Fatty acid oxidation disorder

The STRIDE study did not meet its primary or secondary efficacy endpoint The company to suspend mavodelpar development and implement a workforce reduction Reneo Pharmaceuticals, Inc. (NASDAQ: RPHM), a pharmaceutical company focused on the development and commercialization of therapies for patients with rare genetic mitochondrial diseases, today announced its pivotal STRIDE study (NCT04535609) of mavodelpar in adult patients with primary mitochondrial myopathies (PMM) did not meet its primary efficacy or secondary efficacy endpoint. The primary efficacy endpoint of the trial was the change from baseline in the distance walked during the 12-minute walk test (12MWT) at week 24. The secondary efficacy endpoint was the change from baseline in the PROMIS® Short Form Fatigue 13a score. “We are immensely thankful to all the patients, families, and healthcare professionals who participated in the mavodelpar PMM development program,” said Gregory J. Flesher, President and CEO of Reneo Pharmaceuticals. “Although the results of the STRIDE study were negative, the data generated are vitally important to the scientific community and we will make these data available once the final analyses are complete. Finally, I want to thank all Reneo employees for their dedication and tireless contributions to advancing the science of mitochondrial disease.” The company intends to implement immediate cost savings initiatives, including suspension of the ongoing STRIDE AHEAD study and all other mavodelpar development activities and a workforce reduction of approximately 70%. The company currently has over $100 million in cash, cash equivalents, and short-term investments. The STRIDE study was a global, randomized, double-blind, placebo-controlled pivotal Phase 2b trial of mavodelpar in adult patients with PMM due to mitochondrial DNA (mtDNA) defects. The study was designed to investigate the efficacy and safety of 100 mg mavodelpar administered once-daily over a 24-week period. The primary efficacy endpoint of the trial was the change from baseline in the distance walked during the 12-minute walk test (12MWT) at week 24. Secondary and exploratory endpoints included changes from baseline in PROMIS® Short Form Fatigue 13a, Modified Fatigue Impact Scale (MFIS), Patient Global Impression of Change (PGIC), Patient Global Impression of Severity (PGIS), 30 Second Sit-To-Stand (30STS) Test, Brief Pain Inventory (BPI), 36-Item Health Survey (SF-36), Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP), and Pedometer Step Count. The STRIDE AHEAD study was an open-label extension (OLE) trial being conducted outside of the United States in adult patients with PMM due to mtDNA defects who participated in the STRIDE study, the mavodelpar Phase 1b study, and mavodelpar-naïve patients with PMM due to nuclear DNA (nDNA) defects. The study was designed to evaluate the long-term safety and tolerability of 100 mg mavodelpar administered once-daily over a 24-month period. PMM are a group of rare, genetic metabolic disorders caused by mutations or deletions in the mtDNA or nDNA. These genetic alterations hamper the ability of mitochondria to generate energy from nutrient sources, resulting in energy deficits that are most pronounced in tissues with high energy demand such as muscle, brain, and heart. The symptoms of PMM include muscle weakness, exercise intolerance, movement disorder, deafness, blindness, and droopy eyelids among others. The prognosis for these disorders ranges in severity from progressive weakness to death. Mavodelpar (REN001) is a potent and selective peroxisome proliferator-activated receptor delta (PPARδ) agonist which has been studied in two rare genetic mitochondrial diseases that typically present with myopathy and have high unmet medical needs: PMM and long-chain fatty acid oxidation disorder. For additional information, please see clinicaltrials.gov. Reneo is a pharmaceutical company focused on the development and commercialization of therapies for patients with rare genetic mitochondrial diseases, which are often associated with the inability of mitochondria to produce adenosine triphosphate (ATP). For additional information, please see reneopharma.com. The content above comes from the network. if any infringement, please contact us to modify.

Reneo's rare genetic disease treatment aspirations are circling the drain. Reneo Pharmaceuticals’ rare genetic disease study has missed both primary and secondary goals, prompting the California biotech to halt the development of its only asset and lay off 70% of staff. The news, shared Thursday morning, sent the company’s stock plummeting 87%, down from $7.75 per share at market close yesterday to 98 cents as of 10:15 a.m. ET today. The data drop comes from a phase 2b trial—dubbed STRIDE—that assessed the peroxisome proliferator-activated receptor delta (PPARδ) agonist mavodelpar among adults with primary mitochondrial myopathies, a group of genetic metabolic disorders with severity ranging from progressive weakness to death. The study was designed to evaluate the efficacy and safety of once-daily 100 mg doses of mavodelpar over 24 weeks. The global, double-blind study failed to hit its primary efficacy endpoint—the change from baseline in distance walked during a 12-minute walk test at week 24—or secondary efficacy endpoint of the change from baseline in fatigue. Given the results, Reneo is implementing an immediate cost-savings plan that includes a 70% workforce reduction. The layoffs are expected to be completed by Dec. 31, according to Securities and Exchange Commission filings.  The biotech is also suspending development of all other mavodelpar development activities, including an open-label extension trial designed to evaluate the safety and tolerability of daily 100 mg mavodelpar doses over two years. The company was also testing out mavodelpar—the only asset listed in its pipeline—in another form of rare, genetic metabolic disorders called long-chain fatty acid oxidation disorders.   Reneo said it currently has more than $100 million in cash, equivalents and short-term investments on hand.

Topline data results from the pivotal STRIDE study are expected in December 2023IRVINE, Calif., Nov. 13, 2023 (GLOBE NEWSWIRE) -- Reneo Pharmaceuticals, Inc. (Nasdaq: RPHM), a clinical-stage pharmaceutical company focused on the development and commercialization of therapies for patients with rare genetic mitochondrial diseases, today reported financial results for the third quarter ended September 30, 2023 and provided a business update. “We are looking forward to sharing topline results of our pivotal STRIDE study in December,” said Gregory J. Flesher, President and CEO of Reneo Pharmaceuticals. “In addition, we continue to be encouraged by the high participation rate in our STRIDE AHEAD open-label extension study, and are happy to announce enrollment of our first patient with PMM due to nuclear DNA defect in this ongoing trial. This is a very exciting time for the Reneo team and we want to thank our clinicians, patients, and stakeholders for supporting the mavodelpar development program.” Third Quarter and Recent Highlights Completed last patient last visit in the pivotal STRIDE study in adult patients with primary mitochondrial myopathies (PMM) due to mitochondrial DNA (mtDNA) defects; topline results expected in December 2023Enrolled 88% of eligible STRIDE study patients in the STRIDE AHEAD open-label extension study; 65 patients treated beyond 52-weeksDosed the first patient with PMM due to a nuclear DNA (nDNA) defect in the STRIDE AHEAD open-label extension studyPresented multiple posters at scientific conferences highlighting additional mavodelpar dataReceived Notice of Allowance from the U.S. Patent and Trademark Office for patent application No. 18/101,527 entitled “Use of PPAR-Delta Agonists in the Treatment of Disease,” with anticipated expiration in 2041Repurchased 576,443 shares of our common stock for an aggregate purchase price of approximately $4.4 million directly from vTv Therapeutics, LLC in a private, non-underwritten transaction on October 30, 2023; all repurchased shares were retired Financial Results for the Three Months Ended September 30, 2023 We reported a net loss of $19.2 million, or $0.57 per share, during the third quarter of 2023, compared to a net loss of $13.0 million, or $0.53 per share, for the same period in 2022. We had $125.6 million in cash, cash equivalents, and short-term investments as of September 30, 2023. Research and development (R&D) expenses were $13.6 million during the third quarter of 2023, compared to $9.9 million for the same period in 2022. This increase in R&D expenses was primarily due to an increase of $2.2 million related to clinical development and contract manufacturing costs to support the marketing registration for mavodelpar, an increase of $1.0 million in medical affairs costs, and an increase of $0.9 million in personnel-related costs due to additional headcount, offset by a decrease of $0.5 million of other R&D activities. General and administrative (G&A) expenses were $7.3 million during the third quarter of 2023, compared to $3.9 million for the same period in 2022. This increase in G&A expenses was primarily due to an increase of $2.1 million in commercial development activities and an increase of $1.2 million in facility and personnel-related costs due to additional headcount. About STRIDE The STRIDE study is a global, randomized, double-blind, placebo-controlled pivotal Phase 2b trial of mavodelpar in adult patients with PMM due to mtDNA defects. The study is designed to investigate the efficacy and safety of 100 mg mavodelpar administered once-daily over a 24-week period. The primary efficacy endpoint of the trial is the change from baseline in the distance walked during the 12-minute walk test (12MWT) at week 24. Secondary and exploratory endpoints include changes from baseline in PROMIS® Short Form Fatigue 13a, Modified Fatigue Impact Scale (MFIS), Patient Global Impression of Change (PGIC), Patient Global Impression of Severity (PGIS), 30 Second Sit-To-Stand (30STS) Test, Brief Pain Inventory (BPI), 36-Item Health Survey (SF-36), Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP), and Pedometer Step Count. About STRIDE AHEAD The STRIDE AHEAD study is an open-label extension (OLE) trial being conducted outside of the United States in patients with PMM due to mtDNA defects who participated in the STRIDE study or the mavodelpar Phase 1b study. The study is designed to evaluate the long-term safety and tolerability of 100 mg mavodelpar administered once-daily over a 24-month period. STRIDE AHEAD was amended to allow enrollment of treatment naïve patients with PMM due to nDNA defects. About PMM PMM are a group of rare, genetic metabolic disorders caused by mutations or deletions in the mtDNA or nDNA. These genetic alterations hamper the ability of mitochondria to generate energy from nutrient sources, resulting in energy deficits that are most pronounced in tissues with high energy demand such as muscle, brain, and heart. The symptoms of PMM include muscle weakness, exercise intolerance, movement disorder, deafness, blindness, and droopy eyelids among others. The prognosis for these disorders ranges in severity from progressive weakness to death. About Mavodelpar Mavodelpar (REN001) is a potent and selective peroxisome proliferator-activated receptor delta (PPARδ) agonist currently in clinical development for two rare genetic mitochondrial diseases that typically present with myopathy and have high unmet medical needs: PMM and long-chain fatty acid oxidation disorder. For additional information, please see clinicaltrials.gov. About Reneo Pharmaceuticals Reneo is a clinical-stage pharmaceutical company focused on the development and commercialization of therapies for patients with rare genetic mitochondrial diseases, which are often associated with the inability of mitochondria to produce adenosine triphosphate (ATP). Our lead product candidate, mavodelpar (REN001), is a potent and selective agonist of the peroxisome proliferator-activated receptor delta (PPARδ). Mavodelpar has been shown to increase transcription of genes involved in mitochondrial function, increase fatty acid oxidation, and may increase production of new mitochondria. For additional information, please see reneopharma.com. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the potential development, registration and commercialization of mavodelpar, the timing of topline results from the STRIDE study and the anticipated expiration for patent applications. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “plans,” “will,” “believes,” “anticipates,” “expects,” “intends,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Reneo’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Reneo’s business in general, and the other risks described in Reneo’s filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Reneo undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. RENEO PHARMACEUTICALS, INC.Consolidated Balance Sheets(In thousands, except share and par value data) September 30,2023 December 31,2022 (Unaudited) Assets Current assets: Cash and cash equivalents $11,737 $19,927 Short-term investments 113,877 81,246 Prepaid expenses and other current assets 3,158 5,180 Total current assets 128,772 106,353 Property and equipment, net 529 453 Right-of-use assets 1,006 1,292 Other non-current assets 81 84 Total assets $130,388 $108,182 Liabilities and stockholders’ equity Current liabilities: Accounts payable $2,473 $1,893 Accrued expenses 10,765 4,827 Operating lease liabilities, current portion 325 404 Total current liabilities 13,563 7,124 Operating lease liabilities, less current portion 812 1,059 Performance award 1,069 29 Total liabilities 15,444 8,212 Commitments and contingencies Stockholders’ equity: Common stock, $0.0001 par value; 200,000,000 shares authorized at September 30, 2023 and December 31, 2022; 33,872,166 and 24,699,553 shares issued and outstanding at September 30, 2023 and December 31, 2022, respectively 3 3 Additional paid-in capital 305,479 236,693 Accumulated deficit (190,517) (136,683)Accumulated other comprehensive loss (21) (43)Total stockholders’ equity 114,944 99,970 Total liabilities and stockholders’ equity $130,388 $108,182 RENEO PHARMACEUTICALS, 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 Operating expenses: Research and development $13,622 $9,938 $39,009 $27,348 General and administrative 7,266 3,902 19,038 11,938 Total operating expenses 20,888 13,840 58,047 39,286 Loss from operations (20,888) (13,840) (58,047) (39,286)Other income 1,692 833 4,213 931 Net loss (19,196) (13,007) (53,834) (38,355)Unrealized gain (loss) on short-term investments 10 (194) 22 (60)Comprehensive loss $(19,186) $(13,201) $(53,812) $(38,415)Net loss per share attributable to common stockholders, basic and diluted $(0.57) $(0.53) $(1.81) $(1.57)Weighted-average shares used in computing net loss per share, basic and diluted 33,807,945 24,496,313 29,718,689 24,472,974 RENEO PHARMACEUTICALS, INC.Consolidated Statements of Cash Flows(In thousands)(Unaudited) Nine Months EndedSeptember 30, 2023 2022 Cash flows from operating activities Net loss $(53,834) $(38,355)Adjustments to reconcile net loss to net cash used in operating activities: Stock-based compensation 3,793 3,103 Depreciation and amortization 126 63 Amortization/accretion on short-term investments (3,551) (169)Changes in the fair value of performance award 1,040 (378)Non-cash lease expense 354 338 Loss on disposal of fixed asset 5 3 Changes in operating assets and liabilities: Prepaid expenses and other assets 2,025 1,146 Accounts payable and accrued expenses 6,507 2,838 Operating lease liabilities (394) (338)Net cash used in operating activities (43,929) (31,749)Cash flows from investing activities Purchases of property and equipment (196) (96)Purchase of available-for-sale short-term investments (190,058) (67,329)Proceeds from maturities of available-for-sale short-term investments 161,000 36,500 Net cash used in by investing activities (29,254) (30,925)Cash flows from financing activities Proceeds from public offering of common stock, net of offering costs 58,862 — Proceeds from private placement of common stock, net of offering costs 4,667 — Proceeds from issuance of common stock under the at-the-market facility, net of offering costs 1,009 — Proceeds from issuance of common stock in connection with equity plans 455 146 Net cash provided by financing activities 64,993 146 Net decrease in cash and cash equivalents (8,190) (62,528)Cash and cash equivalents, beginning of period 19,927 124,660 Cash and cash equivalents, end of period $11,737 $62,132 Noncash operating activities: Right-of-use assets obtained in exchange for lease obligations $— $1,524 Noncash investing and financing activities: Property and equipment in accounts payable $11 $— Contacts: Danielle Spangler Investor Relations Reneo Pharmaceuticals, Inc. dspangler@reneopharma.com Matthew Purcell Media Inquiries Russo Partners, LLC matthew.purcell@russopartnersllc.com