrent H3 K27M DMG

• ONC201 monotherapy exhibited durable, clinically meaningful efficacy in recurrent H3 K27M-mutant DMG

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Overall Response Rate (ORR) of 30% (95% CI: 18 - 45%) by RANO HGG and/or LGG dual reader BICR RANO-HGG criteria assessed by dual reader BICR

• ORR 20% (95% CI: 10 - 34%)
• Median Duration of Response (DOR) 11.2 months (95% CI: 3.8 - not reached)
• Median time to response 8.3 months (range 1.9 - 15.9)
• Disease control rate 40% (95% CI: 26 - 55%)
• PFS at 6 months 35% (95% CI: 21 - 49%); PFS at 12 months 30% (95% CI: 17 - 44%)

• • RANO-LGGcriteria assessed by dual reader BICR
  • • ORR 26% (95% CI: 15 - 40%)
  • Overall survival
  • • 12 months: 57% (95% CI:41 - 70%)
    • 24 months: 35% (95% CI: 21 - 49%)
• Improvements observed in performance status and reduction in corticosteroid use
• All Serious Adverse Events considered not related to ONC201 by sponsor

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ONC201 waterfall plot - 30% RANO HGG / LGG response

ONC201 Ph 2 Efficacy Analysis by BICR in Recurrent H3

K27M-mutant Diffuse Midline Glioma

RANO HGG (enhancing)

• 20% response
• 40% disease control

• Strict selection criteria to ensure responses attributable to single agent treatment
• Responses require both imaging and clinical criteria
• Dual reader blinded independent central review (BICR)

RANO LGG (non-enhancing)

• 26% response
• 42% disease control

• Growing consensus that assessment of enhancing and non-enhancing disease (RANO- HGG and RANO-LGG criteria) is needed for diffuse midline glioma

Change > 100%, PR=partial response, MR=minor response, SD=stable disease, NE=not evaluable, PD=progressive disease

8 Arrillaga-Romany, et al, Journal of Clinical Oncology, Feb 2024

Clinically meaningful and durable RANO-HGG responses

ONC201 Phase 2 Efficacy Analysis by BICR in Recurrent H3 K27M-mutant Diffuse Midline Glioma

Duration of response,	11.2 months
median (95% CI)	(3.8 - not reached)
Time to response,	8.3 months
median (range)	(1.9 - 15.9)

SPD=sum of products of perpendicular diameters (target enhancing lesions per BICR)

Only patients with measurable target enhancing lesions by BICR at baseline and with post-baseline evaluations are included.

9	Three patients did not have on-treatment monotherapy MRIs available for BICR; one patient censored prior to first on-treatment MRI ; one patient did not have measurable target lesion.

ONC201 Safety

Clinical Pharmacology Studies n=235

• ONC201 was well tolerated at various dose levels (125 mg to 750 mg).
• The majority of treatment-related adverse events across the clinical pharmacology studies were Grade 1 (mild) and transient.
• Most common treatment-related AEs were grade 1 nausea and dizziness.
• ONC201 in the clinical pharmacology program, which included:
• • Dose-escalation,food-effect, & formulation evaluation
  • Thorough QT Study
  • Drug-druginteraction (DDI) studies: Strong CYP3A4 inhibitor and Proton-pump inhibitor studies
  • Renal impairment study
  • Hepatic impairment study
  • Mass balance study
  • Formulation Bioequivalence studies

Glioma Patient Studies

Treatment-related Adverse Events in >5%

Treatment-related Adverse Events,	Related TEAEs
Integrated Safety Data Set,
All grades	Grade > 3
(N=422 glioma patients) 1
Any Treatment-related AE	56.2%	11.6%
Fatigue	20.1%	2.1%
Nausea	15.4%	0
Vomiting	11.1%	0.9%
Lymphocyte count decreased	9.2%	1.9%
ALT increased	8.5%	1.4%
Headache	7.3%	0
White blood cell count decreased	7.1%	0.2%
Decreased appetite	5.7%	0
Hypophosphataemia	5.2%	0

Only 3% patients experienced a treatment-related AE that

led to study drug modification or discontinuation.

10	1.	Based on available data from October 2023 Investigator brochure