8-K
OnKure Therapeutics, Inc. (OKUR)
8-K
2021-08-11
For: 2021-08-11
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April 06, 2026
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):
August 11, 2021
Reneo Pharmaceuticals, Inc.
(Exact name of registrant as specified in its charter)
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|---|---|---|---|---|
| Delaware | 001-40315 | 47-2309515 | ||
| (State or other jurisdiction<br><br>of incorporation) | (Commission<br><br>File Number) | (I.R.S. Employer<br><br>Identification No.) |
| <br><br> | |
|---|---|
| 18575 Jamboree Road , Suite 275-S ,<br>Irvine , California **** | 92612 |
| (Address of principal executive offices) | (Zip Code) |
Registrant’s telephone number, including area code: ( 858 ) 283-0280
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 class | Trading Symbol(s) | Name of each exchange on which registered |
| Common stock, par value $0.0001 per share | RPHM | The Nasdaq Stock Market LLC |
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 7.01Regulation FD Disclosure.
On August 11, 2021, Reneo Pharmaceuticals, Inc. (the “Company”) updated its corporate slide presentation for use in meetings with investors, analysts and others. The presentation is available through the Company’s website and a copy is attached as Exhibit 99.1 to this Current Report on Form 8-K.
The information in this Item 7.01 of this Current Report on 8-K (including Exhibit 99.1) is furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended. The information shall not be deemed incorporated by reference into any other filing with the Securities and Exchange Commission made by the Company, whether made before or after today’s date, regardless of any general incorporation language in such filing, except as shall be expressly set forth by specific references in such filing.
Item 9.01Financial Statements and Exhibits.
(d) Exhibits.
| 99 | | |
|---|---|---|
| Exhibit No. | Description | |
| 99.1 | | Corporate Slide Presentation, dated August 11, 2021. |
| 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.
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| | Reneo Pharmaceuticals, Inc. | ||
| | | ||
| Date: August 11, 2021 | By: | | /s/ Gregory J. Flesher |
| | | | Gregory J. Flesher |
| | | | Chief Executive Officer |
Exhibit 99.1
| Nasdaq: RPHM<br>August 2021<br>Focused on Improving the Lives of Patients with Rare Genetic Mitochondrial Diseases |
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| 2<br>Forward-Looking Statements<br>This presentation may not be reproduced, retransmitted or further distributed to any other person or published, in whole or in part, for any other purpose. This<br>presentation regarding Reneo Pharmaceuticals, Inc.(the “Company”) is for you to familiarize yourself with the Company. This presentation is for information and education<br>purposes only. No reliance may be placed for any purpose whatsoever on the information contained in this document or on assumptions made as to its completeness. This<br>presentation contains forward-looking statements that are based on the beliefs and assumptions of the Company’s management team, and on information currently<br>available to such management team. These forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond the Company’s control.<br>All statements, other than statements of historical fact, contained in this presentation, including statements regarding future events, future financial performance, business<br>strategy and plans, and objectives of the Company for future operations, are forward-looking statements. Although the Company does not make forward-looking<br>statements unless it believes it has a reasonable basis for doing so, the Company cannot guarantee their accuracy. These statements are only predictions and involve<br>known and unknown risks, uncertainties and other factors, which may cause the actual results, levels of activity, performance or achievements of the Company and the<br>Company’s industry to be materially different from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking<br>statements. You should not place undue reliance on any forward-looking statement. The Company undertakes no obligation to update or revise publicly any of the forward-<br>looking statements after the date hereof to conform the statements to actual results or changed expectations except as required by law.<br>This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our<br>industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections,<br>assumptions, and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of<br>uncertainty and risk. These and other factors could cause results to differ materially from those expressed in the estimates made by the independent parties and by us.<br>This presentation discusses a product candidate that is under clinical study and which has not yet been approved for marketing by the U.S. Food and Drug Administration.<br>No representation is made as to the safety or effectiveness of this product candidate for the use for which it is being studied. |
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| 3<br>Investment Highlights<br>Secure Cash<br>Position<br>Significant<br>Unmet Need<br>Clinical<br>Milestones<br>Novel Product<br>Candidate<br>• Preliminary efficacy<br>and tolerability<br>observed in clinical<br>trials<br>• Favorable guidance<br>from U.S. and<br>European regulatory<br>agencies<br>• Myopathy with<br>limitations in physical<br>activity and reduced<br>life expectancy<br>• No approved<br>treatment options<br>for most patients<br>• Ongoing clinical<br>trials in three rare<br>mitochondrial<br>diseases<br>• Data from clinical<br>trials anticipated<br>in 2022 and 2023<br>• $167 million in cash,<br>cash equivalents, and<br>short-term<br>investments as of<br>June 30, 2021<br>• Anticipated runway<br>through the end of<br>2023<br>Rx |
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| REN001 Overview<br>11 4 |
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| 5<br>REN001 Addresses Many Forms of Mitochondrial Disease<br>Preclinical Phase 1 Phase 2 Phase 3 Anticipated Milestones<br>PMM Data from PMM global Phase 2b trial (2023)<br>Data from PMM open-label safety trial (2023) primary mitochondrial<br>myopathies<br>LC-FAOD Data from LC-FAOD Phase 1b trial (1H 2022)<br>Data from LC-FAOD natural history study (2H 2022) long-chain fatty acid<br>oxidation disorders<br>McArdle Data from McArdle Phase 1b trial (1Q 2022) glycogen storage<br>disease type V<br>Reneo is initially developing REN001 for patients with three rare genetic mitochondrial<br>diseases that typically present with myopathy and have high unmet medical needs |
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| 6<br>Significant Opportunity in Key Pharmaceutical Markets<br>Patients in Europe<br>(Northern/Western)<br>• United Nations World Population Prospects 2019, Rev.166200<br>• Gorman G et al. Ann Neurol. 2015; 77(5): 753–759 (PMM)<br>•Merritt JL et al. Ann Transl Med. 2018; 6(24): 473 (LC-FAOD)<br>• De Castro M et al. Genet Med. 2015; 17(12): 1002–1006 (McArdle)<br>Patients in China<br>Patients in Japan<br>Commercialization by Reneo<br>Commercialization by partners<br>Patients in U.S.<br>PMM: 66,200<br>LC-FAOD: 5,000<br>McArdle: 6,600<br>PMM: 82,500<br>LC-FAOD: 6,200<br>McArdle: 8,300<br>PMM: 287,900<br>LC-FAOD: 21,600<br>McArdle: 28,800<br>PMM: 25,300<br>LC-FAOD: 1,900<br>McArdle: 2,500<br>Patients in Brazil<br>PMM: 42,500<br>LC-FAOD: 3,200<br>McArdle: 4,300 |
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| 7<br>REN001: Selective PPARδ Agonist<br>Sources:<br><br><br><br><br><br>1. Increases transcription<br>of genes central to<br>mitochondrial function<br>2. Drives production of<br>new mitochondria<br>3. Increases oxidation of<br>fatty acids and cellular<br>energy production<br>PPARδ EC50 = 31nM<br>PPARa EC50 > 10μM<br>PPARγ EC50 > 10μM<br>PPAR Delta (δ)<br>• Member of PPAR<br>family that<br>regulates cellular<br>energy generation<br>• Present in multiple<br>tissues including<br>muscle, kidney,<br>brain, and liver<br>• Activation in muscle<br>stimulated by<br>increased cellular<br>need for energy |
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| 8<br>Leg Immobilization Study Overview<br>Randomized, placebo-controlled clinical trial in healthy adult subjects to assess muscle strength<br>Primary Objective:<br>Evaluate safety and tolerability of 28 days of REN001 in healthy volunteers<br>Secondary Objectives:<br>Characterize changes in muscle strength, muscle size, and expression of PPARδ regulated genes known to<br>be involved in mitochondrial function and mitochondrial biogenesis<br>29 1 14 Day<br>REN001 100 mg BID (N=12)<br>BL<br>49<br>Placebo (N=12)<br>Follow-up<br>Leg immobilized for the first 14 days |
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| 9<br>REN001 Treatment Increased Muscle Strength vs. Placebo<br>-36.2<br>2.7<br>-5.9<br>32.8<br>-40<br>-25<br>-10<br>5<br>20<br>35<br>1 hour after removal of leg<br>brace (p<0.01)<br>1 week after removal of leg<br>brace (p<0.004)<br>Muscle Strength (Pounds)<br>Placebo REN001<br>(p-value from a mixed model with baseline value as covariate )<br>Mean change from baseline in muscle strength<br>• No serious adverse events (SAEs)<br>related to REN001<br>• Treatment emergent adverse events<br>(TEAEs) were similar among subjects<br>who received REN001 or placebo<br>• REN001 treated subjects had<br>substantially more leg strength than<br>placebo-treated subjects<br>• Greater preservation of muscle<br>strength following immobilization<br>• Greater increase in muscle strength<br>one week after removal of the leg<br>brace |
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| 10<br>0.0<br>1.0<br>2.0<br>3.0<br>4.0<br>Baseline Day 14 Day 16 Day 21 Day 29<br>Normalized Change (Log2 Values)<br>PDK4 ANGPTL4 SLC25A34<br>Increases in PPARδ-regulated Gene Expression Observed<br>• REN001 treated subjects showed<br>increases in expression of several PPARδ-<br>regulated genes<br>• Pyruvate dehydrogenase lipoamide kinase<br>isozyme 4 (PDK4) encodes for a protein that<br>plays a key role in regulation of glucose and<br>fatty acid metabolism<br>• Angiopoietin-like 4 (ANGPTL4) encodes for a<br>protein that is directly involved in regulating<br>lipid metabolism<br>• Solute carrier family 25 member 34<br>(SLC25A34) encodes for a protein that is<br>known to transport molecules across the<br>mitochondrial membrane<br>Expression of PPARδ-regulated genes<br>from muscle biopsies |
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| Primary Mitochondrial Myopathies (PMM)<br>Characteristics<br>• PMMs are rare disorders caused by mutations within mitochondrial DNA (mtDNA) or nuclear DNA<br>(nDNA)<br>• Mutations hamper the ability of mitochondria to generate energy<br>• Alterations most pronounced in tissues with high energy demand (muscle, brain, and heart)<br>Symptoms<br>• Debilitating fatigue<br>• Myopathy<br>• Exercise intolerance<br>• Muscle pain<br>• Severe lack of endurance<br>Prevalence<br>• Approximately 20:100,000*<br>Current Treatments<br>• No approved therapies<br>• Over-the-counter vitamins<br>and supplements commonly<br>used<br>*Gorman G et al. Ann Neurol. 2015; 77(5): 753–759 (PMM) 11 |
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| 12<br>PMM Phase 1b Clinical Trial<br>Open-label clinical trial in adult subjects with genetically confirmed mtDNA mutations and myopathy<br>Primary Objective:<br>Evaluate safety and tolerability of 12 weeks of treatment with REN001 in patients with PMM<br>Secondary Objectives:<br>Evaluate safety and tolerability of 48 weeks of REN001 and explore changes in clinical outcome such as<br>exercise tests, oxygen consumption, and symptoms after 12 weeks of treatment with REN001<br>4 12 1 2 8 Week 36-week extension (optional)<br>REN001 100 mg QD REN001 100 mg QD BL |
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| 13<br>500<br>600<br>700<br>800<br>Baseline Week 12<br>Meters<br>• Following 12 weeks of 100 mg once-daily dosing with REN001, patients achieved an average<br>increase of 104 meters in walk distance compared to baseline<br>• 15 of 17 (88%) had an increase in distance walked, with 13 of 17 (76%) increasing ≥60 meters<br>PMM Phase 1b Results – Increases in 12MWT<br>-100 0 100 200 300<br>Distance (meters)<br>12MWT Change from Baseline by Subject (n=17) Mean Change in 12MWT (n=17)<br>+104 meters |
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| 14<br>Time-Based Improvements in Walk Distance Over Baseline<br>• Gains observed in distance walked were associated with improvements in gait mechanics<br>• Greatest increase over baseline occurred after the 6th minute, when fatty acid metabolism is<br>expected to increase<br>phosphocreatine<br>carbohydrate metabolism<br>fatty acid metabolism<br>+6% +5% +26% +22%<br>0<br>50<br>100<br>150<br>200<br>250<br>Minute 1-3 Minute 4-6 Minute 7-9 Minute 10-12<br>Meters<br>Baseline Week 12<br>Mean Change in 12MWT by Period (n=12) |
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| 15<br>Mean Improvements in Peak VO2 Observed Over Baseline<br>• Mean improvement in VO2 of 1.7 mL/kg/min observed at week 12 compared to baseline<br>• No change in heart rate or perceived exertion<br>Peak O2 Consumption (VO2) Change from Baseline<br>by Subject (n=17)<br>Mean Change in Peak Oxygen<br>Consumption (VO2) (n=17)<br>+1.7 mL/kg/min<br>-4 -2 0 2 4 6 8 10 12 14 16<br>VO2 (mL/kg/min)<br>10<br>12<br>14<br>16<br>18<br>20<br>Baseline Week 12<br>mL/kg/min |
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| 16<br>Patient-Reported Outcomes<br>Patients treated with REN001 for 12 weeks reported fewer symptoms compared to baseline<br>• Reduction in pain (mean BPI score from 4.5 at baseline to 3.5)<br>• Reduction in fatigue (mean MFIS score from 50 at baseline to 40)<br>• Improvement in the SF-36 energy/fatigue score (mean score from 28 at baseline to 39)<br>Mean Change in Brief Pain<br>Inventory (n=14)<br>Mean Change in Modified<br>Fatigue Impact Scale (n=17)<br>Mean Change in SF-36<br>Energy/Fatigue (n=17)<br>0<br>1<br>2<br>3<br>4<br>5<br>6<br>7<br>Baseline Week 12<br>Score (Range 0<br>-<br>10)<br>-1.0 point<br>0<br>10<br>20<br>30<br>40<br>50<br>60<br>70<br>Baseline Week 12<br>Score (Range 0<br>-<br>84)<br>-10 points<br>0<br>10<br>20<br>30<br>40<br>50<br>60<br>Baseline Week 12<br>Score (Range 0<br>-<br>100)<br>+11 points<br> = less pain = less fatigue = more energy/less fatigue |
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| 17<br>Summary of Leg Immobilization and Phase 1b Trials<br>• On average, patients experienced an increase of 104m in the 12MWT<br>• On average, patients experienced increases in VO2 max<br>• Changes in in VO2 max were consistent with the observed increases in 12MWT<br>• Substantial reductions in patient-reported pain and fatigue<br>• No treatment-related serious adverse events reported<br>Leg Immobilization Study<br>Phase 1b in Patients with PMM<br>• Observed increases in the expression of PPARd-driven genes compared to placebo<br>• Statistically significant, placebo-corrected improvements in strength compared to placebo<br>• No treatment-related serious adverse events reported |
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| 18<br>STRIDE: Global Phase 2b Clinical Trial in PMM<br>RDBPC clinical trial in patients with PMM caused by mutations in mtDNA<br>52-week open label extension<br>(ex-U.S.)<br>Primary Objective:<br>Change from baseline to week 24 in distance walked during 12MWT<br>Secondary Objectives:<br>Changes from baseline to week 24 in MFIS physical sub-scale and PGIC score<br>Other Assessments:<br>30 second sit to stand test, step count, PGIS score, SF-36, MFIS total, cognitive and psychosocial sub-<br>scale, BPI severity and pain interference, and WPAI:SHP<br>24 2 18 Week<br>REN001 100 mg QD (N=100)<br>BL<br>Placebo (N=100)<br>REN001 100 mg QD<br>REN001 100 mg QD<br>4<br>Enrollment in STRIDE began in July 2021 and topline data is expected in 2023 |
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| Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD)<br>Characteristics<br>• LC-FAOD are inherited genetic errors of metabolism resulting in the inability to use dietary long-chain<br>fatty acids as energy sources<br>• Mutations in genes that code for enzymes that perform long-chain fatty acid oxidation<br>Symptoms<br>• Young children– lethargy,<br>liver dysfunction,<br>hypoglycemia, high risk for<br>sudden death,<br>cardiomyopathy<br>• Older patients – limited<br>endurance, muscle aches,<br>rhabdomyolysis<br>Prevalence<br>• Estimated 1.5:100,000*<br>Current Treatments<br>• DOLJOVI®, a fatty acid<br>supplement similar to<br>medium chain triglyceride oil<br>(MCT)<br>• Therapy includes a fat-<br>restricted diet,<br>supplementing with short or<br>medium chain fatty acids<br>*Merritt JL et al. Ann Transl Med. 2018; 6(24): 473 (LC-FAOD) 19 |
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| 20<br>LC-FAOD Phase 1b Clinical Trial<br>Description<br>Open-label clinical trial in adult subjects with LC-FAOD and CPT2, VLCAD, LCHAD, or TFP mutations<br>Primary Objective:<br>Evaluate safety and tolerability of 12 weeks of REN001 in subjects with LC-FAOD<br>Secondary Objectives:<br>Exploration of changes in clinical outcomes such as 12MWT<br>Changes in symptoms including SF-36 scale, PGI-S, CGI-S, MFIS, BPI, FAOD-MSI, PGI-C<br>BL REN001 50 mg QD or 100 mg QD (n=24)<br>1 12 Week 2 4 8 |
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| 21<br>Improved 12MWT, Reduced Symptoms Observed<br>• Preliminary Results After 12 weeks of treatment with REN001<br>• 5 of 6 subjects (83%) showed an improvement in the 12MWT<br>• 4 of 6 subjects (67%) showing an improvement of 50 meters or greater<br>• Reduction in symptoms, including fatigue (MFIS) and pain (BPI)<br>• Improvements in SF-36 physical functioning and energy/fatigue domains<br>Mean Change from Baseline to Week 12<br>Patient 12MWT (meters) MFIS BPI SF-36 Physical<br>Functioning<br>SF-36 Energy/<br>Fatigue<br>1 -82 -5 0 10 5<br>2 3 16 0.75 -15 -15<br>3 58 2 0 5 -5<br>4 61 -9 -0.5 10 20<br>5 74 -10 -1.5 5 40<br>6 120 -8 -0.75 10 25 |
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| McArdle Disease<br>Characteristics<br>• Rare genetic disorder belonging to a class known as glycogen storage diseases (GSD)<br>• Mutation in gene that encodes for myophosphorylase, a muscle-specific enzyme that breaks down<br>glycogen stored in the muscles<br>• Patients have a debilitating lapse in energy production after a short period of physical exertion<br>Symptoms<br>• Acute muscle pain, severe<br>fatigue, elevated heart rate<br>• Can result in severe<br>rhabdomyolysis, leading to<br>hospitalization/acute kidney<br>failure<br>Prevalence<br>• Approximately 2:100,000*<br>Current Treatments<br>• None<br>*De Castro M et al. Genet Med. 2015; 17(12): 1002–1006 (McArdle) 22 |
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| 23<br>McArdle Disease Phase 1b Clinical Trial<br>REN001 100 mg QD BL<br>Description<br>• Open-label clinical trial in adult subjects with McArdle Disease<br>Primary Objective:<br>• Evaluate safety and tolerability of 12-weeks of REN001 in subjects with McArdle disease<br>Secondary Objectives:<br>• Exploration of changes in clinical outcomes such 12MSWT<br>• Changes in symptoms including SF-36 scale, PGIS-S, PGIS-I, PGIS-C, MFIS, and WPAI<br>1 12 Week 2 4 8 |
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| Patents and Exclusivity |
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| 25<br>Patents & Exclusivity<br>REN001 patent portfolio<br>• 6 U.S. and 19 foreign issued patents covering composition of matter of REN001<br>(expiry in 2026)<br>• 3 U.S. and 5 foreign issued patents, plus 1 U.S. and 2 foreign pending applications covering methods of<br>use (expires 2034)<br>• Pending patent applications covering methods of use, methods of manufacturing, and crystalline<br>forms (polymorphs) (expires 2040-2042, if issued)<br>Anticipated market exclusivity<br>• 7 years for new orphan drug in the U.S. (10 years in Europe and Japan)<br>• 6 months additional exclusivity for pediatric populations |
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| Clinical Milestones |
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| 27<br>REN001 Clinical Development Roadmap<br>2023 2022 2021<br>PMM<br>Open-label<br>enrollment<br>begins<br>(1H 2022)<br>PMM<br>Phase 2b<br>topline<br>results<br>(2023)<br>PMM<br>Phase 2b<br>first patient<br>dosed<br>July 2021<br>PMM<br>Open-label<br>topline<br>results<br>(2023)<br>McArdle<br>Phase 1b<br>topline<br>results<br>(1Q 2022)<br>LC-FAOD<br>Phase 1b<br>topline<br>results<br>(1H 2022)<br>LC-FAOD<br>Natural history<br>topline<br>results<br>(2H 2022) |
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| To learn more, please contact:<br>Vinny Jindal<br>Chief Financial Officer<br>vjindal@reneopharma.com |
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