UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2022 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number 001-38787 CYCLERION THERAPEUTICS, INC. (Exact Name of Registrant as Specified in its Charter) Massachusetts (State or other jurisdic ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington D.C. 20549 FORM 10-K ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2021 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number: 001-38787 CYCLERION THERAPEUTICS, INC. (Exact Name of registrant as specified in its charter) Massachusetts (State or other jurisdiction of incorpor ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Title of each class Trading Symbol(s) Name of each exchange on which registered Common Stock, no par value CYCN The Nasdaq Stock Market LLC (Nasdaq Global Select Market) FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2021 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transit ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2021 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number 001-38787 CYCLERION THERAPEUTICS, INC. (Exact Name of Registrant as Specified in its Charter) Massachusetts (State or other jurisdict ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2021 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number 001-38787 CYCLERION THERAPEUTICS, INC. (Exact Name of Registrant as Specified in its Charter) Massachusetts (State or other jurisdic ...

[Business Overview](index=5&type=section&id=Item%201.%20Business) Cyclerion Therapeutics, a clinical-stage biopharmaceutical company, focuses on developing CNS treatments, with lead asset CY6463 for MELAS and ADv, and outsources all manufacturing [Research and Development Programs](index=6&type=section&id=Research%20and%20Development%20programs) The company's R&D focuses on CNS programs, led by CY6463 in Phase 2a for MELAS and planned for ADv, while non-CNS assets are available for out-licensing - The lead asset, **CY6463**, a CNS-penetrant sGC stimulator, is in development for serious CNS diseases, with positive Phase 1 results announced in October 2020[24](index=24&type=chunk)[26](index=26&type=chunk) - A **Phase 2a clinical trial in MELAS** has been initiated, and a **Phase 2a trial in ADv** is planned for mid-2021, supported by a **$2 million grant** from the Alzheimer's Association[27](index=27&type=chunk) - Non-CNS assets, **praliciguat and olinciguat**, have completed Phase 2 studies and are available for out-licensing, being outside the company's strategic focus[29](index=29&type=chunk) [Intellectual Property](index=7&type=section&id=Intellectual%20Property) The company protects its technology through owned patents and trade secrets, with CY6463 patents expiring in 2037 and other assets extending into the 2030s - The company owns its intellectual property, comprising **17 issued U.S. patents** and numerous pending applications domestically and abroad[34](index=34&type=chunk)[35](index=35&type=chunk) - The **CY6463 patent portfolio** includes two issued U.S. patents covering the compound and compositions, expiring in **2037**[37](index=37&type=chunk)[38](index=38&type=chunk) - The **praliciguat and olinciguat patent portfolios** include multiple U.S. patents expiring between **2031 and 2037**[40](index=40&type=chunk)[41](index=41&type=chunk)[44](index=44&type=chunk) [Government Regulation](index=10&type=section&id=Government%20Regulation) The company's drug development is subject to extensive FDA regulation, involving nonclinical studies, INDs, multi-phase clinical trials, NDA submission, and post-approval compliance, with potential for expedited review designations - The drug approval process requires extensive nonclinical studies, an IND submission, and multi-phase clinical trials to establish safety and efficacy before NDA submission to the FDA[54](index=54&type=chunk)[59](index=59&type=chunk) - The FDA offers programs like **Fast Track, Breakthrough Therapy, Accelerated Approval, and Priority Review** to expedite development and review for serious conditions[69](index=69&type=chunk)[71](index=71&type=chunk)[72](index=72&type=chunk) - **Orphan Drug Designation** provides **seven years of market exclusivity** for drugs treating rare diseases affecting fewer than **200,000 people** in the U.S[67](index=67&type=chunk)[68](index=68&type=chunk) - Post-approval, the company is subject to ongoing FDA regulation, including recordkeeping, adverse event reporting, and **cGMP compliance**[79](index=79&type=chunk)[80](index=80&type=chunk) [Competition](index=15&type=section&id=Competition) The company faces significant competition, primarily from Bayer/Merck in sGC modulators, and from companies developing treatments for MELAS and Alzheimer's Disease, where no specific ADv treatments are approved - The primary competitor in the sGC modulator space is the **Bayer/Merck collaboration**, with two approved non-CNS products, **ADEMPAS® and VERQUVO®**[96](index=96&type=chunk) - For MELAS, there are no approved treatments, but competitors in clinical development include **PTC Therapeutics, Khondrion B.V, and Abliva AB**[92](index=92&type=chunk) - For ADv, there are no approved treatments, but competition includes approved AD symptom treatments and late-stage AD candidates from companies like **Biogen, Eli Lilly, and Roche**[93](index=93&type=chunk)[95](index=95&type=chunk) [Manufacturing and Human Capital](index=17&type=section&id=Manufacturing) The company outsources all manufacturing to third-party CMOs and, as of December 31, 2020, had approximately 34 employees after a workforce reduction - The company relies entirely on **third-party contract manufacturing organizations (CMOs)** for all clinical and nonclinical supply needs, owning no manufacturing facilities[98](index=98&type=chunk) - As of **December 31, 2020**, the company had approximately **34 employees**, with an additional **17 employees transitioning out** in Q1 2021 due to a 2020 workforce reduction[102](index=102&type=chunk) [Risk Factors](index=18&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant risks including financial losses, high CNS drug development failure rates, clinical trial delays, regulatory uncertainties, heavy reliance on third parties, and post-separation tax and strategic restrictions [Financial Position and Capital Needs](index=20&type=section&id=Risks%20Related%20to%20Our%20Financial%20Position%20and%20Capital%20Needs) As a clinical-stage company with no product revenue, Cyclerion has incurred significant net losses and will require substantial additional funding to advance its pipeline - The company is a clinical-stage biopharmaceutical company with no approved products and has never generated revenue from product sales[120](index=120&type=chunk) Net Loss | Fiscal Year | Net Loss (in millions USD) | | :--- | :--- | | 2020 | $77.8 | | 2019 | $123.0 | - As of **December 31, 2020**, the company had approximately **$54.4 million in cash and cash equivalents** and will require significant additional funding[128](index=128&type=chunk) [Business and Industry Risks](index=21&type=section&id=Risks%20Related%20to%20our%20Business%20and%20Industry) The company faces inherent risks in CNS drug development due to biological complexities, high clinical trial failure rates, potential COVID-19 disruptions, and the lengthy, unpredictable regulatory approval process - CNS therapy development is challenging due to the **blood-brain barrier** and often poor translatability from nonclinical to clinical results[132](index=132&type=chunk) - The **COVID-19 pandemic** continues to risk disrupting clinical development, potentially delaying patient enrollment and trial execution[137](index=137&type=chunk)[138](index=138&type=chunk) - The regulatory approval process is lengthy and unpredictable, with no guarantee of product candidate approval[143](index=143&type=chunk)[144](index=144&type=chunk) [Reliance on Third Parties](index=26&type=section&id=Risks%20Related%20to%20Our%20Reliance%20on%20Third%20Parties) The company's business model heavily relies on third parties for out-licensing, clinical trials (CROs), and manufacturing (CMOs), posing risks to performance, quality, and regulatory compliance due to less direct control - Failure to find a partner for out-licensing **praliciguat** would adversely affect the prospect of realizing financial benefit from the asset[160](index=160&type=chunk) - The company relies on **third-party CROs** for clinical studies and **CMOs** for drug manufacturing, depending on their performance and compliance with regulations like GCP and cGMP[164](index=164&type=chunk)[170](index=170&type=chunk)[171](index=171&type=chunk) - Reliance on third parties necessitates sharing confidential information and trade secrets, increasing the risk of misappropriation or unauthorized disclosure[174](index=174&type=chunk)[175](index=175&type=chunk) [Risks Related to the Separation from Ironwood](index=43&type=section&id=Risks%20Related%20to%20the%20Separation) The 2019 separation from Ironwood poses risks including unrepresentative historical financials, potential IRS challenge to tax-free status leading to significant indemnification liabilities, and restrictions on strategic transactions - Historical financial information may not be representative of future results due to expense allocations from Ironwood prior to the separation[286](index=286&type=chunk)[287](index=287&type=chunk) - If the separation from Ironwood is deemed taxable, Cyclerion could be required to indemnify Ironwood for significant, uncapped tax liabilities[288](index=288&type=chunk)[294](index=294&type=chunk) - To preserve tax-free status, the tax matters agreement prohibits Cyclerion from certain transactions, like a **3% or more change of ownership**, for two years post-distribution[295](index=295&type=chunk) [Management's Discussion and Analysis (MD&A)](index=51&type=section&id=Item%207.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations.) This section provides management's analysis of the company's financial condition and results for 2020 versus 2019, highlighting decreased operating expenses, sufficient cash for 12 months, and details on R&D and liquidity sources [Results of Operations (2020 vs. 2019)](index=55&type=section&id=Results%20of%20Operations) In fiscal year 2020, the company reported a net loss of $77.8 million, a 37% improvement from 2019, driven by significant reductions in R&D and G&A expenses, and gains from lease modifications Key Financial Metrics | Financial Metric | 2020 (in thousands USD) | 2019 (in thousands USD) | Change ($ in thousands USD) | Change (%) | | :--- | :--- | :--- | :--- | :--- | | Revenue from related party | $2,296 | $4,507 | $(2,211) | (49)% | | Research and development | $56,414 | $95,140 | $(38,726) | (41)% | | General and administrative | $28,816 | $34,404 | $(5,588) | (16)% | | **Net loss** | **$(77,802)** | **$(123,008)** | **$45,206** | **(37)%** | R&D External Costs by Program | R&D External Costs by Program | 2020 (in thousands USD) | 2019 (in thousands USD) | | :--- | :--- | :--- | | CY6463 | $5,561 | $4,278 | | Praliciguat | $311 | $13,344 | | Olinciguat | $6,868 | $13,064 | | Discovery research | $1,218 | $1,293 | - The decrease in R&D expenses was primarily due to reduced spending on **praliciguat studies (down $13.0 million)** and **olinciguat studies (down $6.2 million)**, alongside lower personnel and facility costs[363](index=363&type=chunk) - The company recorded a **net gain on lease modification of $1.7 million** and **sublease termination income of $2.9 million** in 2020[365](index=365&type=chunk)[367](index=367&type=chunk) [Liquidity and Capital Resources](index=56&type=section&id=Liquidity%20and%20Capital%20Resources) As of December 31, 2020, the company held $54.4 million in cash, which management deems sufficient for the next 12 months, following 2020 financing activities including a private placement and a PPP loan - The company had **$54.4 million in unrestricted cash and cash equivalents** as of **December 31, 2020**[373](index=373&type=chunk) - Management concluded that existing cash and cash equivalents are sufficient to fund planned operations for at least the **next 12 months** from the report filing date[374](index=374&type=chunk)[387](index=387&type=chunk) - In 2020, the company raised approximately **$24.3 million** via a private placement, received a **$3.5 million PPP loan**, and established a **$50.0 million ATM offering**[370](index=370&type=chunk)[371](index=371&type=chunk)[382](index=382&type=chunk) Cash Flow Summary | Cash Flow Summary | 2020 (in thousands USD) | 2019 (in thousands USD) | | :--- | :--- | :--- | | Net cash used in operating activities | $(72,490) | $(102,215) | | Net cash provided by (used in) investing activities | $18 | $(6,715) | | Net cash provided by financing activities | $28,090 | $211,571 | [Controls and Procedures](index=60&type=section&id=Item%209A.%20Controls%20and%20Procedures.) Management concluded that the company's disclosure controls and internal control over financial reporting were effective as of December 31, 2020, with no auditor attestation required for an emerging growth company - Management concluded that the company's **disclosure controls and procedures were effective** as of **December 31, 2020**[408](index=408&type=chunk) - Based on its assessment, management concluded that the company's **internal control over financial reporting was effective** as of **December 31, 2020**[413](index=413&type=chunk) - This annual report does not include an auditor's attestation report on internal control over financial reporting, as permitted for **"emerging growth companies"**[415](index=415&type=chunk) [Financial Statements and Notes](index=66&type=section&id=Item%208.%20Financial%20Statements%20and%20Supplementary%20Data.) This section presents the company's audited consolidated financial statements for 2020 and 2019, along with detailed notes on accounting policies, the Ironwood separation impact, lease modifications, share-based compensation, income taxes, and workforce reductions [Consolidated Financial Statements](index=68&type=section&id=Consolidated%20Financial%20Statements) As of December 31, 2020, the company reported total assets of $115.4 million, total liabilities of $55.9 million, a net loss of $77.8 million, and $72.5 million in net cash used in operating activities Balance Sheet Highlights (Dec 31, 2020) | Balance Sheet Highlights (Dec 31, 2020) | Amount (in thousands USD) | | :--- | :--- | | Cash and cash equivalents | $54,395 | | Total assets | $115,378 | | Total liabilities | $55,885 | | Total stockholders' equity | $59,493 | Statement of Operations Highlights (FY 2020) | Statement of Operations Highlights (FY 2020) | Amount (in thousands USD) | | :--- | :--- | | Total cost and expenses | $83,561 | | Loss from operations | $(81,265) | | Net loss | $(77,802) | | Net loss per share | $(2.56) | [Selected Notes to Financial Statements](index=72&type=section&id=Selected%20Notes%20to%20Financial%20Statements) Key financial notes confirm no substantial doubt about going concern, detail 2020 lease amendments yielding $1.7 million gain and $2.9 million income, describe a $5.0 million workforce reduction, and disclose fully offset NOL carryforwards - Management concluded no substantial doubt exists regarding the company's ability to continue as a **going concern** for at least one year from the financial statements' issuance[486](index=486&type=chunk)[488](index=488&type=chunk) - In 2020, two lease amendments resulted in a **net gain on modification of $1.7 million**, and a sublease termination generated **$2.9 million in net income**[518](index=518&type=chunk)[519](index=519&type=chunk)[520](index=520&type=chunk) - A **workforce reduction** in November 2020 impacted approximately **48 employees** with an estimated cost of **$5.0 million**[629](index=629&type=chunk)[630](index=630&type=chunk) - As of **December 31, 2020**, the company had federal and state **NOL carryforwards** of approximately **$98.8 million and $98.9 million**, respectively, fully offset by a valuation allowance[618](index=618&type=chunk)[620](index=620&type=chunk)

Research and Development Expenses - The company reported research and development expenses of $13.703 million for the three months ended September 30, 2020, compared to $22.295 million for the same period in 2019, representing a decrease of approximately 38.8%[152] - For the nine months ended September 30, 2020, total research and development expenses were $44.322 million, down from $74.458 million in 2019, indicating a reduction of about 40.5%[152] - The external costs related to the IW-6463 product pipeline were $1.502 million for the three months ended September 30, 2020, compared to $1.559 million in 2019, showing a slight decrease of 3.6%[152] - Olinciguat, another product candidate, incurred external costs of $2.012 million for the three months ended September 30, 2020, down from $2.891 million in 2019, reflecting a decrease of approximately 30.3%[152] - Praliciguat's external costs were $53,000 for the three months ended September 30, 2020, significantly lower than $2.575 million in the same period of 2019, indicating a decrease of about 98%[152] - The company reported total product pipeline external costs of $4.108 million for the three months ended September 30, 2020, compared to $7.389 million in 2019, a decrease of approximately 44.5%[152] - Personnel and related internal costs allocated to research and development were $6.214 million for the three months ended September 30, 2020, down from $9.517 million in 2019, a reduction of about 34.5%[152] - Facilities and other costs related to research and development were $3.381 million for the three months ended September 30, 2020, compared to $5.389 million in 2019, representing a decrease of approximately 37.2%[152] - Research and development expenses decreased by approximately $8.6 million (39%) for the three months ended September 30, 2020, and by approximately $30.1 million (40%) for the nine months ended September 30, 2020, primarily due to lower average headcount and reduced external research costs[167][168] Clinical Trials and Product Development - The company plans to begin enrolling participants in the Phase 2 clinical trial for MELAS and aims to initiate a Phase 2 trial for Alzheimer's disease with vascular pathology in H1 2021[147] - As of September 30, 2020, the company had ongoing studies in various clinical trial stages, with significant spending on clinical research organizations[202] Financial Performance - Net loss for the three months ended September 30, 2020 was $18.8 million, a decrease of $8.5 million (31%) compared to the same period in 2019, and for the nine months ended September 30, 2020, the net loss was $58.6 million, a decrease of $38.4 million (40%) compared to the prior year[166] - Cash provided by financing activities for the nine months ended September 30, 2020 was $27.9 million, a significant decrease of $183.5 million (87%) compared to $211.4 million in the same period in 2019[186] - Net cash used in operating activities was $58.4 million for the nine months ended September 30, 2020, a decrease of $21.6 million (27%) compared to the same period in 2019[186] Cash and Funding - As of September 30, 2020, the company had approximately $66.8 million of unrestricted cash and cash equivalents, which are expected to fund operations into the fourth quarter of 2021[183][184] - The company raised approximately $24.3 million in a private placement of common stock on July 29, 2020, with no material fees or commissions related to the transaction[180] - The company anticipates principal uses of cash in the future will be to fund operations, working capital needs, capital expenditures, and other general corporate purposes[182] - The company received approximately $3.5 million in loan proceeds under the Paycheck Protection Program with a stated interest rate of 1.0% per annum[190] - The loan's principal and accrued interest are forgivable if proceeds are used for eligible purposes and payroll levels are maintained over a 24-week period[191] - As of September 30, 2020, the company expects existing cash and cash equivalents to fund planned operating expenses at least into Q4 2021[193] - Future funding requirements may fluctuate significantly based on the scope and costs of research and development activities[194] - The company may need to finance cash needs through public or private equity offerings, debt financings, or collaborations[198] General and Administrative Expenses - General and administrative expenses increased by approximately $0.9 million (13%) for the three months ended September 30, 2020, but decreased by approximately $5.5 million (20%) for the nine months ended September 30, 2020, mainly due to non-recurring costs associated with the Separation recorded in the prior period[170][171] Operational Changes - The company incurred additional ongoing operating expenses to operate as an independent publicly traded company following the Separation[203] - The Ironwood Transition Services Agreement, which provided corporate functions, was completed and terminated as of March 31, 2020[206] Risk and Compliance - The company emphasizes that securing regulatory approvals for new drugs is a lengthy and costly process, and any delays could materially affect product development efforts[152] - The company does not have off-balance sheet arrangements that expose it to financing, liquidity, market, or credit risk[208] - The company is classified as a smaller reporting company and is not required to provide certain market risk disclosures[210]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Title of each class Trading Symbol(s) Name of each exchange on which registered Common Stock, no par value CYCN The Nasdaq Stock Market LLC (Nasdaq Global Select Market) FORM 10-Q (Mark One) x QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2020 or ¨ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition p ...

Research and Development Expenses - Research and development expenses for Q1 2020 totaled $16.825 million, a decrease of 36.5% from $26.404 million in Q1 2019[133] - Research and development expenses decreased by approximately $9.6 million to $16.8 million for the three months ended March 31, 2020, a reduction of 36% compared to $26.4 million in the prior year[148] External Costs - Olinciguat incurred external costs of $2.626 million in Q1 2020, down from $3.971 million in Q1 2019[133] - Praliciguat external costs were $135, significantly lower than $5.738 million in Q1 2019[133] - IW-6463 external costs increased to $1.338 million in Q1 2020 from $461 thousand in Q1 2019[133] - Total product pipeline external costs for Q1 2020 were $4.112 million, a reduction of 61.6% compared to $10.704 million in Q1 2019[133] Personnel and Facilities Costs - Personnel and related internal costs for Q1 2020 were $7.737 million, down from $9.758 million in Q1 2019[133] - Facilities and other costs decreased to $4.976 million in Q1 2020 from $5.942 million in Q1 2019[133] Clinical Studies and Development - The company is conducting a Phase 2 study, STRONG-SCD, for Olinciguat with 70 participants enrolled, expecting topline data in Q3 2020[122] - IW-6463 showed positive top-line results in its first-in-human study, demonstrating penetration across the blood-brain barrier[127] - The company is exploring out-licensing opportunities for praliciguat for late-stage global development and commercialization[126] Financial Performance - Revenue from related party for the three months ended March 31, 2020 was $1,014,000, compared to $0 for the same period in 2019, representing a change of 100%[147] - General and administrative expenses decreased by approximately $4.1 million to $6.9 million for the three months ended March 31, 2020, a reduction of 37% compared to $11.0 million in the prior year[149] - The company recorded a gain on lease modification of $2.1 million for the three months ended March 31, 2020, reflecting a 100% change from $0 in the prior year[150] - Net loss for the three months ended March 31, 2020 was $20.2 million, a decrease of 46% from a net loss of $37.4 million in the same period in 2019[147] - Net cash used in operating activities was $29.2 million for the three months ended March 31, 2020, a decrease of 15% from $34.3 million in the prior year[160] - The company had approximately $67.1 million of unrestricted cash and cash equivalents as of March 31, 2020[155] - The company expects existing cash and cash equivalents will be sufficient to fund planned operating expenses into the second quarter of 2021[157] - Cash provided by financing activities was de minimis for the three months ended March 31, 2020, compared to $36.1 million in the prior year[162] - The company anticipates fluctuations in expenses as it advances preclinical activities and clinical trials of its product candidates[163]

Product Development and Pipeline - The company is focused on developing next-generation soluble guanylate cyclase (sGC) stimulators for serious and orphan diseases, aiming to unlock the therapeutic potential of the nitric oxide-cGMP pathway [24]. - The company has five differentiated sGC stimulator programs in its pipeline, with ongoing development phases subject to change due to inherent risks [25]. - Olinciguat is in a Phase 2 study for sickle cell disease (SCD), with results expected in mid-2020, targeting approximately 100,000 patients in the U.S. and 50,000 in the EU5 [27]. - Praliciguat, an oral sGC stimulator, is being evaluated for diabetic nephropathy and heart failure with preserved ejection fraction, with Phase 2 results indicating trends towards improvement in secondary measures despite not meeting primary endpoints [30][31]. - IW-6463 is being developed for neurodegenerative diseases, with positive Phase 1 results indicating good tolerability and pharmacokinetic support for once-daily dosing [35]. - The company aims to complete the STRONG-SCD study for olinciguat and deliver results in mid-2020 to facilitate advancement to Phase 3 [39]. - The topline results from Phase 2 trials of praliciguat did not meet statistical significance for primary endpoints, leading to a decision not to continue development in HFpEF [136]. - The company intends to pursue an out-license of praliciguat for diabetic nephropathy despite the trial results showing trends towards improvement [136]. - The company is developing a pipeline of sGC stimulators, with praliciguat, olinciguat, and IW-6463 as lead candidates [122]. Intellectual Property and Patent Portfolio - The company has a robust intellectual property portfolio, including twelve issued U.S. patents and numerous pending applications as of February 10, 2020 [43]. - The olinciguat patent portfolio includes four U.S. patents, with one expiring in 2034, and additional applications that may extend protection until 2037 or later [46][48]. - The praliciguat patent portfolio includes four U.S. patents, with one expiring in 2034, and pending applications that may extend protection until 2036 or later [50][52]. - The term of individual patents is generally 20 years from the earliest filing date, with potential extensions under specific conditions [60]. - U.S. patents covering FDA-approved drugs may receive extensions of up to five years or 14 years from FDA approval under the Hatch-Waxman Act [62]. - The company has twelve issued U.S. patents and nineteen pending U.S. patent applications as of February 10, 2020, with patents covering olinciguat and praliciguat expiring between 2031 and 2034 [179]. - The company’s issued patent for IW-6463 expires in 2037, with pending applications potentially extending protection beyond that date [179]. - The company may face challenges in enforcing its intellectual property rights, which could lead to increased costs and potential loss of patent protection [182]. - The company’s patent applications may not be granted, and even if granted, they may not provide sufficient protection against competitors [181]. - The company may not pursue patent protection in all jurisdictions, potentially allowing competitors to use its technologies in unprotected areas [201]. - Non-compliance with patent agency requirements could result in the loss of patent rights, adversely affecting the company’s market position [199]. - The company faces significant challenges in enforcing intellectual property rights in foreign jurisdictions, particularly in developing countries where patent protection is limited [203]. - Enforcement proceedings for patent rights in foreign jurisdictions could lead to substantial costs and divert focus from core business activities, potentially risking patent validity [205]. - The company may not obtain additional protection under the Hatch-Waxman Act, which could materially harm its business and financial condition [206]. - A maximum of five years can be restored to eligible patents under the Hatch-Waxman Act, but failure to meet application deadlines could result in loss of patent term extensions [207]. - Changes in U.S. patent law, such as the America Invents Act, could increase uncertainties and costs related to patent prosecution and enforcement [209]. - The company may face claims regarding the wrongful use of trade secrets, which could lead to substantial litigation costs and distract management [210]. Regulatory Environment and Compliance - The FDA's approval process for drugs involves extensive pre-clinical and clinical trials, requiring significant time and financial resources [67]. - Clinical trials are conducted in three phases, with Phase 3 trials involving larger participant groups to demonstrate product effectiveness and safety [72][73]. - The FDA has ten months to review standard NDAs and six months for priority reviews, although these timelines may be extended [77]. - Orphan drug designation can provide exclusivity for seven years post-approval for drugs treating rare diseases affecting fewer than 200,000 individuals in the U.S. [83]. - The FDA offers expedited review programs for drugs addressing serious conditions, including fast track and breakthrough therapy designations [85][86]. - Accelerated approval may be granted based on surrogate endpoints that predict clinical benefit, with confirmatory studies required post-approval [88]. - Compliance with FDA regulations is critical, as failure to meet requirements can lead to sanctions, including product recalls and withdrawal of approvals [64]. - The company is subject to ongoing FDA regulation post-approval, including requirements for recordkeeping, periodic reporting, and product sampling [93]. - The company relies on third-party contract research organizations (CROs) for clinical studies, which may lead to challenges in meeting regulatory requirements [165]. - Changes in regulatory requirements or unexpected events during clinical studies may increase costs and delay timelines [152]. - The company may face significant delays and costs in obtaining foreign regulatory approvals, impacting product introduction [157]. - Regulatory approval in one jurisdiction does not guarantee approval in others, which could negatively impact market potential [155]. - Relationships with third-party CROs are critical, and any failure in their performance could delay regulatory approval and commercialization [170]. - The company is responsible for ensuring compliance with good clinical practices (GCPs) during clinical studies, with potential penalties for non-compliance [168]. Financial Performance and Funding - The company reported net losses of $115.3 million and $123.0 million for the years ended December 31, 2018 and 2019, respectively [124]. - As of December 31, 2019, the company had approximately $94.9 million in unrestricted cash and cash equivalents, expected to fund operations through Q1 2021 [128]. - The company has no products approved for commercial sale and has never generated revenue from product sales [123]. - The company anticipates incurring significant losses for several years as it continues research and development activities [124]. - The company is seeking additional funding through collaborations, strategic alliances, or licensing arrangements to advance product candidates [130]. Market and Competitive Landscape - The biopharmaceutical industry is highly competitive, with many companies actively engaged in similar product development, which may increase competition for the company's product candidates [105]. - The company is aware of several competitors in the sickle cell disease (SCD) treatment space, including Novartis and AstraZeneca, which are developing products in late-stage clinical trials [109]. - The company has identified four approved products in the U.S. for diabetic nephropathy (DN), including AVAPRO® and COZAAR® [111]. - The incidence and prevalence of target patient populations for product candidates are not precisely established, which could harm revenue and profitability if market opportunities are smaller than estimated [213]. - The company lacks an infrastructure for sales and marketing of pharmaceutical products, which could hinder commercialization efforts if not addressed [216]. - Market acceptance of product candidates will depend on various factors, including efficacy, safety, and reimbursement, which are critical for generating sufficient revenue [220]. - Limited reimbursement or price controls in certain markets could adversely affect the company's ability to sell products profitably [222]. Manufacturing and Supply Chain - The company relies on third-party contract manufacturing organizations (CMOs) for all raw materials and drug products, ensuring compliance with current GMP requirements [114]. - The company currently relies on third-party contract manufacturing organizations (CMOs) for all raw materials and drug products for ongoing clinical trials, lacking long-term supply agreements [172]. - The company is subject to price fluctuations for clinical drug supplies from CMOs, which could materially harm its business if prices increase [172]. - The company must share confidential information with third parties, increasing the risk of misappropriation or disclosure of trade secrets [175]. - The company’s ability to protect its proprietary technology and maintain issued patents is critical for its competitive position and financial health [178].