Key Takeaways LYRA shares jumped 355.5% this week after LYR-210 met the goal in the phase III ENLIGHTEN 2 CRS study. LYR-210 showed strong symptom relief and improved SNOT-22 scores at 24 weeks, starting as early as week 4. Lyra plans to discuss ENLIGHTEN 2 data with the FDA and may seek approval for LYR-210 in CRS without polyps.Shares of Lyra Therapeutics (LYRA) have skyrocketed 355.5% in a week after the company announced encouraging results from the late-stage study on its lead candidate, LYR-210, whi ...

ENLIGHTEN 2 Study Results ENLIGHTEN 2: A Phase III, Randomized, Blinded, Controlled, Parallel-Group Trial to Evaluate the Efficacy and Safety of LYR-210 for the Treatment of Chronic Rhinosinusitis (CRS) in Adults https://clinicaltrials.gov/study/NCT05295459 June 2, 2025 FLS Disclaimer This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The words "believe," "may," "will," "estimate," "continue," "anticipate," "intend," "expect," an ...

Core Insights - Lyra Therapeutics' shares experienced a significant surge of 550% in pre-market trading following positive results from its drug trials [1] - The stock price increased from $4.93 to over $32, despite being down more than 50% year-to-date [1] Drug Trial Results - The drug candidate LYR-210 showed statistically significant results in treating chronic rhinosinusitis (CRS) in adults [3] - The ENLIGHTEN 2 trial met its primary endpoint, showing marked improvement in three core CRS symptoms: nasal obstruction, discharge, and facial pain at 24 weeks [4] - Key secondary endpoints were also achieved, with a 22.4-point reduction in the SNOT-22 score, indicating a significant improvement in symptom severity [5] - LYR-210 was well-tolerated, with a safety profile comparable to the control group [5] Regulatory Plans - The company plans to align with the FDA for a New Drug Application (NDA) submission for patients without nasal polyps [6] Financial Performance - In Q1 2025, Lyra reported revenue of $0.18 million, missing consensus estimates by nearly 24% [7] - This revenue figure is a decline from $0.53 million in the same quarter last year, and the company has only beaten revenue expectations once in the past four quarters [8] Market Sentiment - Despite the positive trial results and stock surge, Wall Street analysts remain cautious, with all three covering analysts maintaining a 'Hold' rating and a 12-month price target of $2.00, indicating a potential 59% downside from Friday's close [8]

Summary of Lyra Therapeutics Conference Call on ENLIGHTEN Two Phase Three Trial Results Company Overview - **Company**: Lyra Therapeutics (LYRA) - **Focus**: Development of LYR210 for the treatment of chronic rhinosinusitis (CRS) Industry Context - **Industry**: Biopharmaceuticals, specifically targeting chronic rhinosinusitis - **Market Opportunity**: Approximately 8 million patients treated annually in the US, with 50% failing current therapies, representing a significant market opportunity of around $60 billion in annual healthcare expenditures related to CRS [7][6] Core Findings from the ENLIGHTEN Two Trial - **Positive Results**: The ENLIGHTEN Two trial demonstrated statistically significant improvements in the primary endpoint (change from baseline in the three cardinal symptoms or 3CS) and key secondary endpoints (SNOT22 score) at 24 weeks [20][21] - **Patient Demographics**: The trial included approximately 180 CRS patients who had failed medical management, with 55% from North America and 45% from Europe [12] - **Safety Profile**: The trial reported a favorable safety profile with no serious adverse events related to the product or procedure [13][21] Detailed Trial Results - **Primary Endpoint**: At week 24, LYR210 showed a 1.13 improvement over sham control in 3CS, with a p-value of 0.00078 [14] - **Key Secondary Endpoints**: - SNOT22 score improvement of 8.7 over sham, with a p-value of 0.0101, exceeding the minimal clinically important difference of 8.9 points [16] - Numerical improvement in percent ethmoid opacification by CT, showing a 2.2 point improvement over sham [17] - **Subgroup Analysis**: Consistent positive trends were observed in patients with grade one nasal polyps, mirroring results in non-polyp patients [19] Future Plans and Regulatory Strategy - **FDA Engagement**: Lyra plans to meet with the FDA in the second half of 2025 to discuss the regulatory strategy for LYR210, including potential NDA submissions [21][35] - **Next Steps**: Initiation of a Phase III trial for patients with nasal polyps is planned for the first half of 2026, pending additional financing [21] - **Funding Needs**: Estimated cost for a potential new trial (ENLIGHTEN Three) is around $20 million, with current cash reserves of $32 million expected to last until early next year [46] Additional Insights - **Comparison with Previous Trials**: Differences in results between ENLIGHTEN One and Two were attributed to variations in patient populations and site characteristics, with a noted higher sham effect in US patients during ENLIGHTEN One [27][28] - **Market Strategy**: The company aims to leverage existing data on approved steroid treatments to support its NDA filing, emphasizing the strong safety and efficacy profile of LYR210 [41][42] Conclusion - **Overall Sentiment**: The results from the ENLIGHTEN Two trial are viewed positively, reinforcing the potential of LYR210 as a new standard of care for CRS patients who have not responded to existing treatments [21][20]

Core Insights - Lyra Therapeutics announced positive results from the ENLIGHTEN 2 Phase 3 clinical trial of LYR-210 for chronic rhinosinusitis (CRS), achieving its primary endpoint with significant symptom improvement compared to sham control [1][4][5] Clinical Trial Results - The ENLIGHTEN 2 trial met its primary endpoint, showing a statistically significant improvement in the composite of the three cardinal symptoms (3CS) of CRS at week 24 (-1.13; p=0.0078) in patients without nasal polyps [1][5] - Key secondary endpoints were also met, including a significant improvement in 3CS at 24 weeks in the full population (-0.90; p=0.0209) and in the SNOT-22 score (-8.7; p=0.0101) [2][4] - Symptom improvement was observed as early as week 4, with sustained improvements throughout the trial [2][5] Safety and Tolerability - LYR-210 was well-tolerated, with a safety profile similar to sham control and no product-related serious adverse events reported [6] - Commonly reported adverse events included epistaxis, upper respiratory tract infection, and headache [6] Future Development Plans - The company plans to review the total dataset from the ENLIGHTEN trials to evaluate next steps for pursuing an indication in non-polyp patients and to continue development in patients with nasal polyps [4][7] - Lyra aims to align with the FDA for a New Drug Application (NDA) submission for patients without nasal polyps [7] Market Potential - LYR-210 is designed to provide six months of continuous anti-inflammatory therapy with a single administration, targeting the estimated four million CRS patients in the U.S. who fail medical management each year [12]

Core Viewpoint - Lyra Therapeutics is set to present 52-week results from the ENLIGHTEN 1 Phase 3 study for LYR-210, a treatment for chronic rhinosinusitis (CRS), at the COSM 2025 conference [1][2] Group 1: Product Overview - LYR-210 is a bioabsorbable nasal implant designed to deliver six months of continuous anti-inflammatory therapy using mometasone furoate for CRS patients who have failed current therapies [3][4] - The ENLIGHTEN program includes two pivotal Phase 3 clinical trials, ENLIGHTEN 1 and ENLIGHTEN 2, with approximately 180 CRS patients enrolled in each trial [2][4] Group 2: Clinical Trial Results - Results from the ENLIGHTEN 1 Phase 3 Extension Stage indicate a favorable safety profile for LYR-210, consistent with the Primary Study Phase [5][6] - In the subgroup of CRS patients with nasal polyps, improvements were observed in both symptoms and polyp size among those who crossed over from the sham group to receive LYR-210 [5][6] Group 3: Upcoming Events - The poster presentation for LYR-210 is scheduled for May 16 and 17, 2025, at the COSM 2025 conference in New Orleans [6]

Company Performance - Lyra Therapeutics reported a quarterly loss of $0.12 per share, better than the Zacks Consensus Estimate of a loss of $0.15, and an improvement from a loss of $0.35 per share a year ago, representing an earnings surprise of 20% [1] - The company posted revenues of $0.18 million for the quarter ended March 2025, missing the Zacks Consensus Estimate by 23.75%, and a decline from year-ago revenues of $0.53 million [2] - Over the last four quarters, the company has surpassed consensus EPS estimates three times, but has topped consensus revenue estimates only once [2] Stock Performance - Lyra Therapeutics shares have declined approximately 49.7% since the beginning of the year, compared to a decline of 3.9% for the S&P 500 [3] - The current consensus EPS estimate for the upcoming quarter is -$0.17 on revenues of $0.24 million, and for the current fiscal year, it is -$0.61 on revenues of $0.97 million [7] Industry Outlook - The Medical - Drugs industry, to which Lyra Therapeutics belongs, is currently ranked in the top 22% of over 250 Zacks industries, indicating a favorable outlook compared to the bottom 50% [8] - The performance of Lyra Therapeutics may be influenced by the overall industry outlook, as empirical research shows a strong correlation between near-term stock movements and trends in earnings estimate revisions [5][8]

Financial Performance - As of March 31, 2025, total assets decreased to $56,316,000 from $66,346,000 as of December 31, 2024, representing a decline of approximately 15%[20] - Collaboration revenue for the three months ended March 31, 2025, was $183,000, down 65% from $532,000 in the same period of 2024[22] - Total operating expenses for Q1 2025 were $9,024,000, a decrease of 62% compared to $24,056,000 in Q1 2024[22] - The net loss for Q1 2025 was $8,547,000, compared to a net loss of $22,452,000 in Q1 2024, indicating a reduction of approximately 62%[22] - Cash and cash equivalents at the end of Q1 2025 were $31,735,000, down from $40,577,000 at the end of 2024, reflecting a decrease of about 22%[20] - The accumulated deficit increased to $413,337,000 as of March 31, 2025, from $404,790,000 at the end of 2024[20] - The Company recorded a restructuring charge of $10.9 million in 2024 and an additional $0.9 million in Q1 2025, primarily related to severance and retention costs[35] - The Company has reported basic net loss per share attributable to common stockholders, reflecting ongoing financial challenges since inception[48] - The Company may need additional financing to support future operations and growth strategies, as it has incurred recurring net operating losses[42] - The Company has incurred net losses of $413.3 million since inception, with cash and cash equivalents of approximately $31.7 million as of March 31, 2025, raising doubts about its ability to continue as a going concern[133] Workforce and Restructuring - Following the failure of the ENLIGHTEN 1 trial, the company reduced its workforce by 87 employees and halted commercialization efforts for LYR-210[33] - The Company has a restructuring liability balance of $4.039 million as of March 31, 2025, which includes severance and retention costs[55] - The Company engaged a valuation specialist to determine the fair value of right-of-use assets using a discount rate of 9.5-10.5%[61] - The company has initiated a strategic review, leading to a workforce reduction of approximately 75% in May 2024[162] - A reduction in force was approved by the Board, affecting up to 87 employees, with charges of approximately $11.8 million incurred for severance and related costs[216] Research and Development - The Company plans to report results from the ongoing Phase 3 ENLIGHTEN 2 trial for LYR-210 in the second quarter of 2025[122] - LYR-210 showed a mean improvement in the 3CS score of 3.21 points in CRS patients with nasal polyps, compared to 0.96 points in sham control, achieving statistical significance (p-value 0.0058)[129] - The Company has paused development efforts for LYR-220 as part of cost-saving measures announced in May 2024[128] - The company expects to incur significant commercialization expenses related to product sales, marketing, manufacturing, and distribution if marketing approval is obtained for any product candidates[188] - The costs to advance product candidates to marketing approval are expected to be substantial, particularly for the LYR-210 product candidate[217] Financing and Capital Requirements - The Company raised an aggregate of $424.8 million since inception, primarily from equity securities[39] - The Company plans to seek stockholder approval for a reverse stock split to regain compliance with Nasdaq's minimum bid price requirement[38] - The Company has $50.2 million available for future sale under the Amended Sales Agreement as of March 31, 2025[73] - The company plans to fund operations through public or private equity or debt financings, as it does not expect to generate significant revenue from product sales in the foreseeable future[135] - Future capital requirements will depend on costs related to clinical trials, manufacturing, and commercialization activities for product candidates[191] Lease and Operating Costs - The Company executed the Waltham Lease in May 2022, comprising approximately 29,000 square feet with an initial base rent of $2.2 million per year, increasing by 3% annually until June 30, 2033[106] - The Waltham Sublease was executed in December 2023, covering approximately 24,000 square feet with a base rent of $1.8 million per year, also increasing by 3% annually until November 30, 2032[108] - Total lease costs for the three months ended March 31, 2025, were $1.895 million, down from $2.531 million for the same period in 2024, reflecting a decrease of approximately 25%[110] - The Company's operating lease liabilities as of March 31, 2025, totaled $41.355 million, with a present value of $33.356 million after accounting for imputed interest[113] - The operating lease for office and laboratory space in Watertown has a base rent of $2.0 million per year, expiring in April 2027[210] Collaboration and Revenue Generation - The company has not generated revenue from product sales and recognized $4.9 million in collaboration revenue from the LianBio License Agreement as of March 31, 2025[147] - Under the LianBio License Agreement, the company received an upfront payment of $12.0 million and is eligible for up to $135.0 million in future milestone payments[150] - Deferred revenue related to the Combined Performance Obligation was $11,748,000 as of March 31, 2025, with no revenue recognized during the three months ended March 31, 2025[99] - LianBio's collaboration revenue decreased from $532,000 in Q1 2024 to $183,000 in Q1 2025, a decline of 65.5%[173] Future Outlook and Strategic Options - The company is exploring operational and strategic options, including additional clinical trials and potential asset sales, following the failure of the ENLIGHTEN 1 trial[146] - The company anticipates that its cash, cash equivalents, and short-term investment balance will be sufficient to fund operating expenses into the first quarter of 2026[189] - The company may need to relinquish rights to technologies or future revenue streams if it raises additional funds through collaborations or licensing arrangements[140] - Future acquisitions or partnerships may dilute stockholder value and incur additional debt or liabilities[214] - The timing and size of future acquisitions or partnerships remain unpredictable and could impact operating results[214]

Financial Performance - Cash and cash equivalents as of March 31, 2025, were $31.7 million, down from $40.6 million at December 31, 2024[8] - Research and development expenses for Q1 2025 were $4.9 million, a decrease of 73% compared to $18.2 million for the same period in 2024[9] - General and administrative expenses for Q1 2025 were $3.3 million, down from $5.8 million in Q1 2024, reflecting a reduction in professional and consulting fees[10] - Net loss for Q1 2025 was $8.5 million, significantly reduced from $22.5 million in Q1 2024[11] - Total operating expenses for Q1 2025 were $9.0 million, compared to $24.1 million for the same period in 2024[12] Clinical Trials - The ENLIGHTEN 2 pivotal Phase 3 trial results for LYR-210 in CRS are expected in Q2 2025[7] - The ENLIGHTEN program includes two pivotal Phase 3 trials, with approximately 180 CRS patients enrolled in each trial[5] Strategic Plans - The company plans to implement a reverse stock split to comply with Nasdaq's minimum bid price requirement[6] - The company anticipates that its cash balance will fund operations into Q1 2026[8] Product Information - LYR-210 is designed to deliver six months of continuous anti-inflammatory therapy for CRS patients[15]

Clinical Trials and Development - The Phase 3 ENLIGHTEN 1 trial for LYR-210 did not meet its primary endpoint, showing a mean improvement in the 3CS score of 2.13 points compared to 2.06 points in sham control at 24 weeks, which was not statistically significant[21] - The ENLIGHTEN 2 trial for LYR-210 is ongoing, with topline results expected in Q2 2025, which will inform the future development path for LYR-210[22] - In the ENLIGHTEN 1 trial, LYR-210 showed a mean improvement in the SNOT-22 score of 20.2 points compared to 15.70 points in sham control[24] - The 52-week extension stage of the ENLIGHTEN 1 trial was completed in Q4 2024, showing consistent safety data with no product-related serious adverse events[26] - LYR-210 is designed to provide six months of continuous anti-inflammatory treatment with a single administration, targeting CRS patients who have failed previous medical management[34] - In the Phase 1 trial, LYR-210 achieved a significant improvement in SNOT-22 scores, with an average change from baseline of -20.5 points at week 24 (p < 0.0001)[44] - The Phase 2 trial (LANTERN) showed that at the 7,500 µg dose, LYR-210 achieved a statistically significant improvement in SNOT-22 scores, with a change from baseline of -19.0 points at week 24 (p=0.001)[44] - The Phase 3 trial (ENLIGHTEN 1) did not meet its primary endpoint, showing a mean improvement in the 3CS score of 2.13 points compared to 2.06 points in sham control[46] - The Phase 3 trial (ENLIGHTEN 2) is ongoing, with topline results expected in Q2 2025[49] - LYR-210 was generally well tolerated, with no product-related serious adverse events reported in both the treatment and extension phases[48] - The Phase 2 trial was impacted by COVID-19, leading to enrollment discontinuation at 67 patients[44] - Treatment with LYR-210 resulted in a statistically significant improvement in the 3CS score of 3.21 points compared to 0.96 points in sham control, with a difference of 2.25 points (p-value 0.0058) in CRS patients with nasal polyps[51] - In patients with a nasal congestion score of 2 or greater, LYR-210 showed an LS mean improvement of 3.69 points compared to 0.75 points in sham control, resulting in a difference of 2.94 points (p-value 0.0017)[51] - The Phase 2 LANTERN clinical trial enrolled 67 patients due to COVID-19, falling short of the planned 99 evaluable patients[52] - At the 7,500 µg dose, LYR-210 achieved significant improvements in 4CSS at weeks 16 (-1.47, p=0.021), 20 (-1.61, p=0.012), and 24 (-1.64, p=0.016), but did not meet the primary endpoint at week 4[56] - Approximately 50% of patients experienced a durable response post-removal of LYR-210, with no worsening of 4CSS from the Week 24 baseline[58] - The clinical development process is long and uncertain, with significant risks of failure at any stage, impacting the company's ability to commercialize its product candidates[186] - Delays in clinical trials may arise from various factors, including regulatory disagreements, recruitment challenges, and unforeseen safety issues, potentially increasing costs and delaying marketing approval[189] - The company has transitioned most of its clinical manufacturing to an in-house facility but is no longer engaged in manufacturing its product candidates as of May 2024[193][194] - The company has suspended its manufacturing activities, which may affect its ability to meet clinical and regulatory timelines[195] - If LYR-210 fails to demonstrate safety and efficacy, the company may face significant setbacks in its development plans and revenue generation[199] - The company has not conducted head-to-head trials comparing LYR-210 to other treatments, which could impact its market acceptance if LYR-210 is not shown to be more effective[202] - The company may incur unplanned costs and face delays in obtaining marketing approval for its product candidates due to various unforeseen events during clinical trials[188] - Regulatory authorities may impose modifications or suspensions on clinical trials, which could further delay the development of LYR-210[190] - The company has limited influence over the performance of third-party contractors involved in clinical trials, which may lead to compliance issues and delays[190] - The company is currently seeking feedback from regulatory authorities, which may not be provided in a timely manner, potentially impacting development timelines[190] - The company intends to seek FDA approval for LYR-210 through the Section 505(b)(2) regulatory pathway, which could potentially expedite the development program by relying on existing data[206] - If the FDA does not allow the use of the Section 505(b)(2) pathway, the company may face significantly longer approval times and increased costs, potentially delaying market entry[206] - The pharmaceutical industry is highly competitive, and patent litigation could delay NDA approvals for up to 30 months or longer[207] - Clinical trials for LYR-210 are being conducted outside the United States, primarily in Europe, but the FDA may not accept data from these trials, which could necessitate additional costly trials[209] - LYR-210 will be regulated as a drug-device combination product, which may complicate the approval process and increase the time and resources required for market entry[211] - The company has not obtained regulatory approval for any product candidates, and the lengthy approval process may hinder commercialization efforts[217] - Approval processes vary among countries, and failure to comply with international regulatory requirements could limit market potential[216] - The company must demonstrate substantial evidence from well-controlled clinical trials to satisfy regulatory agencies, which may require additional studies and resources[218] - Only a small percentage of products in development successfully complete the regulatory approval process, posing a significant risk to the company's business prospects[219] - Delays in obtaining regulatory approvals may diminish competitive advantages and hinder the ability to generate revenue from product candidates[214] Financial and Operational Impact - Following the trial results, the company reduced its workforce by approximately 75%, impacting 87 employees, and paused development efforts for LYR-220[21] - The company estimates that approximately 14 million people in the U.S. are affected by CRS, with about 4 million failing medical management annually[31] - LYR-210 aims to address the needs of up to 4 million CRS patients in the U.S. who fail current medical management[38] - The company is evaluating strategic options to maximize shareholder value, with no assurance that any transaction will be completed[34] - LYR-220 development has been paused as part of cost-saving measures, following positive topline results from the Phase 2 BEACON trial[27] - The company plans to build a targeted in-house sales force to engage ENT physicians, who perform 80% of CRS procedural volume, for the commercialization of LYR-210[75] - A holistic reimbursement strategy will be executed to ensure market access, focusing on educating payors about the clinical and pharmacoeconomic attributes of LYR-210[76] - The company entered into a License and Collaboration Agreement with LianBio for the development and commercialization of LYR-210, receiving an upfront payment of $12.0 million and potential future payments of up to $135.0 million based on milestone achievements[78] - The company is entitled to receive low double-digit royalties on net sales of LYR-210 in the licensed territories, while LianBio is responsible for clinical development and commercialization in those regions[79] - The company faces significant competition from larger pharmaceutical and biotechnology firms, which may have greater financial resources and established market presence[82] - The company has 27 issued U.S. patents and 41 foreign issued patents as of December 31, 2024, with additional pending applications[88] - The first lineage of patents provides protection potentially until 2030, while the fourth lineage, filed in 2021, could extend protection until 2042[89] - The company relies on single source suppliers for key components, which may impact its ability to supply products and develop candidates[85] - The company incurred operating losses of approximately $93.4 million and $62.7 million for the years ended December 31, 2024 and 2023 respectively[149] - The company has no approved products and has generated no product revenues to date[164] - The company executed a sublease agreement for approximately 24,000 square feet at a base rent of $1.8 million per year, increasing 3% annually until November 30, 2032[146] - The company expects to incur significant additional operating losses for the foreseeable future and may never achieve profitability[151] - The company has suspended further development of LYR-220 and will require substantial additional funds to develop and commercialize LYR-210[158][165] - The company incurred charges of approximately $10.9 million related to a reduction in force affecting up to 87 employees[150] - The company maintains cash and cash equivalents in accounts exceeding insured limits, which could be impacted by market conditions[160] - The company may need to raise additional capital through equity offerings or debt financings, which could dilute existing shareholders[162][163] - The company is responsible for real estate taxes, maintenance, and other operating expenses under its leases, which could impact financial condition if subleasing is unsuccessful[147] - The company is exploring strategic alternatives following the failure to meet the primary endpoint of the ENLIGHTEN 1 Phase 3 clinical trial announced in May 2024[141] - The company has three leaseholds in Massachusetts representing significant operating costs and is attempting to sublease or assign these leaseholds[143] - Third-party payors are increasingly reducing reimbursements for pharmaceutical products and services, impacting sales potential[130] - The IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare beginning in 2026[134] - The distribution of prescription pharmaceutical products is subject to the Prescription Drug Marketing Act, which regulates drug distribution at the federal level[127] - The company may incur significant costs related to the evaluation of strategic options, including legal and advisory fees[142] - The FDA imposes strict regulations on marketing, labeling, and promotion of pharmaceutical products, with potential consequences for non-compliance[125] Regulatory Environment - The regulatory approval process for LYR-210 involves multiple stages, including preclinical studies, IND submission, and clinical trials, requiring substantial time and financial resources[92] - The company is subject to extensive FDA regulations, and failure to comply may result in sanctions that could adversely affect its operations[92] - The FDA has a goal of 10 months to review and act on a standard NDA and 6 months for a priority NDA, measured from the filing date[100] - The FDA may require submission of a risk evaluation and mitigation strategy (REMS) plan to ensure that the benefits of the drug outweigh its risks[102] - The FDA conducts a preliminary review of all NDAs within the first 60 days after submission to determine completeness for substantive review[103] - The FDA may refer an application for a novel drug to an advisory committee for independent expert evaluation and recommendations[104] - The FDA generally accepts data from foreign clinical trials in support of an NDA if conducted under an IND and in accordance with GCP requirements[106] - The Hatch-Waxman Amendments allow for a Section 505(b)(2) NDA, which can rely on existing studies not conducted by the applicant[110] - The FDA may grant Fast Track Designation for drugs intended to treat serious conditions and demonstrating potential to address unmet medical needs[115] - Priority review designation can reduce the FDA review period to 6 months for drugs offering major advances in treatment[116] - Accelerated approval may be granted based on surrogate endpoints that predict clinical benefit, with post-marketing studies required[117] - Breakthrough therapy designation expedites the development and review of drugs showing substantial improvement over existing therapies[119] - The FDA may require post-marketing testing, including Phase 4 clinical trials, to monitor product safety and effectiveness after commercialization[122]