#1Post Society for Neuro- Oncology Management Conference Call November 22, 2021 8° CHIMERIX O 2021 Chimerix, Inc#28 Forward-Looking Statements These slides 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 status of Chimerix's oncology programs, and the results of the 50- patient efficacy analysis of ONC201, including those related to the potential safety and benefit of ONC201 or the prevalence or severity of H3K27M mutant glioma. 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 clinical study data for ONC201 will not support accelerated, or any, regulatory approval; the anticipated benefits of the acquisition of Oncoceutics may not be realized; the ability to generate positive results in a Phase 3 study in acute myeloid leukemia and subsequent approval for DSTAT; risks that ongoing or future trials may not be successful or replicate previous trial results, or may not be predictive of real-world results or 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. 2 O 2021 Chimerix, Inc#3Clinical Efficacy of ONC201 in Recurrent H3 K27M- Mutant Diffuse Midline Glioma Patients Review: Society for Neuro-Oncology 2021 Presentation Isabel Arrillaga-Romany, MD, PhD Massachusetts General Hospital Boston, MA 3#4Diffuse Midline Glioma, H3 K27M-mutant Me he G34VIR Thalamus 4 G34V/R Pons Medulla oblongata G34V/R K27M K27M G34V/R Lulla et al., Science Advances, 2016 Fa G34V/R ● ● ● H3 K27M is detected in 50-90% of midline gliomas More prevalent in pediatric populations but also prevalent adults as well Highly aggressive malignancy; invariably lethal No effective drug therapies to date for recurrence No definite objective responses to systemic therapies by RANO HGG reported in literature in the recurrent setting Other midline sites- Thalamus. Pons Spinal cord. ● : 0 10 20 30 40 50 60 Patient age (years) Solomon et al., Brain Pathology 26 (2016) 569–580#5ONC201 Is a DRD2 Antagonist/ClpP Agonist 5 ClpP 12A ONC201 Mitochondria 17A Cytoplasm OXPHOS proteins Integrated stress response CHOP ATF4 DRD2 ERK AKT Cell death pathways Cell survival signals Dead cancer cell Selective killing of cancer cells Allen et al., Science Translational Medicine, 2013 Ishizawa et al, Science Signaling, 2016 Kline et al, Science Signaling, 2016 Siegelin et al, Clinical Cancer Research, 2018 Ishizawa et al, Cancer Cell, 2019 ONC201 Extracellular space Ras signaling pathways ● ● ● Oral small molecule Once weekly dosing based on pharmacodynamics Well tolerated DRD2 antagonist and ClpP agonist that induces tumor cell apoptosis#6Integrated Efficacy Analysis: Objective and Eligibility Criteria Objective To evaluate monotherapy efficacy of ONC201 in recurrent H3 K27M-mutant diffuse midline glioma Eligibility ● ● ● 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 260 ● Age 22yo and received ONC201 under studies ONC006, ONC013, ONC014, ONC016, or ONC018 Diffuse glioma with a known H3K27M 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 ● Corticosteroids stable or decreasing for at least 3 days prior to baseline scan Excluded: DIPG, primary spinal tumors, atypical and non-astrocytic histologies, leptomeningeal spread, CSF dissemination#7Endpoints 7 Primary Endpoint Overall response rate by RANO-HGG criteria Secondary Endpoints Overall response rate by RANO-Low Grade Glioma (LGG) criteria Duration of response¹ ● ● ● ● ● ● ● Time to response¹ Best overall response¹ Disease Control Rate¹ Progression-free survival¹ Overall survival Corticosteroid response rate Performance status response rate Analysis First 50 patient enrolled who meet eligibility for integrated efficacy analysis² ● Censored for all endpoints except overall survival upon eligibility criteria initiation of any additional anti-cancer therapy ¹Assessed by RANO-HGG and RANO-LGG criteria with dual-reader blinded independent central review (BICR). 2As discussed and prespecified with regulatory authorities#8● Response Assessment Criteria for Glioma DMG with H3K27M typically have both enhancing and non-enhancing disease components RANO-HGG responses defined by decrease in enhancing disease RANO LGG response defined by decrease in T2 FLAIR RANO- HGG Criterion T1-Gd+ T2/FLAIR New lesion Corticosteroids Clinical status Requirement for response 8 CR None Stable or ↓ None None Stable or ↑ All PR ≥50%↓ Stable or ↓ None Stable or ↓ Stable or ↑ All T2- FLAIR SD <50% to <25% ↑ Stable or ↓ None Stable or ↓ Stable or ↑ All T1-Gd+ PD ≥25% t ↑t Presentt NA+ ++ Any+ Zoom#9Response Assessment Criteria for Glioma ● RANO LGG response defined by decrease in T2 FLAIR RANO- LGG Criterion T2/FLAIR New lesion Corticosteroids Clinical status CR Disappearance of all lesions None (apart from those consistent with radiation effects, and no new or increased enhancement) None Stable or t Requirement for response All PR >50% in perpe dicular diameters of lesion, sustained for 4 weeks None (apart from those consistent with radiation effects, and no new or increased enhancement) Stable or ↓ Stable or t All T2- FLAIR MR 25-50% ↓ in perpendicular diameters of lesion None (apart from those consistent with radiation effects, and no new or increased enhancement) Stable or ↓ Stable or t All SD <25% to 25% T1-Gd+ None (apart from those consistent with radiation effects, and no new or increased enhancement) Stable or ↓ Stable or t All PD ≥25% t Present Zoom F NA ‡ ↓t (not attributable to other causes apart from the tumor, or decrease in corticosteroid dose) Any‡#10Patient Demographics and Disease Characteristics Age (years), median (range) <18 years, N(%) 18 - <40 years, N(%) >40 years, N(%) Gender, N(%) Male Female Race, N(%) White Other Black Asian Not reported Body weight (kg), median (range) Performance status (KPS/LPS), N(%) 60-70 80 90-100 10 N=50 30 (870) 4 (8%) 32 (64%) 14 (28%) 27 (54%) 23 (46%) 39 (78%) 6 (12%) 3 (6%) 1 (2%) 1 (2%) 88 (29 - 199) 14 (28%) 20 (40%) 16 (32%) ¹Multifocal disease includes non-target lesions ²Sum of product of diameters of enhancing target lesions per BICR Primary tumor location, N(%) Thalamic Other midline Multifocal disease¹, N(%) >1 Target lesion, N(%) Tumor size² (cm2), median (range) H3 K27M detection method IHC, N(%) NGS, N(%) First recurrence, N(%) Prior temozolomide, N(%) Time from recurrence, days, median (range) Time from prior radiation, months, median (range) Time from initial diagnosis, months, median (range) Daily steroid dose (mg, dex equiv): median (range) N=50 33 (66%) 17 (34%) 23 (46%) 9 (18%) 10.4 (1.640.8) 47 (94%) 3 (6%) 37 (74%) 44 (88%) 20 (1 126) 7.5 (3104) 10.9 (5-105) 1.1 (0.0 12.0)#11● ● Dosing & Disposition Dosing Oral 625 mg ONC201 (scaled by body weight for pediatric patients) Once every week with exception of one patient dosed once every 3 weeks Last patient enrolled February 26, 2020 Data cutoff for analysis May 31, 2021 Median follow-up 18.8 months - - Disposition Five patients remain on study drug; four patients continue post-progression - 11#12Serious Adverse Events 12 Any SAE¹ Gastrointestinal disorders Nausea Vomiting General disorders and administration site conditions Disease progression Nervous system disorders Brain oedema Encephalopathy Headache Respiratory, thoracic and mediastinal disorders Dyspnoea INTERNA Vascular disorders Embolism Pulmonary embolism Any attribution, N (%) 25 (50%) 2 (4%) 2 (4%) 2 (4%) 2 (4%) 4 (8%) 3 (6%) 2 (4%) 2 (4%) 2 (4%) ¹Specific preferred terms occurring in more than one patient are listed; 25 patients had at least one SAE ²Possibly related per investigator assessment; unlikely related per sponsor assessment Related, N (%) 1 (2%) 0 0 0 0 0 0 0 0 1 (2%)²#13Overall Response Rate (RANO-HGG) 13 RANO-HGG¹ ORR (CR + PR) Complete Response (CR) Partial Response (PR) Stable Disease (SD) Not Evaluable (NE)² Progressive Disease (PD) Not Applicable (NA)³ Disease Control Rate (CR + PR + SD) N=50 10 (20%) 95% CI: 10 - 34% 1 (2%) 9 (18%) 10 (20%) 8 (16%) 18 (36%) 4 (8%) 20 (40%) 95% CI: 26 – 55% ¹Integrated RANO HGG criteria assessment by dual reader BICR 2Five overall radiographic SD accompanied by increase in corticosteroids; 3 overall radiographic PD accompanied by decrease in corticosteroids ³Three patients did not have on-treatment monotherapy MRIs available for BICR; one patient censored prior to first on-treatment MRI#14Waterfall Plot (RANO-HGG) 14 Best % Change in SPD from Baseline * 100 75 50 25 -25 -50 -75 -100 * ||100. -000 ooo Change > 100%, CR=complete response, PR-partial response, SD=stable disease, NE=not evaluable, PD=progressive disease 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. PD NE SD PR CR 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.#15Spider Plot (RANO-HGG) 15 % Change in SPD from Baseline 100 75 50 25 O -25 -50 -75 -100 + H 3 6 + 9 + + 12 + 15 ONC201 ongoing, no other therapy initiated + New anticancer therapy initiated New lesion(s), first instance Duration of response, median (95% CI) Time to response, median (range) 18 21 24 Months from First Dose 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. 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. + 27 11.2 months (3.8 - not reached) 30 8.3 months (1.9 - 15.9) 33 36 + 39 42#16Overall Response Rate (RANO-LGG) RANO-LGG¹ ORR (CR + PR + MR) Complete Response (CR) Partial Response (PR) Minor Response (MR) Stable Disease (SD) Not Evaluable (NE) Progressive Disease (PD) Not Applicable (NA) Disease Control Rate (CR + PR + MR + SD) N=50 13 (26%) 95% CI: 15 - 40% 0 (0%) 6 (12%) 7 (14%) 8 (16%) 11 (22%)² 14 (28%) 4 (8%)³ 21 (42%) 95% CI: 28 - 57% 30.0% (95% CI: 17.9 - 44.6%) achieved an objective response by RANO-HGG and/or RANO-LGG criteria ¹ Integrated RANO LGG criteria assessment by dual reader BICR 2Eight overall radiographic SD accompanied by increase in corticosteroids; 3 overall radiographic PD accompanied by decrease in corticosteroids 16 ³Three patients did not have on-treatment monotherapy MRIs available for BICR; one patient censored prior to first on-treatment MRI#17Waterfall Plot (RANO-LGG) 17 Best % Change in SPD from Baseline * 100 75 50 25 0 -25 -50 -75 -100 000... U PD NE SDMR □ PR Change > 100%, PR-partial response, MR-minor response, SD=stable disease, NE=not evaluable, PD=progressive disease SPD=sum of products of perpendicular diameters (target non-enhancing lesions per BICR) Only patients with measurable target lesions by BICR at baseline and with post-baseline evaluations are included. Three patients did not have on-treatment monotherapy MRIs available for BICR; one patient censored prior to first on-treatment MRI. 00#18● ● Case Study Integrated Diagnosis: DMG, H3K27m mutation Molecular Features: MGMT promoter unmethylated, IDH wildtype. Significant response to treatment both by RANO- HGG and RANO-LGG by cycles 8 and 10; response was sustained for over one year 18 T1 POST Contrast FL Baseline LTH Cycle 8 Cycle 10#19Progression-Free Survival 19 Survival Probability 1.0 0.8 0.6 0.4 0.2 0.0 0 n 50 3 20 6 13 9 12 Months from First Dose 12 10 6 Months 12 Months 15 PFS (95% CI) 6 18 5 35% (21-49) 30% (17-44) 21 2 24 2#20Overall Survival 20 Survival Probability 1.0 0.8 0.6 0.4 0.2 0.0 0 n 50 OS overall survival 3 41 () 6 32 9 28 12 Months from First Dose 24 12 Months 24 Months 15 OS (95% CI) 18 18 14 57% (41-70) 35% (21 - 49) 21 11 24 9#21Performance Status and Corticosteroid Use 21 Corticosteroid Response¹ Evaluable, N Response rate, N(%) (95% CI) 15 7 (47%) (21 – 73%) Time to response, months median (range) Performance Status Response² Evaluable, N Response rate, N(%) (95% CI) Time to response, months median (range) 3.7 (1.9-5.6) 34 7 (21%) (9 - 38%) 3.5 (1.9 -22.4) Total Dex Dose (mg) 12 11 10 9 00 8 6 сл 4 3- 2 1 0 0 1 2 3 Corticosteroids³ 4 5 Months from First Dose 6 7 8 ¹Corticosteroid response: 250% reduction in average daily corticosteroid dose compared to baseline with stable or improved KPS/LPS. Must be confirmed at next analysis timepoint. Corticosteroids were converted into a dexamethasone equivalent dose. Baseline 24mg dexamethasone at baseline were evaluable. 2Performance status response: increase in KPS/LPS compared to baseline with stable or reduced corticosteroid use. Must be confirmed at next analysis timepoint. Baseline KPS/LPS ≤80 were evaluable. ³Average daily over 1 week around analysis window presented (every 8 weeks) 9#22● Summary Integrated response analysis results RANO-HGG criteria assessed by dual reader BICR ORR 20% (95% CI: 10 -34%) Median 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% (17-44) ● 22 ● ● ● ● RANO-LGG criteria assessed by dual reader BICR ORR 26% (95% CI: 15-40%) ● Overall survival ● ● 12 months: 57% (41-70%) 24 months: 35% (95% CI: 21 - 49%) ONC201 monotherapy exhibited apparent durable and clinically meaningful efficacy in recurrent H3 K27M- mutant DMG patients#23Acknowledgments 23 ● Children's National Medical Center Columbia University Andrew Lassman - Lindsay Kilburn Levine Cancer Inst (LCI) Ashley Sumrall - Miami Cancer Institute Yazmin Odia MD Anderson Cancer Center - Rebecca Harrison Nazanin Majd Dana Farber Cancer Inst Patrick Wen Tracy Batchelor Northwestern University Karan Dixit New York University Sylvia Kurz Sharon Gardner UCSF - - Nic Butowski Sabine Mueller University of Kansas Cancer Center Michael Salacz Anwaar Saeed University of Michigan Yoshie Umemura University of Minnesota Clark Chen University of Nebraska Nicole Shonka ● University of Washington Lynne Taylor Jerome Graber Washington University at St. Louis Karen Gauvain Sites, investigators, staff and patients across all the ONC201 glioma programs Chimerix; Oncoceutics Funding Partners NCI SBIR - Cancer Commons Michael Mosier Defeat DIPG Foundation The Musella Foundation The Cure Starts Now Foundation xCures#24Supplemental Material and Management Discussion CHIMERIX O 2021 Chimerix, Inc#25✓ ● ● 25 H3 K27M-mutant DMG is a grade IV by WHO FDA has acknowledged available therapy is palliative Often not possible to resect Recurrence inevitable after first-line radiation - Recurrent Glioma Remains a High Unmet Need - Chemotherapy ineffective; objective responses by RANO-HGG have not been reported Survival in grade II-IV recurrent glioma reported to be 27.5% at 12 months¹ and 6.4% at 24 months² Survival in pediatric recurrent H3 K27M DMG reported to be 0% at 24 months³ Survival in ONC201-treated recurrent H3 K27M DMG was 57% OS at 12 months and 35% at 24 months Survival Probability (%) 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Recurrent glioma historic survival 0.6 Coocoon 27.5% OS at 12 Months¹ Survival Probability (%) 0.5 Grade II-III Glioma 0.4 0.3 0.2 0.1 0.0 6.4% OS at 24 Months² GBM (Grade IV) 1. Data collected from 15 literature sources since 2010 with trial arms size >30 pts each reporting data on 1816 pts with recurrent, unstratified disease. 2. 10 literature sources that describes OS with 1279 patients 3. Koschmann et al, 2020; DOI:10.21203/rs.3.rs-69706/v1 O 2021 Chimerix, Inc#26✓ Waterfall Plot (RANO- HGG) Stratified by Performance Status ● ● 26 Expectedly, patients with higher PS were more likely to respond to treatment 100: 1/2 (50%) 90: 4/14 (29%) 80: 4/20 (20%) - 70: 1/7 (14%) 60: 0/7 (0%) - Consistent with hypothesis that treating earlier in disease course may enhance efficacy Best % Change in SPD from Baseline 100 75 50 25 O -25 -50 -75 -100 T 1110 * Change > 100%, SPD-sum of products of perpendicular diameters (target enhancing lesions per BICR) Only patients with measurable target enhancing lesions at both baseline and post-baseline are included. 060 ☐ 070 080 090 ☐ 100 © 2021 Chimerix, Inc#278 Waterfall Plot (RANO- HGG) Stratified by Age Responses observed across age groups: <18 years: 1/4 (25%) 18-40 years: 5/32 (16%) >40 years: 4/14 (29%) RANO-HGG response of 8-year- old subject confirms activity in this population - 27 Best % Change in SPD from Baseline 100 75 50- 25 O -25 -50 -75 -100 * Change > 100%, SPD-sum of products of perpendicular diameters (target enhancing lesions per BICR) Only patients with measurable target enhancing lesions at both baseline and post-baseline are included. 18-<40 ☐ <18 240 O 2021 Chimerix, Inc#28✓ Pediatric Case Study 8-year-old thalamic H3.3 K27M DMG initially diagnosed in May 2018 First-line therapy: radiation, dasatinib, everolimus and bevacizumab Second-line therapy: 375mg weekly ONC201 monotherapy initiated Apr 2019 following progression on first-line therapy Clinical and radiographic improvement over >2 years of therapy PS: absolute value Tumor size: % change from baseline 28 100 80 60 40 20 0 0 3 6 וכ T 12 Months from First Dose 15 Performance Status (PS) Tumor Size T 18 21 24 Pre-ONC201 baseline 9 months on ONC201 18 months on ONC201 O 2021 Chimerix, Inc#29Adult Case Study • 54-year-old thalamic H3 K27M DMG diagnosed in Nov 2018 First-line therapy: radiation and temozolomide ● ● Second-line therapy: 625mg weekly ONC201 monotherapy initiated May 2019 Corticosteroid elimination and radiographic regression over >1.5 years of therapy PS: absolute value Tumor size: % change from baseline Corticosteroid use: % change from baseline 29 100 80 60 40 20 0 0 3 Corticosteroid Use 6 9 Months from First Dose 12 Performance Status Tumor Size 15 18 Pre-ONC201 baseline 12.9 months on ONC201 18.5 months on ONC201 © 2021 Chimerix, Inc#30● ✓ ONC201 Activity in Non-Midline H3 K27M Diffuse Glioma Two of five patients had objective responses by RANO-HGG per investigator but not BICR¹ Both patients had a response by RANO-LGG per BICR o Patients were on-treatment for 14 and 23 months Responses were associated with increased mobility and alertness Suggest activity may not be restricted by location 30 Change from baseline in SPD (%) 100 - 75 50 - 25 0 -25 -50 -75- -100 0 T 1 Measured by RANO HGG² 3 5 6 7 Time from first dose (mo) 8 9 10 11 12 13 14 15 16 17 18 1. Odia et al, SNO 2021 2. One of these five patients did not have a measurable lesion per BICR Change from baseline in SPD (%) 100 75- 50 -50 -75- -100 T Measured by RANO LGG T T 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Time from first dose (mo) O 2021 Chimerix, Inc#31N RANO Responses Correspond with Survival & Clinical Benefit RANO HGG and/or LGG Responders 15 PFS at 12 months (number of patients censored) OS at 24 months (number of patients censored)² Corticosteroids response³ (number of patients evaluable) Performance status response4 (number of patients evaluable) ✓ All patients 50 30%¹ 35%1 47% (15) 21% (34) RANO HGG Responders 10 90% (0) 80% (2) 100% (4) 60% (5) 67% (2) 53% (5) 100% (5) 67% (9) All Other Patients 35 0% (8) 0% (8) 20% (10) 4% (25) 1. Kaplan-Meier median Progression-Free Survival or Overall Survival 2. Censored patients include those who are lost to follow-up or have withdrawn prior to the time point, as well as those who have not yet reached the time point. These patients are counted in the denominator but not counted as survivors (i.e., imputed as failure) 3. Corticosteroid response: ≥50% reduction in average daily corticosteroid dose compared to baseline with stable or improved KPS/LPS. Must be confirmed at next analysis timepoint. Corticosteroids were converted into a dexamethasone equivalent dose. Baseline 24mg dexamethasone at baseline were evaluable. 4. Performance status response: increase in KPS/LPS compared to baseline with stable or reduced corticosteroid use. Must be confirmed at next analysis 31 timepoint. Baseline KPS/LPS ≤80 were evaluable. © 2021 Chimerix, Inc#32Summary ONC201 monotherapy exhibited durable and clinically meaningful efficacy in recurrent H3 K27M-mutant DMG patients - RANO-HGG criteria assessed by dual reader BICR ORR 20% (95% CI: 10-34%) 32 ● ● ● RANO-LGG criteria assessed by dual reader BICR ORR 26% (95% CI: 15-40%) Median 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%) 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 One SAE was considered possibly related to ONC201 by investigator and unlikely related to ONC201 by sponsor O 2021 Chimerix, Inc