Chimerix

Corporate

Presentation

November 2, 2023

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 probability of success of the Phase 3 ACTION study, the potential filing and approval of an NDA for ONC201 and subsequent commercial opportunity, the implications of the monotherapy radiographic partial response observed during ONC206 dose escalation; the ability to reproduce clinical and pre-clinical findings, and projections regarding funding and timing of future data readouts. 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.

2

Investment highlights

High probability of success

Low barriers to

Corporate capability

for Phase 3 ACTION study

commercial potential

and financial flexibility

of ONC201

for ONC201

  • Phase 2 study designed to isolate single agent activity in difficult treatment setting
  • Durable responses associated with OS and other forms of clinical benefit
  • Numerous independent and natural disease history studies support potential survival advantage
  • Genetically selected patient population limits patient heterogeneity

3

  • Terminal disease with no effective therapeutic options
  • High awareness for program within neuro-oncology community
  • U.S. patent exclusivity through at least 2037
  • Global revenue potential of ~$750m in first indication alone
  • Leadership team successfully executed large scale studies and regulatory approvals
  • Strong balance sheet fully funds ACTION study and potential ONC206 catalysts
  • Opportunity for continued non- dilutive TEMBEXA milestones and royalties adds flexibility
  • Track record of objectivity in creating paths to capture value

Deep pipeline across all development stages

Program

Preclinical

Phase 1

Phase 2

Registrational

FDA review

Collaborators

ONC201 (dordaviprone)

H3 K27M-mutant glioma (orphan drug,1 fast track2

and rare pediatric disease designations3)

IITs- signal finding, multiple oncology indications/combinations

ONC206

National Institutes

of Health

CNS4 tumors

ONC212

IND-enabling studies

CMX521

5

SARS-CoV-2

TEMBEXA® transacted with Emergent BioSolutions

Smallpox (orphan drug designation)

APPROVED June 4, 2021

1

Malignant glioma

2 Adult recurrent H3 K27M-mutanthigh-grade glioma

4

3

H3 K27M-mutant glioma

4.

Central Nervous System

5.

Rapidly Emerging Antiviral Drug Development Initiative

ONC201 (dordaviprone) Phase 2 Efficacy Analysis

H3 K27M-mutant diffuse glioma: high unmet need

Frontline H3 K27M DMG2

Histone H3 Mutations

• H3 K27M mutation is predominantly found

in CNS Tumors1

among diffuse midline gliomas (DMGs) in

young adults and children

• Frontline radiotherapy remains standard of care with transient benefit; resection often not feasible

• 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

-

-

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 SAEs considered not related to ONC201 by sponsor

7

FDA-aligned criteria for Phase 2 efficacy analysis to isolate ONC201

single agent activity

Objective

  • To evaluate monotherapy efficacy of ONC201 in recurrent H3 K27M-mutant diffuse midline glioma
    Eligibility
  • Age ≥2yo and received ONC201 under studies ONC006, ONC013, ONC014, ONC016, or ONC018
  • Diffuse glioma with a known H3 K27M mutation and involvement of a midline structure of the brain
  • Progressive and measurable disease on contrast-enhanced brain MRI by RANO-High Grade Glioma (HGG) criteria
  • Prior therapy with at least radiation
  • Washouts prior to first ONC201 dose:
    • Radiation: 90 days
    • Temozolomide: 23 days / Antibodies (e.g., bevacizumab): 42 days / Other anticancer therapies: 28 days
  • Baseline Performance Status ≥60
  • Corticosteroids stable or decreasing for at least 3 days prior to baseline scan
  • Excluded: DIPG, primary spinal tumors, atypical and non-astrocytic hist., leptomeningeal spread, CSF dissemination

8

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

RANO LGG (non-enhancing)

  • 26% response
  • 42% 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)
  • Growing consensus that assessment of enhancing and non-enhancing disease (RANO- HGG and RANO-LGG criteria) is needed for diffuse midline glioma

9

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

PD=progressive disease

RANO-HGG responses observed across age groups

Responses by age group:

<18 years: 1/4 (25%)

18-40 years: 5/32 (16%)

>40 years: 4/14 (29%)

RANO-HGG response of 8-year-old subject suggests activity in this population

10

ONC201 Ph 2 Efficacy Analysis by BICR in Recurrent H3

K27M-mutant Diffuse Midline Glioma

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Chimerix Inc. published this content on 02 November 2023 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 02 November 2023 12:33:56 UTC.