Table of Contents TRANSCODE THERAPEUTICS, INC. UNITED STATES SECURITIES AND EXCHANGE COMMISSION (Exact Name of Registrant as Specified in Its Charter) __________________________________________ Washington, D.C. 20549 ____________________________________________ FORM 10-Q ____________________________________________ ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 Delaware (State or Other Jurisdiction of Incorporation or Organization) 6 Liberty Square, #2382 Boston, M ...

Company Overview - TransCode Therapeutics, Inc. is a clinical-stage oncology company focused on developing RNA-targeted therapeutics for cancer treatment [1][4] - The company aims to combat metastatic disease through the intelligent design and effective delivery of RNA therapeutics using its proprietary TTX nanoparticle platform [4] Key Appointment - Dr. Phillip D. Zamore has been appointed to the Scientific Advisory Board of TransCode Therapeutics [1] - Dr. Zamore is recognized for his pioneering work in RNA interference (RNAi) and co-founded Alnylam Pharmaceuticals, which developed the first FDA-approved RNAi drug [1][6] Research Contributions - Dr. Zamore's research has advanced the understanding of non-coding RNA and its implications in health and disease, particularly in the processing of microRNAs [2] - His contributions have earned him recognition from prestigious institutions, including the National Academy of Sciences and the National Academy of Medicine [2] Strategic Vision - The company emphasizes the importance of Dr. Zamore's expertise in RNA biology to enhance its pipeline of RNA-targeted cancer therapies [3] - Dr. Zamore expressed enthusiasm for contributing to the development of effective RNA-based treatments for cancer patients [3] Product Focus - TransCode's lead therapeutic candidate, TTX-MC138, targets metastatic tumors that overexpress microRNA-10b, a biomarker associated with metastasis [4] - The company has a portfolio of first-in-class RNA therapeutic candidates aimed at overcoming RNA delivery challenges to access novel genetic targets for various cancers [4]

[PART I. FINANCIAL INFORMATION](index=8&type=section&id=PART%20I.%20FINANCIAL%20INFORMATION) [Financial Statements](index=8&type=section&id=ITEM%201.%20FINANCIAL%20STATEMENTS) This section presents the unaudited consolidated financial statements for TransCode Therapeutics, Inc. for the quarter ended March 31, 2025, reflecting a significant net loss and reliance on equity financing [Balance Sheets](index=8&type=section&id=BALANCE%20SHEETS) As of March 31, 2025, the company's total assets increased to approximately $13.2 million from $7.3 million at year-end 2024, primarily due to a rise in cash from financing activities, leading to a positive stockholders' equity of $10.3 million from a $2.0 million deficit Balance Sheet Summary (Unaudited) | Account | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash | $11,569,154 | $5,811,064 | | Total current assets | $13,044,388 | $7,093,338 | | **Total assets** | **$13,194,375** | **$7,294,499** | | **Liabilities & Equity** | | | | Total current liabilities | $2,509,677 | $2,771,836 | | Total liabilities | $2,901,677 | $9,313,233 | | Total stockholders' equity (deficit) | $10,292,698 | $(2,018,734) | | **Total liabilities and stockholders' equity (deficit)** | **$13,194,375** | **$7,294,499** | [Statements of Operations](index=9&type=section&id=STATEMENTS%20OF%20OPERATIONS) For the three months ended March 31, 2025, the company reported a net loss of $12.1 million, a significant increase from the $3.3 million net loss in the same period of 2024, primarily driven by a $9.2 million non-cash charge related to the change in fair value of warrant liability Statement of Operations Summary (Unaudited, in thousands) | Line Item | Three Months Ended Mar 31, 2025 | Three Months Ended Mar 31, 2024 | | :--- | :--- | :--- | | Research and development | $2,219.5 | $1,759.0 | | General and administrative | $951.7 | $1,530.0 | | **Total operating expenses** | **$3,171.2** | **$3,289.0** | | Operating loss | $(3,171.2) | $(3,289.0) | | Change in fair value of warrant liability | $(9,234.9) | $0 | | Grant income | $347.8 | $27.1 | | **Net loss** | **$(12,085.4)** | **$(3,326.8)** | | **Net loss per share** | **$(2.51)** | **$(21.35)** | [Statements of Stockholders' Equity (Deficit)](index=10&type=section&id=STATEMENTS%20OF%20STOCKHOLDERS%27%20EQUITY%20%28DEFICIT%29) During the first quarter of 2025, stockholders' equity increased from a deficit of $2.0 million to a positive $10.3 million, primarily due to $8.9 million in net proceeds from common stock issuance and a $15.4 million non-cash contribution from warrant exercises, offsetting the $12.1 million net loss - The company transitioned from a stockholders' deficit of **($2,018,734)** at the end of 2024 to a positive equity of **$10,292,698** by March 31, 2025[22](index=22&type=chunk) - Key activities impacting equity in Q1 2025 included a net loss of **($12,085,413)**, offset by **$8,854,797** from common stock issuances and a **$15,384,319** non-cash impact from the exercise of Series D warrants[22](index=22&type=chunk) [Statements of Cash Flows](index=11&type=section&id=STATEMENTS%20OF%20CASH%20FLOWS) For the first quarter of 2025, net cash used in operating activities was $3.1 million, with $8.9 million generated from financing activities, resulting in a net increase in cash of $5.8 million and a period-end balance of $11.6 million Cash Flow Summary (Unaudited, in thousands) | Activity | Three Months Ended Mar 31, 2025 | Three Months Ended Mar 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(3,097) | $(3,937) | | Net cash used in investing activities | $0 | $(4) | | Net cash provided by financing activities | $8,855 | $6,087 | | **Net change in cash** | **$5,758** | **$2,146** | | **Cash, end of period** | **$11,569** | **$4,914** | [Notes to Financial Statements](index=12&type=section&id=NOTES%20TO%20FINANCIAL%20STATEMENTS) The notes provide critical context to the financial statements, detailing the company's business, liquidity challenges, significant accounting policies, recent equity financings, and subsequent events including a planned reverse stock split and Nasdaq delisting notice - The company has concluded there is substantial doubt about its ability to continue as a going concern, as existing cash is not sufficient to fund operations for a full 12 months from the financial statement issuance date[33](index=33&type=chunk) - In March 2025, the company raised approximately **$8.9 million** in net proceeds through a best efforts public offering of common stock and warrants[116](index=116&type=chunk) - Subsequent to the quarter end, the company received a delisting notice from Nasdaq for failing to meet the minimum bid price requirement and approved a **1-for-28** reverse stock split expected to be effective May 15, 2025[156](index=156&type=chunk)[157](index=157&type=chunk) - During Q1 2025, all Series D warrants were exercised, resulting in the issuance of **11,925,041 shares** after reset adjustments and a non-cash charge of **$9.2 million** to the change in fair value of warrant liability[80](index=80&type=chunk)[134](index=134&type=chunk)[212](index=212&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=45&type=section&id=ITEM%202.%20MANAGEMENT%27S%20DISCUSSION%20AND%20ANALYSIS%20OF%20FINANCIAL%20CONDITION%20AND%20RESULTS%20OF%20OPERATIONS) Management discusses the company's business strategy, focusing on its RNA therapeutic delivery platform and lead candidate TTX-MC138, detailing recent developments, financial results, and liquidity challenges, concluding there is substantial doubt about its ability to continue as a going concern [Company and Technology Overview](index=45&type=section&id=Company%20and%20Technology%20Overview) TransCode is a biopharmaceutical company focused on defeating cancer through RNA therapeutics, with its proprietary TTX delivery platform and lead candidate TTX-MC138, currently in a Phase I/II clinical trial - The company's lead therapeutic candidate, **TTX-MC138**, targets **miRNA-10b**, a key regulator of metastasis in various cancers[159](index=159&type=chunk) - The proprietary **TTX delivery platform** is designed to improve stability, efficiency, and tumor targeting of RNA therapeutics compared to existing lipid-based systems[164](index=164&type=chunk) - A **Phase I/II clinical trial** for TTX-MC138 commenced in the third quarter of 2024 after receiving an IND 'Study May Proceed' notification from the FDA[159](index=159&type=chunk) [Recent Developments and Financial Overview](index=51&type=section&id=Recent%20Developments%20and%20Financial%20Overview) Key recent events include advancing the Phase I/II clinical trial for TTX-MC138, securing approximately $10 million in equity financing, and receiving a Nasdaq delisting notice, with the company facing an accumulated deficit of $75.3 million - The Phase 1a clinical trial is progressing, with the Safety Review Committee (SRC) approving dose escalation up to the fourth cohort and noting no drug-related serious adverse effects or dose-limiting toxicities in the first three cohorts[179](index=179&type=chunk) - In March 2025, the company closed a registered direct offering, raising gross proceeds of approximately **$10 million**[180](index=180&type=chunk) - On May 7, 2025, the company received a delisting notice from Nasdaq for not meeting the **$1.00** minimum bid price requirement and intends to appeal the determination[182](index=182&type=chunk) [Results of Operations](index=62&type=section&id=Results%20of%20Operations) Comparing Q1 2025 to 2024, R&D expenses increased by $0.5 million due to clinical trial costs, G&A expenses decreased by $0.6 million, and the net loss surged to $12.1 million from $3.3 million, primarily due to a $9.2 million non-cash loss from warrant liability Comparison of Results of Operations (in thousands) | | Three Months Ended March 31, | Change | | :--- | :--- | :--- | :--- | | | **2025** | **2024** | **($)** | | Research and development | $2,220 | $1,759 | $461 | | General and administrative | $952 | $1,530 | $(578) | | **Operating loss** | **$(3,172)** | **$(3,289)** | **$117** | | Change in fair value of warrant liability | $(9,235) | $— | $(9,235) | | **Net loss** | **$(12,085)** | **$(3,327)** | **$(8,759)** | - The increase in R&D expenses was primarily due to start-up costs for the clinical trial[210](index=210&type=chunk) - The significant increase in net loss was mainly due to a **$9.2 million** non-cash loss on the change in fair value of warrant liability, resulting from the exercise of Series D warrants[212](index=212&type=chunk) [Liquidity and Capital Resources](index=64&type=section&id=Liquidity%20and%20Capital%20Resources) The company, historically funded by equity and grants, held $11.6 million in cash as of March 31, 2025, but estimates this is sufficient only into Q4 2025, raising substantial doubt about its going concern ability and necessitating additional capital - As of March 31, 2025, the company had approximately **$11.6 million** in cash[189](index=189&type=chunk)[224](index=224&type=chunk) - Existing cash is projected to fund operating expenses and capital requirements only into the **fourth quarter of 2025**[189](index=189&type=chunk)[226](index=226&type=chunk) - These conditions raise substantial doubt about the company's ability to continue as a going concern, and failure to raise additional capital may force it to delay, reduce, or terminate programs and potentially seek restructuring[226](index=226&type=chunk)[231](index=231&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=76&type=section&id=ITEM%203.%20QUANTITATIVE%20AND%20QUALITATIVE%20DISCLOSURES%20ABOUT%20MARKET%20RISK) The company's market risk exposure is limited, with minimal interest rate risk due to cash holdings in non-interest-bearing accounts and foreign currency exchange risk from Euro-denominated vendor payments, without hedging instruments - The company's primary market risk exposure is foreign exchange rate sensitivity to the Euro for certain vendor purchases, which resulted in a loss of **$27,188** in Q1 2025[263](index=263&type=chunk) - Interest rate risk is considered minimal as cash is held in short-term bank deposits and the company has no significant debt[261](index=261&type=chunk)[262](index=262&type=chunk) [Controls and Procedures](index=77&type=section&id=ITEM%204.%20CONTROLS%20AND%20PROCEDURES) Management concluded that the company's disclosure controls and procedures were not effective as of March 31, 2025, due to identified material weaknesses in internal control over financial reporting, with ongoing remediation efforts - Management concluded that as of March 31, 2025, the company's disclosure controls and procedures were not effective due to existing material weaknesses[267](index=267&type=chunk) - The company is continuing remediation efforts, which include implementing robust accounting policies, engaging additional finance personnel and consultants, implementing new software, and formally documenting and assessing procedures[268](index=268&type=chunk)[269](index=269&type=chunk) [PART II. OTHER INFORMATION](index=79&type=section&id=PART%20II.%20OTHER%20INFORMATION) [Legal Proceedings](index=79&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently a party to any material legal proceedings, with the exception of a disputed claim from an investment bank asserting entitlement to fees, which the company rigorously disputes - The company is not involved in any material legal proceedings, with the exception of a disputed claim for fees by an investment bank[275](index=275&type=chunk) [Risk Factors](index=79&type=section&id=Item%201A.%20Risk%20Factors) This section highlights critical risks facing the company, including potential Nasdaq delisting due to minimum bid price non-compliance and substantial doubt about its ability to continue as a going concern, which could lead to restructuring and total loss for security holders - The company is at risk of being delisted from the Nasdaq Capital Market for failing to meet the minimum **$1.00** bid price requirement. A delisting would severely impact stock liquidity and the ability to raise capital[277](index=277&type=chunk)[279](index=279&type=chunk)[280](index=280&type=chunk) - There is substantial doubt about the company's ability to continue as a going concern. Failure to secure additional funding may lead to a restructuring of liabilities, where holders of common stock would likely suffer a total loss of their investment[282](index=282&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=81&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company reported no unregistered sales of equity securities during the reporting period - None[284](index=284&type=chunk) [Defaults upon Senior Securities](index=83&type=section&id=Item%203.%20Defaults%20upon%20Senior%20Securities) The company reported no defaults upon senior securities - None[287](index=287&type=chunk) [Mine Safety Disclosures](index=83&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company's business - Not applicable[288](index=288&type=chunk) [Other Information](index=83&type=section&id=Item%205.%20Other%20Information) The company did not report any other information for the period - None[289](index=289&type=chunk) [Exhibits](index=83&type=section&id=Item%206.%20Exhibits) This section lists all exhibits filed with the Form 10-Q, including corporate governance documents, financing agreements, and officer certifications - The report includes exhibits such as corporate governance documents, financing agreements, and officer certifications required by the SEC[290](index=290&type=chunk)[291](index=291&type=chunk)

Core Viewpoint - TransCode Therapeutics is advancing its Phase 1a clinical trial for TTX-MC138, a novel RNA therapeutic aimed at treating metastatic cancers, with positive safety and pharmacokinetic data supporting further development [1][3][5]. Group 1: Clinical Trial Progress - The third patient in Cohort 4 has received the initial dose of TTX-MC138, with all cohorts having at least three patients dosed [1]. - A total of 15 patients have been treated across four dose levels (0.8 mg/kg to 4.8 mg/kg), with no significant safety or dose-limiting toxicities reported [2][8]. - Ten patients remain on study, receiving doses every 28 days, with two patients showing stable disease after seven doses over approximately seven months [2][8]. Group 2: Safety and Efficacy Data - Preliminary pharmacokinetic (PK) and pharmacodynamic (PD) analyses indicate a predictable dose-response relationship, with evidence of miR-10b target engagement at 24 hours post-infusion [2][4][8]. - The observed tolerability profile supports the advancement of the trial into the Phase 1b dose expansion stage to further evaluate safety and potential anti-tumor activity [3]. Group 3: About TTX-MC138 - TTX-MC138 is designed to inhibit microRNA-10b, which is implicated in the progression of many metastatic cancers, and has shown promising delivery and activity in preclinical studies [4][7]. - The drug candidate has demonstrated a broad therapeutic window, suggesting potential for effective treatment of metastatic tumors [4]. Group 4: Trial Design - The Phase 1 clinical trial is a multicenter, open-label study aimed at evaluating the safety and tolerability of TTX-MC138 in patients with various metastatic solid cancers [5]. - The trial consists of an initial dose-escalation stage followed by a dose-expansion stage to further assess safety, tolerability, and anti-tumor activity [5].

Core Points - TransCode Therapeutics has announced a 1-for-28 reverse stock split effective at 12:01 a.m. Eastern Standard Time on May 15, 2025, to increase the per share trading price and meet Nasdaq listing requirements [1][2] - The reverse stock split will reduce the number of outstanding shares from approximately 23,341,336 to about 833,620 shares, with no fractional shares issued [2] - The company's CUSIP number will change to 89357L 501 as of the effective time of the reverse stock split [4] Company Overview - TransCode Therapeutics is a clinical-stage oncology company focused on treating metastatic disease through RNA therapeutics, utilizing its proprietary TTX nanoparticle platform [5] - The lead therapeutic candidate, TTX-MC138, targets metastatic tumors that overexpress microRNA-10b, a biomarker associated with metastasis [5] - The company is also developing a portfolio of first-in-class RNA therapeutic candidates aimed at overcoming RNA delivery challenges to access novel genetic targets for cancer treatment [5]

Core Viewpoint - TransCode Therapeutics has announced a 1-for-28 reverse stock split to comply with Nasdaq's minimum bid price requirements, aiming to increase the trading price of its common stock [1][2]. Group 1: Reverse Stock Split Details - The reverse stock split will convert twenty-eight current shares into one new share, reducing the total outstanding shares from approximately 23,341,336 to about 833,620 [2]. - No fractional shares will be issued; instead, stockholders will receive rounding up of fractional shares to the nearest whole number [2]. - Proportional adjustments will be made to the exercise prices of outstanding stock options and warrants, as well as to the shares issued under stock incentive plans [2]. Group 2: Implementation and Process - Vstock Transfer LLC will serve as the exchange agent for the reverse stock split, and stockholders of record will not need to take action to receive their post-split shares [3]. - Stockholders holding shares through banks or brokers will have their positions automatically adjusted, but they may need to check with their respective institutions for specific procedures [3]. - The effective date of the reverse stock split will be announced by the company at least two business days prior to implementation [4]. Group 3: Company Overview - TransCode Therapeutics is a clinical-stage oncology company focused on treating metastatic disease through RNA therapeutics [5]. - The company's lead candidate, TTX-MC138, targets metastatic tumors that overexpress microRNA-10b, a biomarker of metastasis [5]. - TransCode is also developing a portfolio of first-in-class RNA therapeutic candidates aimed at overcoming RNA delivery challenges to access novel genetic targets for cancer treatment [5].

Financial Data and Key Metrics Changes - The proposal for a reverse stock split has been approved by a majority of votes, indicating a strategic move to potentially enhance the stock price and attract more investors [6] - The adjournment proposal was also approved, allowing for further solicitation of proxies if necessary [6] Business Line Data and Key Metrics Changes - No specific financial data or performance metrics for individual business lines were provided during the meeting [7] Market Data and Key Metrics Changes - There was no detailed market data or key metrics discussed in the meeting [7] Company Strategy and Development Direction - The company is focused on clinical trials and is committed to reporting data as it becomes available, emphasizing transparency in their research process [8] - The management is preparing to draw down NIH grant funding in the foreseeable future, indicating ongoing reliance on external funding sources [9] Management Comments on Operating Environment and Future Outlook - Management has not experienced adverse effects from NIH grant funding cuts to date, but they are cautious about future implications [9] - The company is optimistic about the nature of their grant and the timing, although uncertainties remain [9] Other Important Information - The meeting concluded with a commitment to report clinical trial data as expeditiously as possible, highlighting the importance of quality control and safety review processes [8] Q&A Session Summary Question: How often are clinical trial assessments done during the current clinical study? - Management stated that they report data as soon as it is available, emphasizing the need for quality control and committee checks before publishing results [8] Question: Has your NIH grant funding been affected by the recent funding cuts? - Management confirmed that there have been no adverse effects from NIH grant funding so far, but they are preparing to draw down funds soon, with future implications still uncertain [9]

Core Insights - TransCode Therapeutics is advancing its Phase 1a clinical trial of TTX-MC138, a first-in-class therapeutic candidate targeting microRNA-10b, which is believed to play a significant role in metastatic cancer progression [1][4][7] - The trial has treated 13 patients with doses ranging from 0.8 mg/kg to 4.8 mg/kg, with no significant safety issues reported [1][8] - Preliminary pharmacokinetic (PK) and pharmacodynamic (PD) data indicate a favorable profile for TTX-MC138, supporting its progression to the Phase 1b trial [2][3] Company Overview - TransCode Therapeutics focuses on RNA therapeutics for treating metastatic diseases, utilizing its proprietary TTX nanoparticle platform [7] - The lead candidate, TTX-MC138, aims to inhibit microRNA-10b, a biomarker associated with metastasis [7] Clinical Trial Details - The Phase 1 clinical trial is designed as a multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety and tolerability of TTX-MC138 in patients with various metastatic solid cancers [5] - The trial consists of an initial dose-escalation stage followed by a dose-expansion stage, with the primary objective of assessing safety and tolerability [5] Treatment Progress - Eight patients are currently receiving ongoing treatment, with two patients demonstrating stable disease after seven months of treatment [2][8] - The trial has shown a predictable dose-response relationship in PK data, with evidence of target engagement for miR-10b in 5 out of 6 patients analyzed [2][8]

Core Viewpoint - TransCode Therapeutics Inc. (RNAZ) has received an upgrade to a Zacks Rank 2 (Buy) due to an upward trend in earnings estimates, indicating a positive outlook for the company's stock price [1][3]. Earnings Estimates and Stock Price Movement - The Zacks rating system is based on changes in earnings estimates, which are strongly correlated with near-term stock price movements [2][4]. - Rising earnings estimates for TransCode Therapeutics suggest an improvement in the company's underlying business, likely leading to increased stock prices [5]. Zacks Rank System - The Zacks Rank system classifies stocks into five groups based on earnings estimates, with a strong historical performance, particularly for Zacks Rank 1 stocks, which have averaged a +25% annual return since 1988 [7]. - The upgrade of TransCode Therapeutics to a Zacks Rank 2 places it in the top 20% of Zacks-covered stocks, indicating a strong potential for market-beating returns in the near term [10]. Earnings Estimate Revisions - For the fiscal year ending December 2025, TransCode Therapeutics is expected to earn -$1.63 per share, reflecting a 96.5% change from the previous year [8]. - Over the past three months, the Zacks Consensus Estimate for TransCode has increased by 62.7%, highlighting a positive trend in earnings estimates [8].

Financial Position and Capital Requirements - As of December 31, 2024, the company had cash of approximately $5.8 million, which is expected to support operating expenses into the middle of Q2 2025[287]. - The company incurred net losses of approximately $16.8 million and $18.5 million for the years ended December 31, 2024, and 2023, respectively, with an accumulated deficit of approximately $63.2 million as of December 31, 2024[289]. - The company plans to raise additional capital to continue operations, with a net proceeds expectation of approximately $8.8 million from equity financing completed on March 25, 2025[296]. - Future capital requirements will depend on various factors, including the costs of drug discovery, clinical trials, and regulatory reviews[299]. - The company anticipates ongoing significant losses and may not achieve profitability in the foreseeable future due to the speculative nature of oncology product development[288]. - The company may need to seek in-court or out-of-court restructuring of liabilities if unable to raise sufficient capital, which could lead to a total loss of investment for stockholders[287]. Clinical Development and Regulatory Challenges - The company has completed a Phase 0 clinical trial and initiated a Phase I/II study, successfully enrolling 10 patients in four treatment cohorts[288]. - TTX-MC138 is undergoing an open Phase I/II clinical trial designed to assess safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity[323]. - The company has not yet demonstrated the ability to successfully complete clinical trials or obtain marketing approvals for any therapeutic candidates[305]. - The clinical development process is lengthy, complex, and expensive, with no assurance of success[322]. - The company faces significant uncertainties regarding the timing and success of clinical trials, regulatory approvals, and market demand for its therapeutic candidates[304]. - The success of TTX-MC138 is critical, as the company currently has no products approved for commercial sale[315]. - The company must navigate various risks, including competition, regulatory barriers, and the potential for undesirable side effects from its therapeutic candidates[319]. - The results of preclinical studies and early-stage clinical trials may not predict later-stage outcomes, leading to potential setbacks in development[322]. - Successful completion of clinical trials is a prerequisite for submitting marketing applications to the FDA and comparable foreign regulatory authorities[329]. - The company may experience negative or inconclusive results in clinical trials, potentially leading to additional studies or abandonment of product development programs[330]. - The company faces challenges in patient enrollment for clinical trials, which could delay development activities and increase costs[336]. - Quality issues could delay or prevent the delivery of products to clinical trials or the market, impacting regulatory approval[348]. - The company must comply with FDA's good clinical practice and current good manufacturing practice regulations[350]. - The company has received Orphan Drug Designations for TTX-MC138 and TTX-siPDL1 for pancreatic cancer, which may provide market exclusivity benefits[371]. - The FDA may grant Orphan Drug Exclusivity for a product if it is the first to receive approval for a specific disease, preventing other applications for the same indication for seven years[373]. - The company has limited experience in conducting clinical trials necessary for regulatory approvals, which may lead to unpredictable delays[359]. - Regulatory approval processes can vary significantly between the FDA and foreign authorities, potentially impacting the timeline for commercialization[367]. - The FDA's review timelines for New Drug Applications (NDAs) are flexible and can be extended based on workload, which may delay product approvals[364]. - The company may encounter unexpected delays or increased costs due to changes in government regulations or FDA policies during product development[361]. - Regulatory approvals may require costly post-marketing studies and compliance with ongoing requirements[389]. - Failure to comply with regulatory requirements may result in penalties or withdrawal of product approvals[390]. Market and Competitive Landscape - The company faces substantial competition from major biotechnology firms and academic institutions, which may impact its market position[433]. - Mergers and acquisitions in the biopharmaceutical industry could concentrate resources among competitors, increasing competitive pressures[436]. - The company currently lacks a marketing and sales organization, which may hinder its ability to generate product revenue if regulatory approvals are obtained[422]. - Coverage and reimbursement from third-party payors are critical for the commercial success of therapeutic candidates, with significant uncertainty regarding their availability[424]. - The company faces a lengthy sales cycle influenced by market conditions, perceived value of products, and competition, which may adversely affect market acceptance[440]. - The company is dependent on third-party organizations for conducting preclinical studies and clinical trials, which may lead to delays in obtaining regulatory approval[448]. Operational and Organizational Challenges - The company may encounter unforeseen expenses and complications as it transitions from a research-focused entity to one capable of supporting commercial activities[308]. - The company has moved its laboratory operations to new facilities, including a sublease in Newton, Massachusetts, which may affect R&D access[464]. - The company relies heavily on third-party services, and any disruption in these services could delay clinical trials and regulatory approvals[470]. - Failure to effectively expand the organization may hinder the development and commercialization of therapeutic candidates[471]. - Retaining key executives and attracting qualified personnel is critical for success in the competitive oncology industry[472]. - The company faces intense competition for hiring qualified personnel, which may impede research and development objectives[475]. Regulatory and Legislative Environment - Legislative changes, such as the ACA, have significantly impacted the U.S. biotechnology and biopharmaceutical industries, including increased Medicaid rebates and new Medicare discount programs[401]. - The company may experience pricing pressures due to legislative measures aimed at controlling pharmaceutical pricing and reimbursement levels[409]. - The Budget Control Act of 2011 triggered automatic reductions to Medicare payments, which could affect the company's revenue from government programs[403]. - The company is subject to U.S. and foreign trade laws, with violations potentially resulting in substantial fines, penalties, and reputational harm[410]. - Ongoing healthcare reform efforts may materially affect the company's revenue prospects and operational strategies[412]. - The ACA has introduced many programs and requirements that are still not fully understood, posing risks to reimbursement and operational volumes[414]. - The company anticipates that future healthcare reforms may lead to further reductions in Medicare and other healthcare funding, affecting pricing and demand for its products[409]. - The Inflation Reduction Act of 2022 allows CMS to negotiate prices for certain high-cost drugs under Medicare, starting with ten drugs in 2026 and increasing to 20 drugs by 2029[415]. - Medicare beneficiaries' annual out-of-pocket drug expenses are capped at $2,000, which may impact the company's pricing strategies[416]. - The expansion of group purchasing organizations and integrated delivery networks is expected to increase pricing pressure on approved products[420]. Risk Management and Compliance - The company may face substantial liabilities from product liability claims, which could inhibit the commercialization of its therapeutic candidates[357]. - The company may not obtain sufficient product liability insurance, which could further hinder the commercialization of its products[357]. - The company must navigate a complex regulatory landscape, with potential changes in healthcare spending and policies impacting its business[412]. - Compliance with animal welfare regulations could increase operating costs and impact product commercialization[478]. - The ability to utilize net operating loss carryforwards may be limited by ownership changes, potentially affecting future tax liabilities[479].