FALSE000111748000011174802024-12-092024-12-09

UNITED STATES
 
SECURITIES AND EXCHANGE COMMISSION
 
Washington, DC 20549
 
FORM 8-K
 
CURRENT REPORT
 
Pursuant to Section 13 or 15(d)
of The Securities Exchange Act of 1934
 
Date of Report (Date of earliest event reported): December 9, 2024

Chimerix, Inc.
(Exact name of registrant as specified in its charter)
 
Delaware 001-35867 33-0903395
(State or other jurisdiction of incorporation) (Commission File Number) (IRS Employer Identification No.)
 
2505 Meridian Parkway, Suite 100
Durham, NC
 27713
(Address of principal executive offices) (Zip Code)
 
(919) 806-1074
(Registrant’s telephone number, including area code)

N/A
(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions: 
☐Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) 
☐Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
☐Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
☐Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
 
Securities registered pursuant to Section 12(b) of the Act:
Title of each classTrading Symbol(s)Name of each exchange on which registered
Common Stock, par value $0.001 per shareCMRXThe Nasdaq Global Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨





Item 7.01 Regulation FD Disclosure.

On December 10, 2024, Chimerix, Inc. (the “Company”) made available an updated corporate presentation (the “Presentation”) that the Company intends to use, in whole or in part, in meetings with investors, analysts and others. The Presentation can be accessed through the “Investors” section of the Company’s website. A copy of the Presentation is furnished as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated by reference herein.

The information in this Item 7.01 and the attached Exhibit 99.1 is being furnished and shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that Section. The information in this Item 7.01 and the attached Exhibit 99.1 shall not be incorporated by reference into any registration statement or other document pursuant to the Securities Act of 1933, as amended.

Item 8.01 Other Events.

On December 9, 2024, the Company announced its plan to submit a complete new drug application (“NDA”) seeking accelerated approval for dordaviprone (“ONC201”) as a treatment for recurrent H3 K27M-mutant diffuse glioma in the United States before year-end 2024, following extensive dialogue with the U.S. Food and Drug Administration (the “FDA”). ONC201 is a novel first-in-class small molecule imipridone that selectively targets the mitochondrial protease ClpP and dopamine receptor D2 (“DRD2”), which has received Rare Pediatric Disease Designation for H3 K27M-mutant glioma and is eligible to apply for a Rare Pediatric Disease Priority Review Voucher (“PRV”). The Company intends to apply for a Rare Pediatric Disease PRV in the upcoming NDA submission.

The following recent program milestones and additional supportive data were extensively discussed with the FDA and will be included in the NDA:

•Substantial enrollment of the Phase 3 ACTION study;
•Phase 2 objective response rate of the 50-patient primary efficacy analysis assessed by blinded independent central review as the primary basis of efficacy in the NDA;
•Several response assessments, including the most contemporary response assessment criteria for gliomas, Response Assessment in Neuro-Oncology 2.0 (“RANO 2.0”), under which ONC201 demonstrated an objective response rate of 28%, a median duration of response of 10.4 months and a median time to response of 4.6 months;
•Additional clinical data sets and patient narratives supportive of the primary efficacy analysis observed to date;
•Clinical and nonclinical demonstration of dordaviprone-driven reversal of the central hallmark of H3 K27M-mutant glioma, H3K27 trimethyl loss;
•Comprehensive safety database of glioma patients and healthy volunteers that supports a favorable benefit/risk profile observed to date; and
•Comprehensive clinical pharmacology and chemistry, manufacturing, and controls studies.

The Company will request Priority Review for the NDA. If granted, the resulting six-month FDA review period is expected to result in a potential initial Prescription Drug User Fee Act (“PDUFA”) action date for accelerated approval in the third quarter of 2025.

Should the Company be awarded a Rare Pediatric Disease PRV and thereafter sell such Rare Pediatric Disease PRV to a third party, 50% of the net proceeds from such sale would be payable to the former securityholders of Oncoceutics, Inc. pursuant to the Agreement and Plan of Merger with Oncoceutics, Inc., dated as of January 7, 2021.

In addition, the Company expects to determine by early 2025 the recommended dosing for planned Phase 2 clinical trials of ONC206. ONC206 is a second generation ClpP agonist and DRD2 antagonist that has demonstrated monotherapy anti-cancer activity in non-clinical models and is currently in dose escalating clinical trials for adult and pediatric patients with primary central nervous system tumors.

Forward-Looking Statements

The Company cautions you that statements included in this report that are not a description of historical facts are forward-looking statements. Words such as “anticipate,” “expect,” “intend,” “plan,” “believe,” “seek,” “estimate,” “will,” “should,” “would,” “could,” “may” and similar expressions also identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding the possible regulatory path forward for dordaviprone, including the potential to seek accelerated approval, priority review, rare pediatric disease priority review vouchers and approval for marketing


authorization; timing and consequences of an NDA submission to FDA; FDA’s acceptance for filings; the timeline of related discussions with the FDA; the initial potential PDUFA timing; the potential commercial opportunity; the ability of dordaviprone to attain significant market acceptance among disease experts, patient advocates and their patients; the expected impact of dordaviprone on patients; expectations regarding interim OS data from the Phase 3 ACTION study of dordaviprone; plans for provisional registration and commercialization in Australia; expectations regarding our international market opportunities; expectations regarding completion of enrollment and assessment of responses in the ONC206 dose escalation trials; and the timing, characteristics and development of ONC206. The inclusion of forward-looking statements should not be regarded as a representation by the Company that any of these results will be achieved. Actual results may differ from those set forth in this report due to the risks and uncertainties associated with market conditions and our cash runway; risks related to the ability to obtain and maintain accelerated approval, priority review, rare pediatric disease priority review vouchers, and approval for marketing authorization; risks related to the timing, completion and outcome of the Phase 3 ACTION study of dordaviprone; uncertainty on the response of regulators to including additional supportive data to be submitted in the NDA filing, including RANO 2.0 assessments, and uncertainty with respect to the initial potential PDUFA timing; risks related to the clinical development of ONC206; risks associated with market acceptance; risks associated with repeating positive results obtained in prior preclinical or clinical studies in future studies; risks related to the clinical development of our clinical candidates; and additional risks and uncertainties inherent in the Company’s business, including those described in the Company’s filings with the Securities Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and the Company undertakes no obligation to revise or update this report to reflect events or circumstances after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.

Item 9.01Financial Statements and Exhibits.
 
(d)Exhibits
Exhibit No. Description
99.1
104Cover Page Interactive Data File (embedded within the Inline XBRL document).
 





SIGNATURES
 
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
 
 Chimerix, Inc.
   
Date: December 10, 2024  
  By:/s/ Michelle LaSpaluto
  Name:Michelle LaSpaluto
  Title:Chief Financial Officer

 
 



Chimerix Corporate Presentation December 10, 2024

 
2 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 possible regulatory path forward for dordaviprone, including the potential to seek accelerated approval, priority review, rare pediatric disease priority review vouchers and approval for marketing authorization; timing and consequences of a new drug application (NDA) submission to FDA; FDA’s acceptance for filings; the timeline of related discussions with the FDA; the initial Prescription Drug User Fee Act (PDUFA) timing; the ability of dordaviprone to attain significant market acceptance among disease experts, patient advocates and their parents; the expected impact of dordaviprone on patients; expectations regarding interim OS data from the ACTION study; expectations regarding completion of enrollment and assessment of responses in the ONC206 dose escalation trials; the characteristics and development of our product candidates; 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 ability to obtain and maintain accelerated approval, a priority review, rare pediatric disease priority review vouchers, and approval for marketing authorization; uncertainty on the response of regulators to including additional supportive data to be submitted in the NDA filing, including RANO 2.0 assessments, and uncertainty with respect to the initial potential PDUFA timing; risks related to the timing, completion and outcome of the Phase 3 ACTION study of dordaviprone; risks associated with repeating positive results obtained in prior preclinical or clinical studies in future studies; risks related to the clinical development of ONC206; risks associated with the potential market opportunity, funding and timing of future data readouts for our products; 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.

 
3 Investment Highlights and Key Catalysts Dordaviprone U.S. NDA submission planned for Dec ‘24, potential U.S. accelerated approval in 2025  No approved therapies currently in recurrent H3 K27M diffuse glioma, an invariably lethal Grade 4 glioma (World Health Org)  Total addressable market exceeds $1Bn in U.S. (U.S. incidence >2,000 patients, ultra-orphan drug pricing)  Patent protection thru 2037 (potential additional U.S. patent term extension)  Front-line Ph 3 trial (ACTION study) substantial enrollment, active in >150 sites and 17 countries  Application for Rare Pediatric Disease Priority Review Voucher (PRV) to be included in upcoming NDA ONC206 Recommended Phase 2 dose expected early 2025  Pharmacokinetic data from dose escalation studies demonstrate dose proportionate exposure  No unexpected safety events and no dose limiting toxicities to date  Exhibits monotherapy activity in multiple non-clinical CNS models as well as tumors outside the CNS $152 million in capital to fund operations as of September 30, 2024 Positioned to accelerate growth from internal and/or external innovation  Robust business development search and evaluation process Planned NDA submission in December 2024 Potential accelerated approval in Q3 2025 Imipridone pipeline progressing

 
4 Program Preclinical Phase 1 Phase 2 Registrational Regulatory Approval Deep Pipeline Across All Development Stages Dordaviprone (ONC201) Front line (ACTION study) H3 K27M-mutant diffuse glioma IITs- multiple oncology studies CMX521 Novel coronaviruses Central Nervous System tumors ONC206 IND-enabling studies ONC212 TEMBEXA® transacted with Emergent BioSolutions Smallpox (orphan drug designation) Other solid tumors Recurrent H3 K27M-mutant diffuse glioma

 
Dordaviprone: H3 K27M-mutant diffuse glioma

 
6 • Highly aggressive and classified as WHO Grade 4 • U.S. incidence >2,000 - most frequently occurs in children and young adults1 • Surgical resection limited due to location • Effective treatment limited to radiotherapy, invariably recurs • No approved therapies for H3 K27M-mutant glioma currently • Median overall survival approximately 1 year2 from diagnosis and 5.1 months3 from recurrence About H3 K27M-mutant Diffuse Glioma 1ZS Associates, ONC201 Opportunity Assessment – Epidemiology Assumptions, October 31, 2024 2Vuong et al, Frontiers in Oncology March 2022. 3 Company-sponsored natural disease history study. 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) 4 see slide 18 for supporting references Thalamic (52%) Pineal (20%) Cerebellum (22%) Brainstem (excluding pons) (50%) Non-midline (~2%) Ventricle (71%) Pons (75%) Spinal cord (49%) H3 K27M-mutant Patients by Tumor Location (rate of positivity)4

 
7 Recent program milestones include: • Substantial enrollment of the Phase 3 ACTION study • 50-patient primary efficacy analysis using multiple response criteria, including the most recently established response criteria for glioma, Response Assessment in Neuro Oncology (RANO) 2.0 • Responders had consistent findings in other measures of clinical benefit, including reduction in corticosteroid dose, improvement in performance status, and longer survival • Additional clinical data sets and patient narratives supportive of the primary efficacy analysis observed to date • Clinical and nonclinical demonstration that dordaviprone reverses the central hallmark of H3 K27M- mutant diffuse glioma: H3 K27 trimethyl loss • A comprehensive safety database of glioma patients treated with dordaviprone which supports a favorable benefit/risk profile observed to date • Comprehensive clinical pharmacology and Chemistry, manufacturing, and controls (CMC) studies We Believe Extensive Program Progress Supports New Drug Application Seeking U.S. FDA Accelerated Approval

 
8 Objective • To evaluate monotherapy efficacy of dordaviprone in recurrent H3 K27M-mutant diffuse midline glioma by dual-reader blinded independent central review (BICR) in first 50 subjects who meet the following eligibility criteria agreed to with U.S. FDA Eligibility • Age ≥2yo and received dordaviprone 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 • Washouts prior to first dordaviprone 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 Eligibility for Primary Efficacy Analysis Aligned With FDA

 
9 n=50 RANO 2.0 RANO-HGG RANO-LGG Objective Response Rate, n (%) [95% CI] 14 (28.0) [16.2-42.5] 10 (20.0) [10.0-33.7] 13 (26.0) [14.6-40.3] Complete Response 0 1 (2.0) 0 Partial Response 10 (20.0) 9 (18.0) 6 (12.0) Minor Response 4 (8.0) NA 7 (14.0) Stable Disease 6 (12.0)1 10 (20.0) 8 (16.0) Not Evaluable 11 (22.0) 8 (16.0)2 11 (22.0)3 Progressive Disease 15 (30.0) 18 (36.0) 14 (28.0) Not Applicable 4 (8.0) 4 (8.0) 4 (8.0) Disease Control Rate, n (%) [95% CI] 20 (40.0) [26.4-54.8] 20 (40.0) [26.4-54.8] 21 (42.0) [28.2-56.8] Median Time to Response, months [range] 4.6 [1.6-15.9] 8.3 [1.9-15.9] 3.6 [1.6-17.8] Median Duration of Response, months, [95% CI] 10.4 [7.4-15.4] 11.2 [3.8-NR] 10.4 [3.6-12.7] Overall Survival, months, median [95% CI] 14.0 [8.0-26.1] 12-month survival estimate, [95% CI] 57.5% [41.7-70.5] 24-month survival estimate, [95% CI] 37.6% [23.2-51.9] 1.Includes one patient with unconfirmed response by RANO 2.0. 2.Five overall radiographic SD accompanied by increase in corticosteroids; three overall radiographic PD accompanied by decrease in corticosteroids. 3.Eight overall radiographic SD accompanied by increase in corticosteroids; three overall radiographic PD accompanied by decrease in corticosteroids. Primary Efficacy Analysis in Recurrent H3 K27M-mutant DMG by dual reader BICR

 
10 RANO 2.0 response as a time varying covariate was significantly associated with OS in a multivariate Cox Proportional Hazards model (HR [95% CI]: 0.22 [0.08 to 0.58]; p=0.0024) 1Best overall response by RANO criteria assessed by BICR. Not evaluable if PD with decreasing steroids or SD with increasing steroids. Not applicable if no post-baseline assessments. 2Progression free-survival ≥ 6 months / 12 months by RANO 2.0 criteria assessed by BICR; Overall survival ≥ 12 months / 24 months. Patients censored if not progressed/alive at last assessment/follow-up prior to cutoff. 3Performance status response defined as increase in KPS/LPS compared with baseline, while also having stable or reduced corticosteroid use. Increase must be confirmed at the next analysis timepoint. Patients with baseline KPS/LPS ≤80 were evaluable for this analysis. 4Corticosteroid response defined as ≥50% reduction in average daily steroid dose compared with baseline or reduction ≤2 mg with stable or improved KPS/LPS. Reduction must be confirmed at the next analysis timepoint. Corticosteroids were converted into a dexamethasone equivalent dose. Patients receiving ≥4mg dexamethasone at baseline were evaluable for this analysis. Primary Efficacy Analysis ‘Heatmap’ Reflects RANO Responses Associated with Other Measures of Clinical Benefit RANO 2.01 RANO-HGG1 RANO-LGG1 PFS62 PFS122 PS Response3 Steroid response4 OS122 OS242 Complete response Partial response Minor Response Stable Disease Not Evaluable Progressive Disease Not Applicable Yes No Censored Yes No Unevaluable Yes No Unevaluable RANO1 PFS6 / PFS12 / OS12 / OS242 Performance Status Response3 Steroid Response4 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 Legend Patients

 
11 * Change > 100%, PR=partial response, MR=minor response, SD=stable disease, NE=not evaluable, PD=progressive disease MRI type: T1 post-contrast1 MRI type: T2/FLAIR1 RANO 2.0 RANO 2.0 28% ORR by RANO 2.0 Evaluates Enhancing and Non-Enhancing Disease 1 50-patient primary efficacy analysis in recurrent H3 K27M-mutant DMG by dual-reader BICR: Chimerix internal analysis as of December 9, 2024 Reflects Only Enhancing Disease Includes Non-Enhancing Disease

 
12 Clinical Pharmacology Studies n=245 • Dordaviprone 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. • Dordaviprone clinical pharmacology program includes: - Dose-escalation, food-effect, & formulation evaluation - Thorough QT Study - Drug-drug interaction (DDI) studies: Strong CYP3A4 inhibitor and Proton-pump inhibitor studies - Renal impairment study - Hepatic impairment study - Mass balance study - Formulation Bioequivalence studies Robust Dordaviprone Clinical Pharmacology and Safety Assessment Supported Favorable Benefit/Risk Profile Glioma Patient Studies Treatment-related Adverse Events in >5% 1. Based on available data from dordaviprone Investigator brochure, version 11, AEs are prior to initiation of other anticancer therapy Treatment-related Adverse Events, Integrated Safety Data Set, (N=422 glioma patients) 1 Related TEAEs All grades Grade > 3 Any Treatment-related AE 51.4% 9.7% Fatigue 18.5% 1.7% Nausea 14.5% 0 Vomiting 10.4% 0.9% Lymphocyte count decreased 8.1% 1.9% Headache 6.6% 0 ALT increased 6.4% 0.7% White blood cell count decreased 5.5% 0.2% Only 10 patients (2.4%) experienced a treatment-related AE that led to study drug modification or discontinuation.

 
13 Dordaviprone FDA Designations 1. Should the Company be awarded a Priority Review Voucher and thereafter sell such Priority Review Voucher to a third party, 50% of the net proceeds from such sale would be payable to the former security holders of Oncoceutics, Inc., pursuant the Agreement and Plan Merger, dated January 7, 2021. Rare Pediatric Disease Designation for treatment of H3 K27M mutant glioma - Upcoming NDA to include an application for a Rare Pediatric Disease Priority Review Voucher1 Orphan Drug Designation Fast Track Designation

 
Dordaviprone Phase 3 ACTION Study Summary

 
15 Now enrolling, a randomized, double-blind, placebo-controlled, multicenter international study in 450 newly diagnosed diffuse glioma patients whose tumor harbors an H3 K27M-mutation Pivotal Phase 3 ACTION Trial Design 1. Excludes DIPG and spinal tumors • H3 K27M-mutant diffuse glioma1 • Radiation therapy recently completed • KPS > 70 at time of randomization • Stable steroid dose • No prior bevacizumab • No temozolomide within three weeks Dordaviprone twice weekly (625mg ONC201 day 1 + day 2) Dordaviprone weekly (625mg ONC201 day 1 + placebo day 2) Placebo (Placebo day 1 + placebo day 2) • Primary: Overall Survival • PFS (alpha-allocated) • Secondary: steroid response, performance status, QoL, neurologic function Key Patient Inclusion EndpointsTreatment

 
16 We Believe the ACTION Study Design Provides Multiple Paths for Success Interim data expected in third quarter of 2025 Second OS Interim • ~246 events • Success at HR~0.64 Final OS • ~327 events • Success at HR~0.73 PFS by RANO HGG(2) • ~286 events • Success at HR~0.68 1. Overall Survival (OS) 2. Progression-free survival (PFS). PFS may provide valuable data for regulatory discussions. 3. Hazard Ratio Independent comparisons for each dordaviprone arm versus control will be made at each timepoint Powering assumptions 0.65 expected HR for OS and 0.60 expected HR for PFS First OS(1) Interim • ~164 events • Success at HR(3)~0.52

 
Dordaviprone Market Opportunity Assessment

 
18 (1) Ostrom QT, et al. Neuro Oncol. 2022;24(Suppl 5):v1-v95; (2) Patient numbers and percentages are estimates (weighted avg per sample size) derived from a review of the literature from (2012-2023): (Aihara K, et al. Neuro Oncol. 2014;16(1):140-6; Feng J, et al. Hum Pathol. 2015;46(11):1626-32; Solomon DA, et al. Brain Pathol. 2016;26(5):569-80;Ryall S, et al. Acta Neuropathol Commun. 2016;4(1):93; Aboian MS, et al. AJNR Am J Neuroradiol. 2017;38(4):795-800; Wang L, et al. Hum Pathol. 2018;78:89-96; Castel D, et al. Acta Neuropathol Commun. 2018;6(1):117; Karremann M, et al. Neuro Oncol. 2018;20(1):123-131; Aboian MS, et al. AJNR Am J Neuroradiol. 2019;40(11):1804-1810; Dorfer C, et al. Acta Neurochir (Wien). 2021;163(7):2025-2035; Sievers P, et al. Neuro Oncol. 2021;23(1):34-43; Mackay A, et al. Cancer Cell. 2017;32(4):520-537 e5; Huang T, et al. Oncotarget. 2018;9(98):37112-37124; Schreck KC, et al. J Neurooncol. 2019;143(1):87-93; Chiba K, et al. World Neurosurg. 2020;134:e530-e539; Mukasa A, et al. Neuro Oncol. 2014;16(Suppl 3):iii9-iii10; Castel D, et al. Acta Neuropathol. 2015;130(6):815-27; Khuong-Quang DA, et al. Acta Neuropathol. 2012;124(3):439-47; Roux A, et al. Neuro Oncol. 2020;22(8):1190-1202; Giagnacovo M, et al. Childs Nerv Syst. 2020;36(4):697-704; Wu G, et al. Nat Genet. 2014;46(5):444-450; Wu G, et al. Nat Genet. 2012;44(3):251-3; Taylor KR, et al. Nat Genet. 2014;46(5):457-461; Saratsis AM, et al. Acta Neuropathol. 2014;127(6):881-95; Erker C, et al. Neuro Oncol. 2022;24(1):141-152; Buczkowicz P, et al. Acta Neuropathol. 2014;128(4):573-81; Daoud EV, et al. J Neuropathol Exp Neurol. 2018;77(4):302-311; Chai RC, et al. Acta Neuropathol Commun. 2020;8(1):40; Yi S, et al. Neurosurgery. 2019;84(5):1072-1081; Gessi M, et al. Acta Neuropathol. 2015;130(3):435-7; Alvi MA, et al. Mod Pathol. 2019;32(9):1236-1243; Crotty EE, et al. J Neurooncol. 2020;148(3):607-617; Dono A, et al. J Clin Neurosci. 2020;82(Pt A):1-8; Akinduro OO, et al. J Neurosurg Spine. 2021;35(6):834-843; Nakata S, et al. Brain Tumor Pathol. 2017;34(3):113-119; Nomura M, et al. Acta Neuropathol. 2017;134(6):941-956; Eschbacher KL, et al. Am J Surg Pathol. 2021;45(8):1082-1090; D'Amico RS, et al. J Neurooncol. 2018;140(1):63-73; Korshunov A, et al. Acta Neuropathol. 2015;129(5):669-78; Aibaidula A, et al. Neuro Oncol. 2017;19(10):1327-1337.) (3) ZS Associates, ONC201 Opportunity Assessment – Epidemiology Assumptins, October 31, 2024 • ~40% of 4,000+ midline gliomas are expected to harbor the H3 K27M mutation2 • ~2% of 17,000+ non-midline gliomas are expected to harbor the H3 K27M mutation2 • Each year it is estimated that ~2,000 patients are affected by H3 K27M-mutant glioma in the U.S;3 ~5,000 patients in the top seven global markets (by extrapolation of the estimated US incidence rate to the top seven markets) • No approved therapies specifically for H3 K27M mutant glioma currently Thalamic 220 patients (52%) Pineal 40 patients (20%) Cerebellum 240 patients (22%) Brainstem (excluding pons) 270 patients (50%) Non-midline ~350 patients (~2%) Ventricle 250 patients (71%) Pons 290 patients (75%) Spinal cord 370 patients (49%) Approximately 21,000 gliomas reported in the U.S. each year, affecting all locations in the brain1 Estimated # of U.S. H3 K27M+ Patients by Tumor Location (rate of positivity)2

 
19 Commercial Platform Expected to be Ready for Launch by Q3 2025, if NDA is Granted Unmet Need Patient Advocacy Patient Services & Distribution Access & Pricing Functional Expertise • Commercial Operations • Analytics & Insights • Pricing & Access • Distribution & Services • Marketing • Sales • Ultra-Orphan pricing • Protected Class status • Payer Engagement • Third Party Logistics • Specialty Pharmacy • Industry leading patient services • Lethal condition with limited treatment options • Predominately affects children and young adults • >2,000 US patients         Work initiated • Collaborative engagements 

 
20 Specialized account teams embracing the patient community Focused efforts on concentrated centers of excellence and KOLs Optimized promotional effort throughout the neuro-oncology ecosystem Data-driven approach to drive investments and maximize effectiveness Scalable and flexible infrastructure to ensure long-term sustainability Launch Plan Will Be Enabled by a Focused and Agile Commercial Infrastructure Leveraging brand equity and deep expertise within the Neuro-oncology community 66 U.S. ACTION sites and 25 U.S. EAP sites Strong support and pre-launch engagement from Neuro-Oncology Centers of Excellence U.S. sites active as of December 9, 2024

 
Dordaviprone Mechanism of ActionDordaviprone Mechanism of Action

 
22 • Dordaviprone can selectively induce apoptosis in cancer cells by altering the activity of two protein targets1 • ClpP agonism - Dordaviprone modifies ClpP conformation to increase degradation of mitochondrial proteins important for metabolism, epigenetics, and cancer cell viability • DRD2 antagonism - DRD2 is a G protein-coupled neuroreceptor that regulates Ras signaling - Dordaviprone antagonizes DRD2, inhibiting Ras signaling pathways Dordaviprone Directly Engages ClpP and DRD2 Dordaviprone upregulates integrated stress response, inactivates Akt/ERK, and selectively induces tumor cell death 1. https://pubmed.ncbi.nlm.nih.gov/38386699/. ClpP=caseinolytic protease P; OXPHOS=oxidative phosphorylation; DRD2=Dopamine receptor D2; ATF4=activating transcription factor 4; CHOP=C/EBP-homologous protein; ERK=extracellular-regulated kinase;

 
23 Dordaviprone Reverses Central Hallmark of H3 K27M-mutant Diffuse Glioma Mitochondrial effects of dordaviprone reverse H3 K27me3-loss Statistically significant H3 K27me3-loss reversal in dordaviprone-treated H3 K27M diffuse glioma patients https://aacrjournals.org/cancerdiscovery/article/13/11/2370/729854/Clinical-Efficacy-of-ONC201-in-H3K27M-Mutant Venneti S., et al

 
ONC206

 
25 • 10x higher in vitro potency relative to dordaviprone • Monotherapy efficacy data observed across multiple preclinical models of Central Nervous System (CNS) and non-CNS tumors • Tumor regression in patient-derived xenografts • Oral dose escalation trials with intensified dosing nearing completion in CNS cancers ONC206: Second Generation Oral Brain Penetrant ClpP Agonist + DRD2 Antagonist 1. PDB 6CM4 2. PDB 6DL7 DRD21 ClpP2 ONC206

 
26 0 100 200 300 400 500 600 700 800 900 1000 1100 1200 1 2 3 4 5 6 7 8 9 10 11 O N C 20 6 m g/ w ee k Dose level 50 m g BI D 15 0 m g Q D 10 0 m g BI D 15 0 m g BI D 20 0 m g BI D 3 Once weekly dosing 3 consecutive days dosing 3 ONC206 Ph 1 Dose Escalation in Unselected CNS Tumors Enrolling Final Cohort1,2 1. In partnership with Nation al Institutes of Health (NIH) 2. In partnership with Pacific Pediatric Neuro-Oncology Consortium (PNOC) 3. In adults only Recommended Phase 2 Dose Expected Early 2025 Broad Eligibility Criteria • Unselected CNS patients to accelerate collection of safety and PK data • Received prior therapies • Does not require response- evaluable disease • Late stage patients with no limit on prior recurrences

 
27 ONC206 Appears Well-Tolerated in Adult and Pediatric Patients to Date 1. Adverse Events evaluable for safety. Data extraction from Adult study and Pediatric study as of Dec 2, 2024; preliminary data Related AEs1 Integrated Data Set N=100 All grades Grade ≥ 3 Any Treatment-related AE 49% 2% Fatigue 21% 1% Vomiting 14% 0% Lymphocyte count decreased 9% 0% Headache 8% 0% Nausea 8% 0% White blood cell decrease 7% 0% Neutrophil count decreased 6% 0% Diarrhea 5% 0% ALT increased 5% 1% • Majority of treatment-related adverse events (TRAEs) are mild to moderate in severity • Most frequent TRAEs are fatigue, vomiting and lymphopenia • Occur in a minority of patients • Typical AEs in advanced CNS tumors • No substantial changes in the AE profile as a function of dose or frequency • Similar safety data observed in adults and pediatrics Data cutoff : 02Dec2024

 
28 50mg QW N=10 100mg QW N=11 150mg QW N=12 200mg QW N=18 250mg QW N=14 350 mg QW N=33 50mg BID; TIW N=9 150mg QD; TIW N=14 100mg BID; TIW N=6 150mg BID; TIW N=33 200mg BID; TIW Weekly Dosing Multi-day/ week dosing Weekly Dose 2 50 mg 100 mg 150 mg 200 mg 250 mg 350 mg 300 mg 450 mg 600 mg 900 mg 1200mg Treatment- related AE, all grades 60% 73% 58% 56% 57% 67% 44% 43% 17% 33% Grade 1 60% 45% 50% 39% 50% 67% 33% 36% 17% 33% Grade 2 30% 45% 42% 33% 43% 33% 11% 21% 0% 33% Grade 3 0% 9% 8% 0% 0% 0% 0% 0% 0% 0% Grade 4/5 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% ONC206 Dose Escalation and Intensification Appears Well-Tolerated to Date Majority of treatment related AEs1 are mild to moderate in severity with fatigue most common 1. Adverse Events. Data extraction from Adult study and Pediatric study as of 02Dec2024, preliminary data 2. Weight-based dosing utilized in pediatric patients <60 kg 3. Adults only Incidence of ONC206-Related AEs1 En ro lli ng

 
29 ONC206 Patient Exposures with Intensified Dosing Exceeded Exposures Associated with Nonclinical Efficacy 1. PK summary based on adult data; pediatric PK in DL 1-7 have been similar to adult 2. Average IC50 of 562 nM across 1088 cancer cell lines representing 25 tumor types 3. In vivo models include High-grade glioma (50 mg/kg QW), medulloblastoma (50 mg/kg BID TIW, 100 mg/kg and 120 mg/kg QW, 100 mg/kg BIW), endometrial (125 mg/kg QW, 100 mg/kg BIW), ovarian (125 mg/kg QW), TNBC (100 mg/kg BIW, 50 mg/kg BID TIW), hepatocellular (80 mg/kg BIW), cholangiocarcinoma (50 mg/kg QW) and SCLC (50 mg/kg BID TIW). Average AUC in positive nonclinical models ~5000 ng*hr/mL . 4. Mean AUC tissue:plasma ratio in single oral dose healthy mouse study 5. Adults only • Cmax exceeded IC50 in diverse CNS and non- CNS solid tumor cell lines2 • AUC exceeded plasma exposures in nonclinical solid tumor models demonstrating efficacy3 • Favorable tumor/ tissue: plasma ratios in target organs of nonclinical models4 • adrenals ~7x, uterus ~6x, lung ~6x, prostate ~4x, CNS ~2x • Intensified dosing increased time above IC50 to >24hr while being well-tolerated • Continued dose escalation expected to further enhance duration of exposure to biologically active concentration Relative PK Data from ongoing studies1 Dose Level; Frequency Weekly Dose (mg) Cmax > IC502 Weekly AUC > in vivo model3 Time above IC502 O nc e- W ee kl y D os in g 50 mg; QW 50 0.8x 0.2x 0 hr 150 mg; QW 150 >3x 0.6x 3 hr 200 mg; QW 200 >7x 1.5x 7 hr 350 mg; QW 350 >9x 2.4x 17 hr M ul ti- da y/ W ee k D os in g 50 mg; BID/TIW 300 0.8x 0.9x 0 hr 150mg; QD/TIW 450 >4x 2.0x 19 hr 100mg; BID/TIW 600 >2x 3.4x 28 hr 150 mg; BID/TIW5 900 Pending 200 mg; BID/TIW 1200 Open to enrollment

 
ONC206 Mechanism of Action and Preclinical Efficacy

 
31 • ClpP and DRD2 are direct binding targets that control mitochondrial and pro-survival functions, respectively, in a range of human cancers • ClpP agonism and DRD2 antagonism occurs at nanomolar concentrations • Anti-cancer activity is dependent on ClpP and/or DRD2 depending on tumor type • Downstream effects of engaging ClpP/DRD2 in vitro and in vivo include - altered mitochondrial metabolism - integrated stress response - MYC expression - Akt/ERK signaling - apoptosis ONC206 Is a Second Generation Dual ClpP Agonist/DRD2 Antagonist 1. Maranto et al, AACR Brain Cancer Conference 2023 2. Prabhu et al, AACR 2020 3. Hu et al, Cancers 2020; ClpP catalytic activity is stimulated by ONC2061 ClpP-dependent in vitro activity of ONC206 in T98G high grade glioma cells1 ClpP DRD2-dependent in vitro activity of ONC206 in endometrial cancer ARK2 cells 3 DRD2 signaling is inhibited by ONC206 2 DRD2

 
32 • Nanomolar activity across CNS tumors, including HGG, medulloblastoma and meningioma • In vitro and in vivo data demonstrates enhanced efficacy data with increasing dose and sustained exposure • Tumor regression and survival extension in transgenic and patient-derived medulloblastoma models ONC206 Exhibits Monotherapy Activity in Multiple CNS Cancer Models 1. Jung et al, SNO 2017 2. Maranto et al, AACR Brain Cancer Conference 2023 3. Tzaridis et al, AACR 2024 Transgenic SHH (SmoA1) Medulloblastoma Model3High-grade glioma SF8628 cells2Patient-derived high-grade glioma cultures1 Nanomolar IC50 Efficacy data enhanced with duration Efficacy enhanced with dose (hr)

 
33 • Broadly active across 1088 cancer cell lines representing 25 tumor types with an average IC50 of 562 nM 1 • In vivo results improved with dose intensification in chemo-refractory TNBC, including tumor regressions2 • Improved results relative to dordaviprone in endometrial cancer3 Monotherapy Results & Tolerability of ONC206 in Several Non-CNS Solid Tumors pheochromocytoma, triple-negative breast (TNBC)2, endometrial3, cholangiocarcinoma1, ovarian4, hepatocellular cancer5, small cell lung cancer 1. Prabhu et al, AACR 2020 2. Baek et al, SABCS 2023 3. Hu et al, Cancers 2020 4. Tucker et al, American Journal of Cancer Research, 2022 5. Cao et al, Neoplasia 2024 ARK1 Human Endometrial Cancer Xenograft (ONC201/ONC206 100mg/kg BIW; 6 wks)3 BCM2665 Human TNBC PDX2 Tumor Regressions with Increased Dose Frequency Enhanced in vivo results hPheo cell lines Enhanced in vitro results in PCPG cell lines

 
34 1. Rapidly Emerging Antiviral Drug Development Initiative Ongoing Pipeline Development • ONC212 GPR132 + ClpP agonist - GLP-tox studies complete, potential to advance to IND, work performed with support from academic grants - Preclinical studies are ongoing to evaluate additional oncology indications and predictive biomarkers for ONC212 for clinical development • CMX521 broad spectrum coronavirus preclinical activity - Developed thru Phase 1 in norovirus - Monotherapy efficacy in mouse-adapted SARS-CoV-2- MA10 model across multiple endpoints - $2m grant to fund research collaboration with University of North Carolina/READDI1

 
Corporate Update

 
36 Potential for Imipridones Beyond Brain Tumors Results of Phase II Study of dordaviprone (ONC201) in Neuroendocrine Tumors at the Cleveland Clinic1 5/14 patients treated > 1 year 11/14 patients experienced tumor regression 1. https://aacrjournals.org/clincancerres/article/28/9/1773/694456/Phase-II-Study-of-ONC201-in-Neuroendocrine-Tumors • Single agent responses in Pheochromocytoma and Paraganglioma (PCPG): adrenal-related tumors with high malignant DRD2 expression • Investigator initiated trial at Cleveland Clinic in a heavily refractory and pretreated patient population (n=14) • Superior tolerability and administration profiles relative to SOC therapies

 
37 TEMBEXA is an internally-developed anti-viral program approved by FDA in 2021 and divested to Emergent in an asset sale agreement in 2022. Emergent BioSolutions is an experienced biodefense company collaborating with government agencies to protect public health Terms summary: • $238 million received upfront at closing in Q3 2022 • Up to an additional $124 million in potential BARDA procurement milestones • 20% royalty on future U.S. gross profit with volumes above 1.7 million courses of therapy • 15% royalty of all international gross profit • Up to an additional $12.5 million in development milestones TEMBEXA® Deal Term Summary

 
38 Investment Highlights and Key Catalysts Dordaviprone U.S. NDA submission planned for Dec ‘24, potential U.S. accelerated approval in 2025  No approved therapies currently in recurrent H3 K27M diffuse glioma, an invariably lethal Grade 4 glioma (World Health Org)  Total addressable market exceeds $1Bn in U.S. (U.S. incidence >2,000 patients, ultra-orphan drug pricing)  Patent protection thru 2037 (potential additional U.S. patent term extension)  Front-line Ph 3 trial (ACTION study) substantial enrollment, active in >150 sites and 17 countries  Application for Rare Pediatric Disease Priority Review Voucher (PRV) to be included in upcoming NDA ONC206 Recommended Phase 2 dose expected early 2025  Pharmacokinetic data from dose escalation studies demonstrate dose proportionate exposure  No unexpected safety events and no dose limiting toxicities to date  Exhibits monotherapy activity in multiple non-clinical CNS models as well as tumors outside the CNS $152 million in capital to fund operations as of September 30, 2024 Positioned to accelerate growth from internal and/or external innovation  Robust business development search and evaluation process Planned NDA submission in December 2024 Potential accelerated approval in Q3 2025 Imipridone pipeline progressing

 
Chimerix Corporate Presentation

 
v3.24.3
Cover
Dec. 09, 2024
Cover [Abstract]  
Document Type 8-K
Document Period End Date Dec. 09, 2024
Entity Registrant Name Chimerix, Inc.
Entity Incorporation, State or Country Code DE
Entity File Number 001-35867
Entity Tax Identification Number 33-0903395
Entity Address, Address Line One 2505 Meridian Parkway
Entity Address, Address Line Two Suite 100
Entity Address, City or Town Durham
Entity Address, State or Province NC
Entity Address, Postal Zip Code 27713
City Area Code 919
Local Phone Number 806-1074
Written Communications false
Soliciting Material false
Pre-commencement Tender Offer false
Pre-commencement Issuer Tender Offer false
Title of 12(b) Security Common Stock, par value $0.001 per share
Trading Symbol CMRX
Security Exchange Name NASDAQ
Entity Emerging Growth Company false
Amendment Flag false
Entity Central Index Key 0001117480
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