Flecainide Acetate

- Duchenne: Dosing completed for first three patients in INSPIRE DUCHENNE clinical trial; SGT-003 has been well tolerated in all patients with no SAEs observed; initial three patient data expected Q1 2025 - - Duchenne: Activities undertaken to accelerate development of SGT-003, including: expansion of study protocol in September 2024, activation of additional clinical sites in Q4 2024, additional manufacturing supply to support expanded trial enrollment - - CPVT: SGT-501 IND submission for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT) on track for 1H 2025 - - Cash: Company ends Q3 2024 with approximately $171.1 million in cash, cash equivalents, and available-for-sale securities; Solid has anticipated cash runway into 2026 - CHARLESTOWN, Mass., Nov. 06, 2024 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. (Nasdaq: SLDB) (the “Company” or “Solid”), a life sciences company developing precision genetic medicines for neuromuscular and cardiac diseases, today reported financial results for the third quarter ended September 30, 2024, and provided a business update. “We are highly encouraged by the progress we have made with the INSPIRE DUCHENNE clinical trial over the past quarter, including the activation of University of California, Davis as a clinical site in October,” said Bo Cumbo, President and CEO, Solid Biosciences. “SGT-003 continues to be well tolerated in the first three patients dosed. As a result of encouraging early results observed in these patients, we have implemented an updated study protocol amending the clinical trial across key parameters, including enrollment size, age range, and clinical endpoint timelines. With these changes, along with other planned studies, we believe our clinical development program provides significant flexibility in pursuing potential regulatory pathways, with the goal of accelerating a new treatment option to this underserved patient community. We are currently enrolling patients under the expanded INSPIRE DUCHENNE protocol and will continue dosing throughout the rest of 2024 and into 2025.” Mr. Cumbo continued: “We are committed to presenting clinical data in a thoughtful way that will benefit the Duchenne field and community at large, and we will present safety, expression and biomarker data from the first three patients, along with a trial update, in the first quarter of 2025 following the completion and collective assessment of 90-day muscle biopsies.” “Turning to our cardiac pipeline, we are pleased to share that our IND-enabling, GLP toxicology and proof-of-concept studies for CPVT are progressing as expected, with an anticipated IND submission for SGT-501 in the first half of 2025,” said Gabriel Brooks, M.D., Chief Medical Officer, Solid Biosciences. “Based upon our positive pre-IND meeting with the U.S. Food and Drug Administration (FDA), we are confident that we have a path to rapidly advance this program to the clinic. CPVT is an underdiagnosed and highly malignant, genetic arrhythmia syndrome with historic mortality rates reaching as high as 50% by age 35.1 The treatment landscape has not meaningfully changed in decades, despite the fact that currently available therapies such as beta-blockers and flecainide require a high degree of compliance to be effective, do not treat the underlying cause of the disease, and have multiple unfortunate side effects, including depression, fatigue, weight gain, and impotence. Paradigm-shifting treatments are long overdue for patients and their families, and we believe that our gene therapy has the potential to transform patient care for this disorder for years to come. We look forward to submitting our IND and advancing this program into the clinic, which we believe will mark significant progress toward establishing Solid as a leading cardiac precision genetic medicines company.” Additional Company Highlights AAV-SLB101, Solid’s proprietary capsid used in SGT-003, continues to be well tolerated in the first three patients dosed in the INSPIRE DUCHENNE study, and was well tolerated in NHP and mouse studies. 13 different academic labs and one corporation have begun utilizing AAV-SLB101.Solid continues to advance preclinical studies for TNNT2, BAG3, and other pipeline programs. Third Quarter 2024 Financial Highlights Cash Position: Solid had approximately $171.1 million in cash, cash equivalents, and available-for-sale securities as of September 30, 2024, compared to approximately $123.6 million as of December 31, 2023. The Company expects that its cash, cash equivalents, and available-for-sale securities as of September 30, 2024, will enable it to fund its operational runway into 2026, which includes: investment for the expansion of the INSPIRE DUCHENNE clinical trial, additional manufacturing supply and Phase 3 start up activities (pending results from INSPIRE DUCHENNE), as well as ongoing activities related to other pipeline medicines.Research and Development (R&D) Expenses: R&D expenses for the three months ended September 30, 2024, were $27.3 million, compared to $16.7 million for the three months ended September 30, 2023. The increase of $10.6 million was due to a $5.8 million increase in development program expenses and other research costs, a $3.1 million increase in costs for SGT-501 primarily related to manufacturing and research costs, a $1.1 million increase in external expenses, and a $0.6 million increase in costs for SGT-003 primarily related to clinical and manufacturing costs.General and Administrative (G&A) Expenses: G&A expenses for the three months ended September 30, 2024, were $7.9 million, compared to $6.4 million for the three months ended September 30, 2023. The increase of $1.4 million was primarily related to a $1.5 million increase in personnel related costs, and a $0.2 million increase in consulting fees, offset by a $0.3 million decrease in temporary services.Net Loss: Net loss for the three months ended September 30, 2024, was $32.7 million compared to a net loss of $21.0 million for the same period in 2023. Basic and diluted net loss per share was $0.79 and $1.05 for the three-month periods ended September 30, 2024, and September 30, 2023, respectively. References1. Abbas M, et al. Catecholaminergic Polymorphic Ventricular Tachycardia. Arrhythm Electrophysiol Rev. 2022; 11:e20. About Solid BiosciencesSolid Biosciences is a precision genetic medicine company focused on advancing a portfolio of gene therapy candidates including SGT-003 for the treatment of Duchenne muscular dystrophy (Duchenne), SGT-501 for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), AVB-401 for the treatment of BAG3-mediated dilated cardiomyopathy, and additional assets for the treatment of fatal cardiac diseases. Solid is advancing its diverse pipeline across rare neuromuscular and cardiac diseases, bringing together experts in science, technology, disease management, and care. Patient-focused and founded by those directly impacted, Solid’s mandate is to improve the daily lives of patients living with these devastating diseases. For more information, please visit www.solidbio.com. Forward-Looking StatementsThis press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding future expectations, plans and prospects for the company; the ability to successfully achieve and execute on the company’s goals, priorities and achieve key clinical milestones; the company’s SGT-003 program, including expectations for additional CTA filings, site activations, expanded clinical development, accelerated production of multiple GMP batches of SGT-003, initiation and enrollment in clinical trials, dosing, availability of clinical trial data and potential accelerated approval; the company’s expectations for submission of an IND for SGT-501 and to submit additional INDs by the end of 2026; the cash runway of the company and the sufficiency of the Company’s cash, cash equivalents, and available-for-sale securities to fund its operations; and other statements containing the words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would,” “working” and similar expressions. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with the company’s ability to advance SGT-003, SGT-501, AVB-401 and other preclinical programs and capsid libraries on the timelines expected or at all; obtain and maintain necessary approvals from the FDA and other regulatory authorities; replicate in clinical trials positive results found in preclinical studies and early-stage clinical trials of the company’s product candidates; obtain, maintain or protect intellectual property rights related to its product candidates; compete successfully with other companies that are seeking to develop Duchenne and other neuromuscular and cardiac treatments and gene therapies; manage expenses; and raise the substantial additional capital needed, on the timeline necessary, to continue development of SGT-003, SGT-501, AVB-401 and other candidates, achieve its other business objectives and continue as a going concern. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the company’s actual results to differ from those contained in the forward-looking statements, see the “Risk Factors” section, as well as discussions of potential risks, uncertainties and other important factors, in the company’s most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the company’s views as of the date hereof and should not be relied upon as representing the company’s views as of any date subsequent to the date hereof. The company anticipates that subsequent events and developments will cause the company's views to change. However, while the company may elect to update these forward-looking statements at some point in the future, the company specifically disclaims any obligation to do so. Solid Biosciences Investor Contact:Nicole AndersonDirector, Investor Relations and Corporate CommunicationsSolid Biosciences Inc.investors@solidbio.com Media Contact:Glenn SilverFINN Partnersglenn.silver@finnpartners.com (tables follow) SELECTED FINANCIAL INFORMATION (UNAUDITED) CONDENSED CONSOLIDATED BALANCE SHEETSSeptember 30, December 31,(in thousands, except share data)2024 2023Cash and cash equivalents$64,394 $74,015Available-for-sale securities 106,723 49,625Prepaid expenses and other current assets 8,377 6,094Operating lease, right-of-use assets 24,859 26,539Property and equipment, net 5,067 6,624Other non-current assets 475 209Restricted cash 1,931 1,833Total Assets$211,826 $164,939Accounts payable$3,458 $2,032Accrued expenses and other current liabilities 13,227 10,161Operating lease liabilities 1,718 1,855Finance lease liabilities 1,051 469Derivative liabilities 3,400 —Operating lease liabilities, excluding current portion 21,643 22,707Finance lease liabilities, excluding current portion 307 1,234Total stockholders’ equity 167,022 126,481Total Liabilities and Stockholders’ Equity$211,826 $164,939 Common stock outstanding 38,930 20,387 CONDENSED CONSOLIDATED STATEMENT OF OPERATIONS Three Months EndedSeptember 30, Nine Months EndedSeptember 30, (in thousands, except per share data) 2024 2023 2024 2023 Operating expenses: Research and development $27,327 $16,702 $65,661 $61,110 General and administrative 7,855 6,412 24,171 20,940 Restructuring charges — — — (63)Total operating expenses 35,182 23,114 89,832 81,987 Loss from operations (35,182) (23,114) (89,832) (81,987)Other income, net: Interest income 2,328 1,962 7,544 5,822 Interest expense (82) (106) (265) (339)Other income, net 211 278 453 825 Total other income, net 2,457 2,134 7,732 6,308 Net loss $(32,725) $(20,980) $(82,100) $(75,679)Net loss per share, basic and diluted $(0.79) $(1.05) $(2.04) $(3.83)Weighted average shares of common stock outstanding basic and diluted 41,443,317 20,059,641 40,182,303 19,767,174

SAN FRANCISCO--(BUSINESS WIRE)--InCarda Therapeutics, Inc.: Analysis of the results of the RESTORE-1 Phase 3 trial following its premature termination demonstrated statistically significant cardioversion of PAF with orally inhaled flecainide, providing compelling rationale for the continued development of FlecIH-103 in the target population of PAF patients. — The RESTORE-1 trial was stopped prematurely due to lower-than-expected efficacy and plasma flecainide levels during a blinded review of the data — There were no safety concerns associated with the administration of FlecIH-103 A novel drug delivery platform has shown the potential to enable efficient and reliable delivery of flecainide to the heart through the lung, appropriate for both hospital and home use Bridging Phase 1 study data to date establishes a path for future registration trials Today, InCarda, a privately held biopharmaceutical company developing an inhaled flecainide acetate inhalation solution (FlecIH-103) for the acute conversion of paroxysmal atrial fibrillation (PAF) to sinus rhythm (SR), announced significant progress made on several fronts: 1) Results of the RESTORE-1 Phase 3 trial were presented at the 2024 European Society of Cardiology meeting in London 1 on September 2, 2024, and demonstrated strong “patient proof of concept” data for the safe and effective cardioversion of patients with PAF who were administered inhaled flecainide. These results were particularly striking in light of the fact that the trial was stopped prematurely. 2) Transition to a novel and more efficient drug-delivery platform is supported by recent in vitro and Phase 1 clinical data. 3) Preliminary interim results from a Phase 1 clinical study designed to establish the dose and dosing regimen with the new drug delivery platform warrant continuation of the study for the potential advancement of FlecIH-103 into registrational trials. RESTORE-1 Phase 3 results RESTORE-1 was a randomized, placebo-controlled, Phase 3 trial, employing a commercially available jet nebulizer, to assess the efficacy and safety of FlecIH-103 for the treatment of patients with PAF. The trial was stopped prematurely after 54 of the planned 400 patients had been enrolled due to an unexpectedly low rate of blinded cardioversion compared to the experience in the Phase 2 study (INSTANT). The rate of cardioversion in RESTORE-1 was 31% in the treated group versus 47% in the Phase 2 INSTANT study. This outcome was caused by lower-than-expected flecainide plasma levels and unexpected drug-device incompatibility not previously observed in the Phase 2 clinical trial. The premature halting of the trial was not due to any safety concerns. Despite the early termination of the trial and a small sample size (n=54), an analysis showed that the 31% cardioversion rate was statistically significant in FlecIH-103-treated patients compared to placebo (p=0.04), with a median time to restoration of normal sinus rhythm (NSR) of approximately 13 minutes from the start of dosing. The study captured statistically significant pharmacoeconomic benefits from early restoration of SR following administration of FlecIH-103: a) 80% of patients whose AF converted to sinus rhythm were eligible for discharge from the hospital within 2 hours of dose administration, compared to only 30% of patients whose PAF did not convert (p=0.002) b) 83% of patients who converted from PAF to NSR within 90 min of dosing were symptom-free, while only 28% of patients whose PAF did not convert to SR were symptom-free (p<0.0001) c) The need for electrical cardioversion to restore sinus rhythm was 49% in the active arm vs. 83% in the placebo arm (p<0.05). There were no safety concerns or SAEs associated with the administration of FlecIH-103 in this study and no patients discontinued the study due to an adverse event (AE) or had an AE that required treatment. In summary, these results indicate that orally inhaled flecainide can provide safe and rapid restoration of sinus rhythm in patients presenting to the emergency room with symptomatic acute PAF. We believe FlecIH-103 delivered via oral inhalation has the potential to be clinically meaningful and address the important unmet medical need for the estimated one million U.S. patients who visit ERs with PAF each year. Improved drug-delivery platform The lower-than-expected flecainide plasma levels observed in RESTORE-1 using a jet nebulizer motivated the transition to Aerogen’s novel, high-performance drug-delivery platform that enables more efficient and reliable inhaled delivery of FlecIH-103. This platform includes: a) A novel vibrating-mesh aerosol generation engine proven to deliver drugs to the deep lungs for rapid systemic absorption, provided by Aerogen Ltd., a world leader in acute care aerosol drug delivery located in Galway, Ireland, and b) A unique patient-facing breath-synchronized dosing system that helps optimize the patient’s breathing for the inhalation of FlecIH-103. The Aerogen drug-delivery platform employs the PDAP (Photo Defined Aperture Plate) technology, a breakthrough patented vibrating mesh for medical aerosol delivery developed by Aerogen Ltd. The PDAP technology effectively aerosolizes our flecainide formulation (FlecIH-103) into a fine-mist aerosol. In addition, the patient is guided by the dosing system to synchronize their breathing with the generation of the aerosol. We believe this increases the efficiency of the delivery of FlecIH-103 to the heart and may enable a low nominal dose needed for rapid and safe cardioversion. Bridging Phase 1 clinical data Preliminary interim results from a Phase 1 study being conducted in Australia with FlecIH-103 administered with this new delivery platform show encouraging results: a) Peak flecainide plasma concentrations (C max ) similar to those achieved in the Phase 2 (INSTANT) clinical trial, which showed a conversion rate of ~ 50% b) One-third of the amount of FlecIH-103 was needed in the inhaler to achieve similar C max when compared to the amount needed with the commercial jet nebulizer used in RESTORE-1, and c) Electrocardiographic (ECG) changes that are transient and consistent with the pharmacokinetics (PK) of the inhaled flecainide and are within a safe range [Max ΔQRS duration < 30 msec] No new safety signals have been observed, no SAEs reported and all AEs resolved without sequelae; the FlecIH-103 safety pro consistent with that observed in prior studies. We believe the novel delivery platform will easily be adaptable in all patient care settings including the hospital and at-home settings. Future plans InCarda plans to complete the ongoing Phase 1 study, including the investigation of additional dose regimens such as administration of a booster dose similar to current approved products for treating cardiac arrhythmias. Inhaled flecainide is being developed for use in both a medically supervised setting (e.g., in-hospital, emergency rooms and clinics) and as a portable treatment for self-administration outside the hospital. InCarda plans to reinitiate safety and efficacy trials in patients with PAF in 2025. Dr. Luiz Belardinelli, MD, InCarda’s Chief Medical Officer, said, “We believe that inhaled flecainide has the potential to be a valuable treatment for patients with recent-onset episodes of PAF. While RESTORE-1 did not achieve the level of efficacy desired and the trial was terminated early, the analysis showed a statistically significant higher conversion rate in the active arm compared to the placebo for the 54 patients evaluated, and the continued encouraging safety and tolerability pro FlecIH-103 suggest that this treatment could become an important option for patients with acute episodes of recent-onset of PAF. The trial also indicated that patients whose PAF converted to NSR had their symptoms relieved, required fewer interventions, and were discharged earlier from the ER, thus suggesting attractive pharmacoeconomic benefits of orally inhaled flecainide.” Carlos Schuler, Ph.D., co-founder and CEO of InCarda, said, “I am very excited by the ability of the new drug-delivery platform to deliver flecainide reliably. Given the positive Phase 1 results to date, I am optimistic that we will be able to achieve commercially attractive efficacy and safety and demonstrate pharmacoeconomic benefits in the registrational studies currently being planned.” About Atrial Fibrillation (AF) Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia (abnormal heart rhythm) and is characterized by rapid and irregular heartbeats often resulting in palpitations and other symptoms that can be debilitating. A chronic, progressive condition, AF is estimated to affect six million people in the U.S., with that number expected to double by 2050 2 . This expected increase is partially due to the correlation between AF prevalence and an aging population, with approximately 9% of those aged 65 and older affected by the condition 2 . AF is associated with significant morbidity and a substantial reduction in quality of life, with the condition potentially resulting in exercise intolerance, congestive heart failure, tachycardia-induced cardiomyopathy, and stroke. The annual cost of AF to the U.S. healthcare system is estimated at more than $26 billion 2 . Paroxysmal AF (PAF) is a self-terminating type of AF in which episodes occur intermittently and resolve spontaneously in fewer than seven days. Approximately 25% of PAF patients progress to the permanent form of AF within five years 3 . Common symptoms of PAF can include a racing heartbeat, chest pain or pressure, a fluttering feeling in the chest, weakness, fatigue, dizziness, sweating, and lightheadedness. Current treatments for patients with PAF rely upon either chronic administration of oral antiarrhythmic drugs or acute hospital-based procedures such as intravenous drug administration of rate-control medicines and electrical cardioversion, neither of which adequately address the unmet need of patients for a rapid-acting treatment that can be administered whenever an episode of PAF occurs. There are currently no approved treatments that can be self-administered by patients whenever or wherever an episode of PAF occurs. About Inhaled Flecainide Inhaled Flecainide is a novel inhaled therapeutic candidate designed to rapidly deliver flecainide, a well-established oral antiarrhythmic agent, to the heart via the lungs to restore normal sinus rhythm and relieve the patient’s symptoms following the onset of new or recurrent episodes of paroxysmal AF (PAF). Previously completed Phase 1 clinical studies in healthy volunteers demonstrated that orally inhaled flecainide can rapidly and safely deliver the drug and result in ECG changes consistent with the potential to restore sinus rhythm in patients with PAF. A previously completed Phase 2 trial (INSTANT) in patients with recent-onset PAF showed that inhaled flecainide with an administration regimen of approximately eight minutes can safely and rapidly convert recent-onset PAF to normal sinus rhythm. InCarda started RESTORE-1, a Phase 3 clinical trial, but halted the study as mentioned above. With intellectual property protection now potentially extendable through 2045 with the inclusion of the new delivery system, orally inhaled flecainide continues to have potential as a first-in-class treatment for acute management of PAF. We estimate over a billion-dollar market potential for this product, in addressing this significant unmet medical need. About InCarda Therapeutics InCarda Therapeutics, Inc. is a privately held, clinical-stage biopharmaceutical company developing first-of-their-kind inhaled therapies for acute cardiovascular diseases and conditions. The company is leveraging the ability of inhaled therapy to deliver medicine in the “first pass” to cardiac tissue, presenting a ‘small,’ but effective dose of the drug directly to affected regions of the heart. This permits rapid-onset, lower off-target tissue exposure of the drug, lower exposure to cardiac tissue, and has the potential to be patient self-administered in an ambulatory care setting (e.g., at home care). InCarda employs a de-risked approach by using approved drugs as candidates for the new dosing paradigm via inhalation. The company’s lead development product, orally inhaled flecainide, is in development to treat acute episodes of symptomatic PAF, a prevalent cardiac arrhythmia. For more information, please visit: . LinkedIn: Twitter: @InCardaThera References: RESTORE-1 abstract, Dr. M. Rienstra, MD (Netherlands), ESC, London, Sep 02, 2024 J Am Coll Cardiol. 2014 Dec 2;64(21):2305-7 Am Heart J. 2005 Mar; 149(3):489-96 Contacts Carlos Schuler, Ph.D. CEO and Co-founder Email: schuler.carlos@incardatherapeutics.com Phone: 510-422-5522