Lexeo Therapeutics, Inc.

Previous wording

We are a clinical stage genetic medicine company dedicated to reshaping heart health by applying pioneering science to fundamentally change how cardiovascular diseases are treated. We are advancing a portfolio of therapeutic candidates that take aim at the underlying genetic causes of conditions, including FA cardiomyopathy, PKP2 arrhythmogenic cardiomyopathy, and other devastating diseases with high unmet need.

Current wording

We are a clinical stage genetic medicine company dedicated to reshaping heart health by applying pioneering science to fundamentally change how cardiovascular diseases are treated. We are advancing a portfolio of therapeutic candidates that take aim at the underlying genetic causes of conditions, including FA cardiomyopathy, plakophilin-2, or PKP2, arrhythmogenic cardiomyopathy, or ACM, and other devastating diseases with high unmet need.

Previous wording

Our most advanced cardiovascular product candidate, LX2006 for the treatment of FA cardiomyopathy, is currently being evaluated in SUNRISE-FA, our ongoing Phase 1/2 clinical trial and in a Cornell investigator-initiated trial. In July 2024, we provided an interim clinical update, which included baseline characteristics from the 11 treated participants across the two studies and data from the eight participants who had reached at least six-months of follow-up as of that time. These data showed improvements in key cardiac biomarkers including left ventricular mass index, lateral wall thickness, and high-sensitivity troponin I. Additionally, in November 2024 we reported that we observed an increase in frataxin protein expression in the hearts of four patients that had undergone cardiac biopsies (cohort 1 (n=1), cohort 2 (n=3)) as measured by liquid chromatography-mass spectrometry, or LCMS, and immunohistochemistry. LX2006 has been generally well-tolerated across both trials to date. One year after dosing, one participant with multiple comorbidities and a history of flu-like symptoms presented with Grade 2 asymptomatic myocarditis. Six weeks later, a biopsy was negative for myocarditis and the participant remains asymptomatic. In November 2024 we announced alignment with the FDA on key elements of a registrational development plan for LX2006, including an accelerated approval pathway with left ventricular mass index and frataxin protein expression as co-primary registrational endpoints. In February 2025, we reached further alignment with the FDA that the frataxin protein expression co-primary endpoint would be evaluated for any increase from baseline in frataxin positive area as measured by immunohistochemistry as opposed to any specific numerical threshold. In April 2025, we provided an interim clinical update, which included baseline characteristics from the 16 treated participants across the two studies, frataxin protein expression from four additional patients that had undergone cardiac biopsies (cohort 3 (n=4)), and data from the 12 participants who had reached at least six-months of follow-up as of that time. These data showed an increase in frataxin expression versus baseline in all patients that had undergone cardiac biopsies (cohort 1 (n=1), cohort 2 (n=3), cohort 3 (n=4)) as measured by LCMS, upon which we reached further alignment with the FDA to measure protein expression. These data also showed dose responsive increases in frataxin expression relative to dose cohorts, improvements in key cardiac biomarkers including left ventricular mass index, lateral wall thickness, and high-sensitivity troponin I, as well as improvements in functional measures including the Modified Friedreich's Ataxia Rating Scale, or mFARS, and Kansas City Cardiomyopathy Questionnaire, or KCCQ-12.

Current wording

Our most advanced cardiovascular product candidate, LX2006 for the treatment of FA cardiomyopathy, is currently being evaluated in SUNRISE-FA, our ongoing Phase 1/2 clinical trial and in a Cornell investigator-initiated trial. In July 2024, we provided an interim clinical update, which included baseline characteristics from the 11 treated participants across the two studies and data from the eight participants who had reached at least six-months of follow-up as of that time. These data showed improvements in key cardiac biomarkers including left ventricular mass index, lateral wall thickness, and high-sensitivity troponin I. Additionally, in November 2024 we reported that we observed an increase in frataxin protein expression in the hearts of four patients that had undergone cardiac biopsies (cohort 1 (n=1), cohort 2 (n=3)) as measured by liquid chromatography-mass spectrometry, or LCMS, and immunohistochemistry. LX2006 has been generally well-tolerated across both trials to date. One year after dosing, one participant with multiple comorbidities and a history of flu-like symptoms presented with Grade 2 asymptomatic myocarditis. Six weeks later, a biopsy was negative for myocarditis and the participant remains asymptomatic. In November 2024 we announced alignment with the U.S. Food and Drug Administration, or the FDA, on key elements of a registrational development plan for LX2006, including an accelerated approval pathway with left ventricular mass index and frataxin protein expression as co-primary registrational endpoints. In February 2025, we reached further alignment with the FDA that the frataxin protein expression co-primary endpoint would be evaluated for any increase from baseline in frataxin positive area as measured by immunohistochemistry as opposed to any specific numerical threshold. In April 2025, we provided an interim clinical update, which included baseline characteristics from the 16 treated participants across the two studies, frataxin protein expression from four additional patients that had undergone cardiac biopsies (cohort 3 (n=4)), and data from the 12 participants who had reached at least six-months of follow-up as of that time. These data showed an increase in frataxin expression versus baseline in all patients that had undergone cardiac biopsies (cohort 1 (n=1), cohort 2 (n=3), cohort 3 (n=4)) as measured by LCMS, upon which we reached further alignment with the FDA to measure protein expression. These data also showed dose responsive increases in frataxin expression relative to dose cohorts, improvements in key cardiac biomarkers including left ventricular mass index, lateral wall thickness, and high-sensitivity troponin I, as well as improvements in functional measures including the Modified Friedreich's Ataxia Rating Scale, or mFARS, and Kansas City Cardiomyopathy Questionnaire, or KCCQ-12. In July 2025, we received Breakthrough Therapy designation for LX2006 for the treatment of FA cardiomyopathy from the FDA.

Previous wording

Our second most advanced cardiovascular product candidate, LX2020 for the treatment of ACM caused by mutations in the PKP2 gene, referred to as PKP2-ACM, is currently being evaluated in HEROIC-PKP2, an ongoing Phase 1/2 clinical trial. To date, six participants have been enrolled in this trial: three in cohort 1 and three in cohort 2. We have obtained post-treatment cardiac biopsies from two participants in cohort 1; the third cohort 1 participant elected to not undergo the post-treatment biopsy procedure. In these two participants with post-treatment samples, we have observed an increase in PKP2 protein expression in the heart quantified using western blot assay showing a 71% and 115% increase in PKP2 protein expression versus pre-treatment baseline. In addition, the first participant to reach six-months post-treatment experienced a 67% reduction in PVCs from baseline and normalization of QRS duration. Across all participants dosed, LX2020 has been generally well-tolerated with no treatment-related serious adverse events to date. We expect to provide an interim data readout focused on clinical efficacy biomarkers in the second half of 2025.

Current wording

Our second most advanced cardiovascular product candidate, LX2020 for the treatment of ACM caused by mutations in the PKP2 gene, referred to as PKP2-ACM, is currently being evaluated in HEROIC-PKP2, an ongoing Phase 1/2 clinical trial. To date, eight participants have been enrolled in this trial: three in cohort 1, three in cohort 2 and two in cohort 3. We have obtained post-treatment cardiac biopsies from two participants in cohort 1; the third cohort 1 participant elected to not undergo the post-treatment biopsy procedure. In these two participants with post-treatment samples, we have observed an increase in PKP2 protein expression in the heart quantified using western blot assay showing a 71% and 115% increase in PKP2 protein expression versus pre-treatment baseline. In addition, the first participant to reach six-months post-treatment experienced a 67% reduction in premature ventricular contractions from baseline and normalization of QRS duration. Across all participants dosed, LX2020 has been generally well-tolerated with no treatment-related serious adverse events to date. We expect to provide an interim clinical data update in the second half of 2025.

Previous wording

To date, we have funded our operations primarily through proceeds from the sale of shares of our convertible preferred stock and common stock, including our Private Placement, IPO and the subsequent partial exercise of the underwriters’ 30-day option to purchase additional shares of common stock. As of March 31, 2025, we had $106.9 million of cash, cash equivalents, and investments. We have incurred significant operating losses since the commencement of our operations. Our ability to generate product revenue sufficient to achieve profitability will depend heavily on the successful development and eventual commercialization of one or more of our current gene therapy candidates or any future gene therapy candidates. Our net losses for the three months ended March 31, 2025 and the year ended December 31, 2024 were $32.7 million and $98.3 million, respectively, and our accumulated deficit was $312.8 million at March 31, 2025. We expect to continue to incur significant losses for the foreseeable future as we advance our current and future product candidates through preclinical and clinical development, continue to build our operations and operate as a public company.

Current wording

To date, we have funded our operations primarily through proceeds from the sale of shares of our convertible preferred stock, common stock, and pre-funded warrants and warrants to purchase our common stock, including from our May 2025 Private Placement, March 2024 Private Placement, IPO and the subsequent partial exercise of the underwriters’ 30-day option to purchase additional shares of common stock. As of June 30, 2025, we had $152.5 million of cash, cash equivalents, and investments in U.S. Treasury securities. We have incurred significant operating losses since the commencement of our operations. Our ability to generate product revenue sufficient to achieve profitability will depend heavily on the successful development and eventual commercialization of one or more of our current gene therapy candidates or any future gene therapy candidates. Our net losses for the six months ended June 30, 2025 and the year ended December 31, 2024 were $58.8 million and $98.3 million, respectively, and our accumulated deficit was $338.9 million at June 30, 2025. We expect to continue to incur significant losses for the foreseeable future as we advance our current and future product candidates through preclinical and clinical development, continue to build our operations and operate as a public company.

Previous wording

We expect that our general and administrative expenses will decrease in the near to medium term future relative to those incurred during the three months ended March 31, 2025 on a quarterly and annualized basis primarily due to lower anticipated third-party legal fees and related costs, as well as lower anticipated administrative personnel and related costs due to the limited reduction in force undertaken in April 2025, while supporting the continued research and development of our programs and the growth of our business.

Current wording

We expect that our general and administrative expenses will decrease in the near to medium term future relative to those incurred during the three and six months ended June 30, 2025 on a quarterly and annualized basis primarily due to lower anticipated third-party legal fees and related costs, as well as lower anticipated administrative personnel and related costs due to the limited reduction in force undertaken in April 2025, while supporting the continued research and development of our programs and the growth of our business.

Previous wording

Other income (expense), net includes net foreign exchange gains and (losses).

Current wording

Other income (expense), net includes foreign exchange gains and (losses).

Previous wording

We recognized interest income of $1.2 million and $1.7 million for the three months ended March 31, 2025 and March 31, 2024, respectively, primarily related to interest earned on our investments in U.S. government money market funds and our investments in U.S Treasury securities, with the decrease primarily due to lower interest rates, as well as lower invested balances.

Current wording

We recognized interest income of $1.3 million and $2.3 million for the three months ended June 30, 2025 and June 30, 2024, respectively, primarily related to interest earned on our investments in U.S. government money market funds and our investments in U.S Treasury securities, with the decrease primarily due lower average invested balances, as well as lower interest rates.

Previous wording

The net increase of $1.4 million in total research and development expenses for the three months ended March 31, 2025 compared to the three months ended March 31, 2024 was primarily due to increases in (i) employee compensation and stock-based compensation expenses of $1.2 million primarily due to increased headcount and equity awards granted since March 31, 2024, (ii) clinical trial costs of $0.3 million, and (iii) non-clinical and preclinical expenses of $0.2 million primarily related to our cardiovascular disease programs. These increases were partially offset by decreases in (i) chemistry, manufacturing, and control, or CMC, expenses of $0.2 million, and (ii) quality assurance expenses of $0.2 million.

Current wording

The net decrease of $0.4 million in total research and development expenses for the six months ended June 30, 2025 compared to the six months ended June 30, 2024 was primarily due to decreases in (i) CMC expenses of $1.5 million, (ii) clinical trial costs of $0.9 million excluding an adjustment reducing estimated accrued clinical trial expenses by $2.2 million for our LX1001 program recorded in the second quarter of 2024, (iii) license fees of $0.6 million related to the Third Cornell License Agreement, and (iv) non-clinical and preclinical expenses of $0.4 million primarily related to our cardiovascular disease programs. These decreases were partially offset by (i) an adjustment reducing estimated accrued clinical trial expenses by $2.2 million for our LX1001 program recorded in the second quarter of 2024, and (ii) employee compensation and stock-based compensation expenses of $1.0 million primarily due to equity awards granted since June 30, 2024.

Previous wording

The net increase of $9.1 million in general and administrative expenses for the three months ended March 31, 2025 compared to the three months ended March 31, 2024 was primarily due to increases in (i) third-party legal fees and associated costs of $7.5 million, (ii) employee compensation and stock-based compensation expenses of $1.4 million primarily due to increased headcount and equity awards granted since March 31, 2024, and (iii) software, office supplies, and dues and subscription expenses of $0.4 million. These increases were partially offset by a decrease in third-party audit, accounting, investor relations, public relations and other professional service provider fees, as well as insurance expenses, of $0.2 million.

Current wording

The net increase of $18.1 million in general and administrative expenses for the six months ended June 30, 2025 compared to the six months ended June 30, 2024 was primarily due to increases in (i) third-party legal fees and associated costs of $16.2 million, and (ii) employee compensation and stock-based compensation expenses of $2.1 million primarily due to increased headcount and equity awards granted since June 30, 2024. These increases were partially offset by a decrease in investor relations and public relations costs of $0.3 million.

Previous wording

Since our inception, we have not generated any revenue from product sales and have incurred significant operating losses and negative cash flows from our operations. We expect to incur significant expenses and operating losses for the foreseeable future as we advance the clinical development of our product candidates. Since our inception through March 31, 2025, we funded our operations primarily with total net proceeds from sales of our common stock, convertible SAFE Note and convertible equity securities of $377.9 million. As of March 31, 2025 and December 31, 2024, we had cash, cash equivalents, and investments of $106.9 million and $128.5 million, respectively.

Current wording

Since our inception, we have not generated any revenue from product sales and have incurred significant operating losses and negative cash flows from our operations. We expect to incur significant expenses and operating losses for the foreseeable future as we advance the clinical development of our product candidates. Since our inception through June 30, 2025, we funded our operations primarily through proceeds from the sale of shares of our convertible preferred stock, common stock, and pre-funded warrants and warrants to purchase our common stock, including from our May 2025 Private Placement, March 2024 Private Placement, IPO and the subsequent partial exercise of the underwriters’ 30-day option to purchase additional shares of common stock, with net proceeds since our inception totaling $451.0 million. As of June 30, 2025 and December 31, 2024, we had cash, cash equivalents, and investments in U.S. Treasury Securities of $152.5 million and $128.5 million, respectively.

Previous wording

On March 24, 2025 we filed a prospectus supplement to the prospectus which forms a part of our effective shelf registration statement on Form S-3, dated December 13, 2024, which registers the offering, issuance, and sale of up to $75.0 million of common stock pursuant to our ATM Program. As of March 31, 2025, we did not sell any shares of common stock pursuant to the ATM Program.

Current wording

On March 24, 2025 we filed a prospectus supplement to the prospectus which forms a part of our effective shelf registration statement on Form S-3, dated December 13, 2024, which registers the offering, issuance, and sale of up to $75.0 million of common stock pursuant to our ATM Program. As of June 30, 2025, we have not sold any shares of common stock pursuant to the ATM Program.

Previous wording

We believe that our cash, cash equivalents, and investments balances will be sufficient to fund our planned operating expenses and capital expenditure requirements into 2027. Our total future capital requirements will depend on many factors and are subject to the risks and uncertainties set forth in “Item 1A Risk Factors.”

Current wording

We believe that our cash, cash equivalents, and investments in U.S. Treasury securities balances will be sufficient to fund our planned operating expenses and capital expenditure requirements into 2028. Our total future capital requirements will depend on many factors and are subject to the risks and uncertainties set forth in “Item 1A Risk Factors.”

Previous wording

The following table summarizes our sources and uses of cash for the three months ended March 31, 2025 and March 31, 2024 (in thousands):

Current wording

The following table summarizes our sources and uses of cash for the six months ended June 30, 2025 and June 30, 2024 (in thousands):

Previous wording

During the three months ended March 31, 2024, net cash used in operating activities consisted primarily of our net loss of $21.7 million, which was partially offset by $4.0 million of net cash provided by changes in operating assets and liabilities, $2.3 million of stock-based compensation expense and $0.5 million of depreciation and amortization of operating and finance right-of-use assets.

Current wording

During the six months ended June 30, 2025, net cash used in operating activities consisted primarily of our net loss of $58.8 million, which included an unrealized gain of $3.4 million recorded to other non-operating income upon receipt of our long-term investment in convertible preferred stock, and which was partially offset by $6.8 million of stock-based compensation expense, $5.4 million of net cash provided by changes in operating assets and liabilities, and $1.0 million of depreciation and amortization of operating and finance right-of-use assets.

Previous wording

During the three months ended March 31, 2025, net cash used in operating activities consisted primarily of our net loss of $32.7 million, which was partially offset by $6.7 million of net cash provided by changes in operating assets and liabilities, $3.7 million of stock-based compensation expense and $0.5 million of depreciation and amortization of operating and finance right-of-use assets.

Current wording

During the six months ended June 30, 2024, net cash used in operating activities consisted primarily of our net loss of $42.9 million, which was partially offset by $5.2 million of stock-based compensation expense, $1.8 million of net cash provided by changes in operating assets and liabilities, and $1.0 million of depreciation and amortization of operating and finance right-of-use assets.

Previous wording

During the three months ended March 31, 2024, net cash used in investing activities was $0.2 million and consisted of purchases of lab equipment and internal use software.

Current wording

During the six months ended June 30, 2024, net cash used in investing activities was $0.4 million and consisted primarily of purchases of lab equipment.

Previous wording

During the three months ended March 31, 2025, net cash provided by financing activities consisted of proceeds received from the common stock issuances under the 2023 ESPP for $0.2 million, which was partially offset by $0.2 million of principal payments made on equipment finance leases.

Current wording

During the six months ended June 30, 2025, net cash provided by financing activities consisted primarily of the net proceeds received from the May 2025 Private Placement offering of $73.1 million, as well as proceeds received from the common stock issuances under the 2023 ESPP of $0.2 million, which were partially offset by $0.3 million of principal payments made on equipment finance leases.

Previous wording

During the three months ended March 31, 2024, net cash provided by financing activities consisted primarily of the net proceeds received from the Private Placement offering of $88.8 million, which was partially offset by $0.1 million of principal payments made on equipment finance leases.

Current wording

During the six months ended June 30, 2024, net cash provided by financing activities consisted primarily of the net proceeds received from the March 2024 Private Placement offering of $88.7 million, as well as $0.4 million of proceeds received from the exercise of stock options, which were partially offset by $0.2 million of principal payments made on equipment finance leases.