Dordaviprone

Nov. 11, 2024 -- 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 announced upcoming presentations at the 2024 Society for Neuro-Oncology (SNO) Annual Meeting, which will be held in Houston, TX from November 21 – 24, 2024. “We are excited to provide an updated assessment of objective response to dordaviprone previously reported in the blinded independent central review (BICR) cohort1 in recurrent H3 K27M-mutant diffuse midline glioma using Response Assessment in Neuro-Oncology (RANO) 2.02, the most recently established criteria for this disease. This analysis demonstrates an overall response rate of 28.0%, a median time to response of 4.6 months plus a median duration of response of 10.4 months,” said Allen Melemed, MD, Chief Medical Officer at Chimerix. We expect to include the updated RANO 2.0 results in our planned upcoming New Drug Application to Australian regulators.” “RANO 2.0 is a recently established response assessment criteria for gliomas that supersedes prior versions such as RANO-HGG and RANO-LGG. RANO 2.0 incorporates an integrated quantitative assessment of both enhancing and non-enhancing disease that were not adequately assessed by prior criteria. In addition, it includes minor responses, which in certain regions of the brain, such as midline structures, have disproportionate clinical benefit. This benefit often includes meaningful improvement in neurological symptoms and quality of life outcomes,” said Patrick Y. Wen, MD, Director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute. Details for the RANO 2.0 presentation as well as other pipeline presentations at SNO are as follows: Title: Response by RANO 2.0 criteria in ONC201 (dordaviprone)-treated patients with recurrent H3 K27M-mutant diffuse midline glioma Abstract Code: CTNI-54 Session Date and Time: Friday, November 22, 2024, from 7:30-9:30 PM Location: The George R. Brown Convention Center, Hall B3 Title: Allosteric mitochondrial ClpP agonist ONC206 alters stress response, metabolic and epigenetic profiles to elicit anti-cancer efficacy in high-grade gliomas Abstract Code: EXTH-37 Session Date and Time: Friday, November 22, 2024, from 7:30-9:30 PM Location: The George R. Brown Convention Center, Hall B3 Title: Safety of ONC201 treatment in patients with previously treated H3 K27M-mutant glioma: results from ONC028, an ongoing compassionate use program Abstract Code: NCOG-07 Abstract Session: CNS Rare Tumors Presentation Date and Time: Saturday, November 23, 2024, from 10:45am-12:15pm Title: Early reduction in MRI diffusion apparent diffusion coefficient (ADC) strongly predicts long term response to ONC201 therapy in patient with H3K27M-DMG Abstract Code: NIMG-29 Abstract Session: Pediatrics II Presentation Date and Time: Saturday, November 23, 2024, from 10:45am-12:15pm 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. Arrillaga-Romany, et al, Journal of Clinical Oncology, Feb 2024 Wen, et al, Journal of Clinical Oncology, Sept 2023 The content above comes from the network. if any infringement, please contact us to modify.

– Phase 3 ACTION Study On-Track with First Interim Overall Survival Data Expected Third Quarter 2025 – – IDMC Recommends Continuing Conduct of ACTION Study As-Is Following Preplanned Safety Review – – Alignment with TGA to Submit Dordaviprone for Provisional Approval in Australia – – Conference Call at 8:30 a.m. ET Today – DURHAM, N.C., Nov. 07, 2024 (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, 2024 and provided an operational update. “We have sustained execution of the Phase 3 ACTION study and continue to be encouraged by the safety profile of dordaviprone following the Independent Data Monitoring Committee’s (IDMC) preplanned safety review which recommended continuing study conduct as-is, including at the more intense twice per week dose. Additionally, the Therapeutic Goods Administration (TGA) has granted orphan drug designation to dordaviprone, and we have alignment to file a New Drug Application (NDA) for Provisional Approval in Australia which we expect to occur in the coming months,” said Mike Andriole, Chief Executive Officer of Chimerix. “As we complete the dordaviprone NDA and look toward the balance of the year, we also expect to complete enrollment in a Phase 1 dose escalation study of ONC206 as we consider future development scenarios for this program.” “In addition, we were delighted to announce the promotion of Dr. Josh Allen to the role of Chief Scientific Officer this quarter. Josh has been instrumental in the discovery and development of the imipridone class of compounds and expect his broad expertise in cancer biology and strong business acumen will underpin Chimerix early phase development for years to come,” added Mr. Andriole. Dordaviprone (ONC201) Dordaviprone, a first-in-class imipridone, has the potential to be the first treatment approved for H3 K27M-mutant diffuse glioma. It is an oral small molecule that crosses the blood-brain barrier and selectively binds to the mitochondrial protease ClpP and the dopamine receptor D2 (DRD2). Dordaviprone's unique mechanism of action includes alterations of key epigenetic modifications such as reversal of H3 K27me3-loss which is the hallmark of H3 K27M-mutant gliomas. Dordaviprone is being evaluated in the Phase 3 ACTION trial that is currently enrolling H3 K27M-mutant diffuse glioma patients at over 145 sites in 15 countries. Chimerix expects interim OS data in the third quarter of 2025. For more information on the ACTION trial, please visit www.clinicaltrials.gov Earlier this year, Chimerix initiated the evaluation process for dordaviprone to be considered for Provisional Registration in Australia. The Provisional Registration process is a three-step process which begins with a Pre-Submission Meeting evaluating current data, as well as other program features, including the status of pivotal studies. The second step, the Provisional Determination Application, was approved during the third quarter 2024, as was the application for Orphan Drug Designation in Australia. The final step is the NDA submission for Provisional Registration which is expected to occur in the coming months with potential commercial availability as soon as year-end 2025. ONC206 The imipridone ONC206 is a second generation ClpP agonist and DRD2 antagonist which also crosses the blood-brain barrier and is 10x more potent in vitro than dordaviprone. It has demonstrated monotherapy anti-cancer activity in vivo in central nervous system (CNS) tumor models, as well as in vivo solid tumors models outside of the CNS. The two Phase 1 dose escalation trials conducted in partnership with the Pacific Pediatric Neuro-Oncology Consortium (PNOC) and the National Institutes of Health (NIH) have enrolled over 80 pediatric and adult patients with unselected CNS tumors, with no dose limiting toxicity observed to date. The safety profile of ONC206 has been consistent across both pediatric and adult populations, with the majority of treatment-related adverse events being mild to moderate, including fatigue, lymphocyte count decrease and vomiting. No significant change in the overall safety profile has been reported to date as dosing has escalated and intensified in frequency from once per week to twice per day on three consecutive days per week. Completion of enrollment in the remaining dose escalation cohorts is expected to occur in 2024. Assessment of objective responses in patients where a monotherapy treatment effect can be reliably evaluated is ongoing in dose cohorts at or above target exposure thresholds. The company expects to assess any objective responses in the first half of 2025, allowing sufficient time for response onset and confirmation in current and future dose cohorts. Additionally, ONC206 nonclinical studies remain ongoing to identify candidate oncology indications and biomarkers to inform future development plans. Corporate In September 2024, Chimerix promoted Joshua E. Allen, PhD, to the role of Chief Scientific Officer after previously serving as Chief Technology Officer. Dr. Allen co-discovered the anti-cancer activity of ONC201 and co-invented the imipridone class of compounds. He has continuously advanced the research and development of dordaviprone from academic discovery to its registration program, along with the creation and clinical introduction of biologically distinct derivatives. He received his Ph.D. in Biochemistry and Molecular Biophysics from the University of Pennsylvania. Several research publications, patents, grants, and awards reflect his scientific and entrepreneurial efforts in oncology, including recognition on the Forbes 30 under 30 list. Prior to joining Chimerix, Dr. Allen served as Chief Scientific Officer at Oncoceutics. Third Quarter 2024 Financial Results Chimerix reported a net loss of $22.9 million, or $0.26 per basic and diluted share, for the third quarter of 2024. During the same period in 2023, Chimerix recorded a net loss of $24.0 million, or $0.27 per basic and diluted share. Research and development expenses increased to $19.6 million for the third quarter of 2024 compared to $17.4 million for the same period in 2023. General and administrative expenses decreased to $5.2 million for the third quarter of 2024 compared to $9.3 million for the same period in 2023. This decrease is due to a one-time non-cash expense related to historical equity grants recognized during the 2023 period. Chimerix’s balance sheet at September 30, 2024 included $152.4 million of capital available to fund operations, approximately 89.9 million outstanding shares of common stock and no outstanding debt. Conference Call and Webcast Chimerix will host a conference call and live audio webcast to discuss third quarter 2024 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 6580777. 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, dordaviprone (ONC201), is in development for H3 K27M-mutant diffuse glioma. The Company is conducting Phase 1 dose escalation studies of ONC206 to evaluate safety and PK data. 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, expectations regarding interim OS data from the ACTION study, plans for Provisional Registration and commercialization in Australia, expectations regarding completion of enrollment and assessment of responses in the ONC206 dose escalation trials, and the characteristics and development of ONC206. 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; 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 our clinical candidates; 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. CONTACT: Will O’ConnorStern Investor Relations212-362-1200will@sternir.com CHIMERIX, INC. CONSOLIDATED BALANCE SHEETS (in thousands, except share and per share data) (unaudited) September 30, December 31, 2024 2023 ASSETS Current assets: Cash and cash equivalents $23,645 $27,661 Short-term investments, available-for-sale 112,585 155,174 Accounts receivable 155 4 Prepaid expenses and other current assets 4,517 6,271 Total current assets 140,902 189,110 Long-term investments 16,201 21,657 Property and equipment, net of accumulated depreciation 281 224 Operating lease right-of-use assets 1,089 1,482 Other long-term assets 195 301 Total assets $158,668 $212,774 LIABILITIES AND STOCKHOLDERS' EQUITY Current liabilities: Accounts payable $5,340 $2,851 Accrued liabilities 16,904 15,592 Total current liabilities 22,244 18,443 Line of credit commitment fee - 125 Lease-related obligations 644 1,177 Total liabilities 22,888 19,745 Stockholders’ equity: Preferred stock, $0.001 par value, 10,000,000 shares authorized at September 30, 2024 and December 31, 2023; no shares issued and outstanding as of September 30, 2024 and December 31, 2023; no shares issued and outstanding as of September 30, 2024 and - - Common stock, $0.001 par value, 200,000,000 shares authorized at September 30, 2024 and December 31, 2023; 89,936,053 and 88,929,300 shares issued and outstanding as of September 30, 2024 and December 31, 2023, respectively 90 89 Additional paid-in capital 996,389 988,457 Accumulated other comprehensive gain, net 258 7 Accumulated deficit (860,957) (795,524) Total stockholders’ equity 135,780 193,029 Total liabilities and stockholders’ equity $158,668 $212,774 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, 2024 2023 2024 2023 Revenues: Contract and grant revenue $26 $11 $155 $271 Licensing revenue - - - 49 Total revenues 26 11 155 320 Operating expenses: Research and development 19,646 17,396 56,918 53,144 General and administrative 5,173 9,304 15,252 19,431 Total operating expenses 24,819 26,700 72,170 72,575 Loss from operations (24,793) (26,689) (72,015) (72,255)Other income: Interest income and other, net 1,914 2,703 6,582 8,321 Net loss (22,879) (23,986) (65,433) (63,934)Other comprehensive loss: Unrealized gain (loss) on debt investments, net 466 188 251 (288)Comprehensive loss $(22,413) $(23,798) $(65,182) $(64,222)Per share information: Net loss, basic and diluted $(0.26) $(0.27) $(0.73) $(0.72)Weighted-average shares outstanding, basic and diluted 89,701,117 88,620,666 89,531,017 88,500,813