UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 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): November 2, 2023
(Exact name of registrant as specified in its charter)
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| incorporation) | ||||||||||||||
| (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:
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Securities registered pursuant to Section 12(b) of the Act:
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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 2.02 Results of Operations and Financial Condition.
On November 2, 2023, Chimerix, Inc, (the “Company”) announced our financial results for the nine months ended September 30, 2023 in the press release attached hereto as Exhibit 99.1 and incorporated herein by reference.
Item 7.01 Regulation FD Disclosure.
On November 2, 2023, the Company also 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 99.2 to this Current Report on Form 8-K and is incorporated by reference herein.
The information in Item 2.02, Item 7.01 and the attached Exhibit 99.1 and 99.2 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 Item 2.02, Item 7.01 and the attached Exhibit 99.1 and 99.2 shall not be incorporated by reference into any registration statement or other document pursuant to the Securities Act of 1933, as amended.
| Item 9.01 | Financial Statements and Exhibits. | ||||
(d)Exhibits
| Exhibit No. | Description | |||||||
| 99.1 | ||||||||
| 99.2 | ||||||||
| 104 | Cover 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: November 2, 2023 | |||||||||||
| By: | /s/ Michael T. Andriole | ||||||||||
| Name: | Michael T. Andriole | ||||||||||
| Title: | President and Chief Executive Officer | ||||||||||
Chimerix Reports Third Quarter 2023 Financial Results and Provides Operational Update
– Phase 3 ACTION Study Ongoing with 113 Sites Activated Across 12 Countries; Interim Survival and PFS Data on Track to Report in 2025 –
– Actively Recruiting ONC206 Dose Escalation Studies; Enrollment on Track to Complete First Half 2024 –
– Conference Call at 8:30 a.m. ET Today –
DURHAM, N.C., November 2, 2023 (GLOBE NEWSWIRE) -- Chimerix (NASDAQ:CMRX), a biopharmaceutical company whose mission it is to develop medicines that meaningfully improve and extend the lives of patients facing deadly diseases, today reported financial results for the third quarter ended September 30, 2023 and provided an operational update.
“The third quarter was marked by strong progress across our first-in-class imipridone pipeline, including continued enrollment in our global Phase 3 ACTION study of ONC201 for the treatment of H3 K27M-mutant diffuse glioma,” said Mike Andriole, Chief Executive Officer of Chimerix. “We continue to see strong interest in the ACTION study globally supported by a robust publication strategy, including the recently published front-line treatment and mechanistic data in the peer-reviewed journal Cancer Discovery. These data demonstrated a statistically significant increase in median overall survival (mOS) versus historical controls in a patient population with very few treatment options. As enrollment in the ACTION study continues to progress, we are also working extensively on our second-generation compound, ONC206, to identify biomarkers in patients most likely to respond in future primary efficacy studies. These early data indicate such studies may include both Central Nervous System (CNS) tumors as well as solid tumors outside of the CNS. Finally, we were delighted to join the neuro-oncology community at the European Association of Neuro-Oncology (EANO) Annual Meeting in Rotterdam last month and look forward to the upcoming Society for Neuro-Oncology (SNO) Annual Meeting in Vancouver where multiple oral presentations will highlight a series of preclinical and clinical studies of ONC201 as both monotherapy and as a potential backbone in combinatorial diffuse midline glioma (DMG) treatment settings.”
ONC201 for Treatment of H3 K27M-Mutant Diffuse Glioma
The Phase 3 ACTION trial is currently enrolling patients at 113 sites in 12 countries and remains on track to report first interim overall survival data in early 2025.
The ACTION trial is enrolling patients shortly after front-line radiation therapy. The study is designed to enroll 450 patients randomized 1:1:1 to receive 625mg of ONC201 once per week (the Phase 2 dosing regimen), 625mg twice per week on two consecutive days or placebo. The dose will be scaled by body weight for patients <52.5kg.
In August 2023, a Cancer Discovery publication reported promising survival outcomes for 71 H3 K27M-DMG patients treated with ONC201. In addition, ONC201 reversed a molecular signature of the H3 K27M mutation in patient’s tumor samples.
ONC206
ONC206 is a second generation ClpP agonist and DRD2 antagonist that has demonstrated monotherapy anti-cancer activity in pre-clinical models in primary CNS tumors and solid tumors outside of the CNS. Phase I dose escalation trials continue at the National Institutes of Health (NIH) and the Pacific Pediatric Neuro-Oncology Consortium (PNOC) in adult and pediatric CNS tumor patients, respectively. To date, ONC206 has been generally well tolerated with no dose limiting toxicities. The dose escalation trials have completed the once weekly dosing schedules. The study is currently dosing at more frequent dose schedules that are expected to increase the duration of therapeutic exposure.
Third Quarter 2023 Financial Results
Chimerix reported a net loss of $24.0 million, or $0.27 per basic and diluted share, for the third quarter of 2023. During the same period in 2022, Chimerix recorded net income of $241.4 million, or $2.75 per basic and diluted share.
Research and development expenses increased to $17.4 million for the third quarter of 2023, compared to $15.3 million for the same period in 2022.
General and administrative expenses increased to $9.3 million for the third quarter of 2023, compared to $5.3 million for the same period in 2022. This increase is in connection with the retirement of the CEO and transition to Chairman which resulted in a one-time non-cash expense being recognized related to historical equity grants, the vesting of which remain contingent on future service in the new role.
Chimerix’s balance sheet at September 30, 2023 included $217 million of capital available to fund operations, approximately 88.9 million outstanding shares of common stock and no outstanding debt. Chimerix expects to end the year with over $200 million in cash and cash equivalents, which is expected to be sufficient to fund operations through final ACTION study data expected in 2026.
Conference Call and Webcast
Chimerix will host a conference call and live audio webcast to discuss third quarter 2023 financial results and provide a business update today at 8:30 a.m. ET. To access the live conference call, please dial 646-307-1963 (domestic) or 800-715-9871 (international) at least five minutes prior to the start time and refer to conference ID 5615320. A live audio webcast of the call will also be available on the Investors section of Chimerix’s website, www.chimerix.com. An archived webcast will be available on the Chimerix website approximately two hours after the event.
About Chimerix
Chimerix is a biopharmaceutical company with a mission to develop medicines that meaningfully improve and extend the lives of patients facing deadly diseases. The Company’s most advanced clinical-stage development program, ONC201, is in development for H3 K27M-mutant glioma.
Forward-Looking Statements
This press release 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, enrollment and interest in the Phase 3 ACTION study, the potential future studies of ONC206, the ability to generate or reproduce clinical and pre-clinical findings, and projections regarding timing of enrollment of our clinical studies and future data readouts, and the Company’s cash position and runway. 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.
CONTACTS:
Michelle LaSpaluto
919-972-7115
ir@chimerix.com
Will O’Connor
Stern Investor Relations
212-362-1200
Will@sternir.com
CHIMERIX, INC.
CONSOLIDATED BALANCE SHEETS
(in thousands, except share and per share data)
(unaudited)
| September 30, 2023 | December 31, 2022 | ||||||||||
| ASSETS | |||||||||||
| Current assets: | |||||||||||
| Cash and cash equivalents | $ | 14,118 | $ | 25,842 | |||||||
| Short-term investments, available-for-sale | 180,357 | 191,492 | |||||||||
| Accounts receivable | 11 | 1,040 | |||||||||
| Prepaid expenses and other current assets | 6,136 | 9,764 | |||||||||
| Total current assets | 200,622 | 228,138 | |||||||||
| Long-term investments | 22,514 | 48,626 | |||||||||
| Property and equipment, net of accumulated depreciation | 248 | 227 | |||||||||
| Operating lease right-of-use assets | 1,606 | 1,964 | |||||||||
| Other long-term assets | 292 | 386 | |||||||||
| Total assets | $ | 225,282 | $ | 279,341 | |||||||
| LIABILITIES AND STOCKHOLDERS' EQUITY | |||||||||||
| Current liabilities: | |||||||||||
| Accounts payable | $ | 2,502 | $ | 3,034 | |||||||
| Accrued liabilities | 13,008 | 17,381 | |||||||||
| Total current liabilities | 15,510 | 20,415 | |||||||||
| Line of credit commitment fee | 125 | 250 | |||||||||
| Lease-related obligations | 1,344 | 1,819 | |||||||||
| Total liabilities | 16,979 | 22,484 | |||||||||
| Stockholders’ equity: | |||||||||||
| Preferred stock, $0.001 par value, 10,000,000 shares authorized at September 30, 2023 and December 31, 2022; no shares issued and outstanding as of September 30, 2023 and December 31, 2022 | — | — | |||||||||
| Common stock, $0.001 par value, 200,000,000 shares authorized at September 30, 2023 and December 31, 2022; 88,891,300 and 88,054,127 shares issued and outstanding as of September 30, 2023 and December 31, 2022, respectively | 89 | 88 | |||||||||
| Additional paid-in capital | 986,202 | 970,535 | |||||||||
| Accumulated other comprehensive loss, net | (625) | (337) | |||||||||
| Accumulated deficit | (777,363) | (713,429) | |||||||||
| Total stockholders’ equity | 208,303 | 256,857 | |||||||||
| Total liabilities and stockholders’ equity | $ | 225,282 | $ | 279,341 | |||||||
CHIMERIX, INC.
CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS
(in thousands, except share and per share data)
(unaudited)
| Three Months Ended September 30, | Nine Months Ended September 30, | ||||||||||||||||||||||
| 2023 | 2022 | 2023 | 2022 | ||||||||||||||||||||
| Revenues: | |||||||||||||||||||||||
| Procurement revenue | $ | — | $ | 31,971 | $ | — | $ | 31,971 | |||||||||||||||
| Contract and grant revenue | 11 | 503 | 271 | 503 | |||||||||||||||||||
| Licensing revenue | — | 81 | 49 | 536 | |||||||||||||||||||
| Total revenues | 11 | 32,555 | 320 | 33,010 | |||||||||||||||||||
| Cost of goods sold | — | 333 | — | 447 | |||||||||||||||||||
| Gross profit | 11 | 32,222 | 320 | 32,563 | |||||||||||||||||||
| Operating expenses: | |||||||||||||||||||||||
| Research and development | 17,396 | 15,263 | 53,144 | 52,350 | |||||||||||||||||||
| General and administrative | 9,304 | 5,313 | 19,431 | 16,785 | |||||||||||||||||||
| Total operating expenses | 26,700 | 20,576 | 72,575 | 69,135 | |||||||||||||||||||
| (Loss) income from operations | (26,689) | 11,646 | (72,255) | (36,572) | |||||||||||||||||||
| Other income: | |||||||||||||||||||||||
| Interest income and other, net | 2,703 | 199 | 8,321 | 182 | |||||||||||||||||||
| Gain on sale of business, net | — | 229,670 | — | 229,670 | |||||||||||||||||||
| (Loss) income before income taxes | (23,986) | 241,515 | (63,934) | 193,280 | |||||||||||||||||||
| Income tax expense | — | 153 | — | 153 | |||||||||||||||||||
| Net (loss) income | (23,986) | 241,362 | (63,934) | 193,127 | |||||||||||||||||||
| Other comprehensive (loss) income: | |||||||||||||||||||||||
| Unrealized gain (loss) on debt investments, net | 188 | 31 | (288) | (16) | |||||||||||||||||||
| Comprehensive (loss) income | $ | (23,798) | $ | 241,393 | $ | (64,222) | $ | 193,111 | |||||||||||||||
| Per share information: | |||||||||||||||||||||||
| Net (loss) income, basic | $ | (0.27) | $ | 2.75 | $ | (0.72) | $ | 2.21 | |||||||||||||||
| Net (loss) income, diluted | $ | (0.27) | $ | 2.75 | $ | (0.72) | $ | 2.17 | |||||||||||||||
| Weighted-average shares outstanding, basic | 88,620,666 | 87,634,888 | 88,500,813 | 87,388,624 | |||||||||||||||||||
| Weighted-average shares outstanding, diluted | 88,620,666 | 87,814,330 | 88,500,813 | 89,070,831 | |||||||||||||||||||
Chimerix Corporate Presentation November 2, 2023
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 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.
3 Investment highlights • 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 • 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 • 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 High probability of success for Phase 3 ACTION study of ONC201 Low barriers to commercial potential for ONC201 Corporate capability and financial flexibility
4 Program Preclinical Phase 1 Phase 2 Registrational FDA review Collaborators Deep pipeline across all development stages ONC201 (dordaviprone) H3 K27M-mutant glioma (orphan drug,1 fast track2 and rare pediatric disease designations3) IITs- signal finding, multiple oncology indications/combinations CMX521 SARS-CoV-2 CNS4 tumors ONC206 IND-enabling studies ONC212 TEMBEXA® transacted with Emergent BioSolutions Smallpox (orphan drug designation) APPROVED June 4, 2021 5 National Institutes of Health 1 Malignant glioma 2 Adult recurrent H3 K27M-mutant high-grade glioma 3 H3 K27M-mutant glioma 4. Central Nervous System 5. Rapidly Emerging Antiviral Drug Development Initiative
ONC201 (dordaviprone) Phase 2 Efficacy Analysis
6 • 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 • DMGs harboring the H3 K27M mutation are WHO Grade IV; historically invariably lethal • Consistently longer OS of ONC201-treated H3 K27M DMG patients across: - Diverse external controls (historical, trials) - Sensitivity analysis (early event censoring) - Isolated tumor locations (thalamus, brainstem) H3 K27M-mutant diffuse glioma: high unmet need Natural Disease History4 (n=43) ONC201 Phase 2 (n=50) Median OS, mo (95% CI) 5.1 (3.9-7.7) 13.7 (8-20.3) OS @ 12mo (95% CI) 23.6% (11.7-37.9) 57% (41-70) OS @ 24mo (95% CI) 11.1% (3.3-24.2) 35% (21-49) Histone H3 Mutations in CNS Tumors1 Recurrent H3 K27M DMG3 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 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% Frontline H3 K27M DMG2
7 • 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-LGG criteria 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 Phase 2 efficacy for ONC201 in recurrent H3 K27M DMG
8 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 FDA-aligned criteria for Phase 2 efficacy analysis to isolate ONC201 single agent activity
9 • 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 ONC201 waterfall plot – 30% RANO HGG / LGG response RANO HGG (enhancing) • 20% response • 40% disease control RANO LGG (non-enhancing) • 26% response • 42% disease control ONC201 Ph 2 Efficacy Analysis by BICR in Recurrent H3 K27M-mutant Diffuse Midline Glioma Change > 100%, PR=partial response, MR=minor response, SD=stable disease, NE=not evaluable, PD=progressive disease
10 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 ONC201 Ph 2 Efficacy Analysis by BICR in Recurrent H3 K27M-mutant Diffuse Midline Glioma
11 RANO HGG response correlation to performance status (PS) supports early-line trial Predictably, 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%) Supports hypothesis that treating earlier in disease course may enhance efficacy ONC201 Ph 2 Efficacy Analysis by BICR in Recurrent H3 K27M-mutant Diffuse Midline Glioma
12 Clinically meaningful and durable RANO-HGG responses 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. Duration of response, median (95% CI) 11.2 months (3.8 – not reached) Time to response, median (range) 8.3 months (1.9 – 15.9) ONC201 Phase 2 Efficacy Analysis by BICR in Recurrent H3 K27M-mutant Diffuse Midline Glioma
13 Treatment-related Adverse Events, Integrated Safety Data Set, (N=211 glioma patients) 2 Related TEAEs All grades Grade > 3 Any Treatment-related AE 55.5% 11.8% Fatigue 21.8% 2.8% Nausea 20.4% 0 Vomiting 14.2% 0.5% Headache 8.5% 0.5% Lymphocyte count decreased 6.6% 0.5% Decreased appetite 5.7% 0 White blood cell count decreased 4.7% 0.5% ALT increased 4.3% 0.5% Hypophosphataemia 4.3% 0 Neutrophil count decreased 3.8% 0.5% Anaemia 3.3% 0 Diarrhea 3.3% 0 ONC201 safety 1. Based on available data as 25Apr2023 for ONC201-101 2. Reported in ONC201 Investigator Brochure Healthy Adult Dose Escalation Study1 Incidence of ONC201-Related Adverse Events (AE) Treatment-related Adverse Events in > 3% Glioma Patients • In addition to healthy adult dose escalation study above, clinical pharmacology studies included: food-effect, safety pharmacology, special populations, and drug-drug interaction studies • Treatment-related AEs were generally Grade 1 and transient across the clinical pharmacology program. • The most commonly reported treatment-related events were mild dizziness, headache and nausea. 125 mg N=33 375 mg N=15 625 mg N=45 Any treatment-related AE 36.0% 20.0% 53.0% Grade 1 36.0% 20.0% 53.0% Grade 2 0 0 0 Grade 3-5 0 0 0
14 All patients RANO HGG Responders RANO HGG and/or LGG Responders N 50 10 15 PFS at 12 months (number of patients censored) 30%1 90% (0) 67% (2) OS at 24 months (number of patients censored)2 35%1 80% (2) 53% (5) Corticosteroids response3 (number of patients evaluable) 47% (15) 100% (4) 100% (5) Performance status response4 (number of patients evaluable) 21% (34) 60% (5) 67% (9) RANO responses correspond with survival & clinical benefit 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 converted into a dexamethasone equivalent dose. Baseline ≥4mg 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 timepoint. Baseline KPS/LPS ≤80 were evaluable. ONC201 Ph 2 Efficacy Analysis by BICR in Recurrent H3 K27M-mutant DMG • No patients who experienced a RANO- HGG response had a reported death at 24 months2 • RANO response strongly associated with reduction in steroid use and improvement in performance status
15 Experimental Agent Ph2 Design Biomarker Response criteria Confounded by anti-angiogenic pseudo response ORR Duration of response 6 month PFS Approved? ONC201– Ph2 rDMG Single agent H3 K27M RANO BICR No 20-30% 11.2 35% To be determined Temozolomide Single agent - Levin No 5% ? 21% Yes (OS) Bevacizumab Various - Various Yes 20-70% 4-6 18-50% Yes (AA per ORR, PFS) Cediranib Single agent - MacDonald Yes 27% ? 26% No Rindopepimut Combo + Avastin EGFRv3 RANO Yes 30% 7.8 28% No Depatuxizumab mafodotin Single agent - RANO No 7% 6.7 29% No Enzastaurin Combo + Avastin - RANO Yes 22% ? 21% No Strong rationale for phase 3 success relative to recent GBM trials Positive Neutral Negative Characteristics WKA Yung, et al, British Journal Cancer, Aug 8, 2000; Teri Kreisl, et all, Journal Clinical Onocoloy,2009, Feb 10;27(5);740-5; Tracy Batchelor, et. all, Journal of Clinical Oncology, vol28, issue 17, Jun 10, 2010; David Reardon, et al, Clin Cancer Research Apr 2020; 26(7)1586-1594; Martin van den Bent, et al, Cancer Chemo & Pharma, 26 Oct 2017 80, 1209-1217; Yazmin Odia, et al, Journal Neuro-Oncology 127, 127-125 (2016)
ONC201 Phase 3 ACTION Study Summary
17 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 ONC201 twice weekly (625mg ONC201 day 1 + day 2) ONC201 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
18 Multiple unique aspects to ONC201 data support translation to phase 3 success Isolated, durable single agent activity Consistency across multiple endpoints Enhanced activity not required, but likely • Responses not confounded by combination treatments • Responses were gradual, durable, and multi-focal • Responses observed via most stringent criteria in blinded assessment • Earlier setting associated with higher response rate (performance status, tumor volume) • Addition of higher-dose study arm • Biomarker selection supports patient homogeneity • Responses highly associated with other forms of clinical benefit • PFS and OS favorable to historical benchmarks • Multiple separate analyses suggest longer survival of patients who received ONC201
19 Design provides multiple paths for success Interim data expected in early 2025 and final data in 2026 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 ONC201 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
20 Potential to increase ONC201 efficacy with dose schedule • Once per week ONC201 dosing effective as monotherapy in Phase 2 studies • Twice per week dosing on two consecutive days expected to increase duration of therapeutic exposure - Increased exposure time can increase glioma sensitivity to ONC201 in vitro - Generally well tolerated in Phase 1 without dose limiting toxicity or AEs leading to dose modification • Phase 3 ACTION study will evaluate once per week and twice per week dosing schedules at 625mg (or body weight equivalent) 24 hours48+ hours Incubation Time
ONC201 Market Opportunity Assessment
22 (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.) • ~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; ~5,000 patients in the top seven global markets 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
23 • No approved therapies for H3 K27M mutant glioma, ONC201 is the leading program targeting this mutation globally • Potential market opportunity ~$750 million • Approximately 5,000 patients in top seven markets • Ultra-orphan indication drug pricing • H3 K27M mutations most often in children / young adults (little exposure to Medicare) • Low barriers to adoption - No effective alternative therapies - High unaided awareness among neuro-oncologists - Mutation routinely identified by existing diagnostics - Longer-term, potentially combinable with other glioma therapies • Patent protection for lead indication into 2037 - potential U.S. patent term extension (up to five years) H3 K27M-mutant glioma: rapid ramp to peak revenue expected
24 Regulatory designations 1. Subject to continuation of Rare Pediatric Disease Voucher Program and proceeds from voucher will be split 50/50 with legacy Oncoceutics shareholders US - Orphan Drug Designation (ODD) (treatment of glioblastoma and treatment of malignant glioma) EU - ODD for treatment of glioma Fast Track Designation (FTD) for adult recurrent H3 K27M-mutant high-grade glioma Rare Pediatric Disease Designation for treatment of H3 K27M mutant glioma - Potential to receive rare pediatric voucher1
25 • Single agent responses in Ph 2 neuroendocrine trial of ONC201 observed in subset (paraganglioma) • Paraganglioma are adrenal-related tumors with elevated DRD2 expression • Five patients have been treated > 1 year • Fewer short-term and potential long-term toxicities than other paraganglioma therapies ONC201 interim efficacy results in dopamine-secreting tumors outside the brain 1. ASCO oral presentation June 2021 -75 -50 -25 0 25 50 75 B es t c ha ng e in tu m or b ur de n fr om ba se lin e (% ) 50% ORR in paraganglioma PD Ph 2 Study of ONC201 in Neuroendocrine Tumors in investigator-reported data from ongoing clinical trial NCT # (NT03034200)
ONC201 Mechanism of Action
27 • ONC201 can selectively induce apoptosis in cancer cells by altering the activity of two protein targets • DRD2 antagonism - DRD2 is a G protein-coupled neuroreceptor that regulates Ras signaling - ONC201 antagonizes DRD2, inhibiting Ras signaling pathways • ClpP agonism - ClpP normally degrades misfolded proteins in mitochondria - ONC201 modifies ClpP conformation, promoting excess degradation of specific mitochondrial proteins important for cancer cell viability ONC201 directly engages DRD2 and ClpP ONC201 upregulates integrated stress response, inactivates Akt/ERK, and selectively induces tumor cell death 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;
28 Cancer Discovery publishes front-line ONC201 survival data and elucidates H3 K27M mechanism of action Mitochondrial effects reverse H3 K27me3-loss hallmark of H3 K27M H3 K27me3-loss reversal evident in ONC201- treated H3 K27M patients Front-line ONC201 following RT survival benefit Increased confidence in Ph3 dose Provides ClpP connection to H3 K27M Anchors MOA directly to targeting H3 K27M Extends documented benefit to front-line, pediatrics, and brainstem
ONC206
30 ONC206: oral brain penetrant DRD2 antagonist + ClpP agonist 1. PDB 6CM4 2. PDB 6DL7 DRD21 ClpP2 ONC206• Second generation imipridone designed to expand to new indications • Efficacy in cell culture, xenograft and transgenic central nervous system (CNS) and other tumor models • Oral dose escalation trials ongoing in CNS cancers • Monotherapy response reported by investigator in early dose escalation cohort for a patient in recurrent non-H3 K27M GBM - Dordaviprone responses amongst CNS tumors exclusively in H3K27M gliomas - Dose level 2 (100mg), once weekly dosing
31 CNS Tumors Glioblastoma1 Medulloblastoma2 ONC206 monotherapy active in models of CNS and other cancers 1. Theeler et al, SNO 2020 2. Malhotra et al, ISPNO, 2020 3. Hu et al, Cancers 2020 4. Tucker et al, American Journal of Cancer Research, 2022 Weeks P<0.05 ARK1 Human Endometrial Cancer Xenograft (100mg/kg BW; 6 wks)3 Non-CNS Solid Tumors Endometrial cancer3 Ovarian cancer4 Cholangiocarcinoma1 Transgenic Medulloblastoma Model2 Su rv iv al Control ONC206 (100mg/kg QW) ONC206 (120mg/kg QW)
32 ONC206 dose escalation: pediatric and adult CNS tumors • Monotherapy dose escalation trials enrolling in parallel for adult and pediatric CNS tumors • Response reported by investigator from early cohort (100mg QW) without H3 K27M mutation - 18-year-old patient with recurrent temporal lobe glioblastoma - Regression on MRI & metabolic reduction via PET imaging, continuing on therapy over 15 months • Once weekly dose escalation is expected to intensify to three consecutive days per week National Institutes of Health
33 • Consecutive day dosing may increase therapeutic response - In vitro data demonstrates enhanced efficacy with 72 hour sustained exposure - Toxicology data enables safe escalation to more prolonged exposures • Phase 1 trial data suggest a therapeutic and safe exposure possible with twice daily, three times weekly dosing Dose intensification expected to enhance duration of therapeutic exposure 1. Internal modeling 72 hours Incubation Time C el l V ia bi lit y (% ) Pr ed ic te d pl as m a O N C 20 6 (n g/ m L) Time (hours) HGG in vitro response to ONC206 enhanced with exposure time PK model from ongoing adult Phase 1 trial1
34 ONC206 dose escalation to more frequent dosing ongoing 1. Dose level 6 was conducted in adults only 2. Pediatric dose scaled by body weight • No DLTs observed with weekly dosing • Similar safety profile in adults and pediatrics • Majority of treatment-related AEs are mild to moderate • Most common treatment- related events are fatigue, lymphocyte count decreased, and vomiting • No dose related toxicity with dose escalation – dose escalation continuing 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 level2 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 50 m g 10 0 m g 15 0 m g 20 0 m g 30 0 m g 35 0 m g Once weekly dosing 3 consecutive days dosing 1 Dose escalation on track for completion in 1H24 In vitro data indicates correlation between exposure time and tumor cell viability; more frequent dosing schedule designed to increase duration of target exposure
35 • GBM is a rapidly progressive disease with low survival rates, few drug approvals last 25 years: - Temozolomide (TMZ) approved 1999 - Bevacizumab approved 2009 • Existing therapies rarely offer durable effect - 3-year survival from diagnosis • Chimerix retains global operational rights to ONC2062 • Worldwide market opportunity exceeds $2Bn - TMZ revenue peaked at approximately $1.4 billion in 2009, prior to going generic o Inflation adjusted peak: > $2.5Bn - New GBM therapy: 50% penetration at average price of contemporary oncology drug approvals exceeds $2Bn ~30,000 new cases of GBM annually in the top 7 markets; >$2Bn market opportunity 1 wjso.biomedcentral.com/articles/10.1186/1477-7819-10-220 2 Royalties and milestones are owed to legacy Oncoceutics shareholders by virtue of the 2021 merger agreement 1 out of 201
Preclinical Development ONC212 and CMX521
37 • Distinct molecular target (GPR132) and efficacy profile relative to ONC201/ONC206 • Efficacy in preclinical models of advanced cancers • GLP-tox studies complete, potential to advance to IND • Partnerships established for early-stage clinical trials with Brown University and MD Anderson Cancer Center • Preclinical studies are ongoing to evaluate additional oncology indications and predictive biomarkers for ONC212 for clinical development ONC212: GPR132 + ClpP Agonist 1. Lev et al, Oncotarget 2017 Pancreatic cancer model shows the potential of ONC2121 Vehicle ONC201 ONC212
38 • Ribonucleoside analog that is a viral polymerase inhibitor - Inhaled nebulized liquid aerosol formulation; minimal systemic exposure • Monotherapy efficacy in mouse-adapted SARS-CoV-2-MA10 model across multiple endpoints - Lung viral titer - Viral RNA parallel viral lung titer (plaque forming unit) - Clinical scoring (animal health) - Lung pathology - Animal weight loss CMX-521: anti-SARS-CoV-2 preclinical activity Not significant Viral Lung Titer Replicating SARS-COV-2-MA101 Treatment initiation Hours post-infection (HPI)$2 million grant to fund prodrug formulations that could enable oral administration with improved lung delivery 1. Replicates lung pathology of human infection 4-days post-infection. One day in mouse is 5-7 days in humans (adjusted disease course).
Corporate Update
40 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
41 Financial strength supports development through key catalysts Fully funded Ph 3 program with multiple potential paths to approval First-Line H3 K27M-mutant diffuse glioma – The ACTION Study Trial initiated November 2022 Interim OS data expected early 2025, full OS data expected 2026 ONC206 in early dose escalation studies at NIH and PNOC Investigator reported response in Non-H3 K27M recurrent glioblastoma patient $217 million in capital to fund operations as of September 30, 2023, no debt Early-stage pipeline leverages external capital Pre-clinical programs potential to advance to clinic or partner (ONC212, CMX521) Robust business development search and evaluation process High probability of success for Phase 3 ACTION study of ONC201 Low barriers to commercial potential for ONC201 Corporate capability and financial flexibility
Chimerix Corporate Presentation