Lexeo Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Operational Highlights

Rhea-AI Summary

Lexeo Therapeutics (NASDAQ: LXEO) has reported its Q4 and full-year 2024 financial results, highlighting significant progress in its gene therapy programs. The company achieved further FDA alignment on LX2006's pivotal study for Friedreich ataxia cardiomyopathy, with protein expression to be evaluated for any increase from baseline.

Early data from the LX2020 HEROIC-PKP2 Phase 1/2 trial showed promising results, with 71% and 115% increases in PKP2 protein expression in the first two post-treatment biopsies. The first participant demonstrated a 67% reduction in premature ventricular contractions after 6 months.

Financial highlights include:

• Cash position of $128.5 million, providing runway into 2027
• Q4 2024 R&D expenses of $18.4 million vs $8.2 million in Q4 2023
• Q4 2024 net loss of $25.9 million ($0.78 per share)
• Full-year 2024 net loss of $98.3 million ($3.09 per share)

Positive

• Promising early efficacy data with 71-115% protein expression increases in LX2020 trial
• Strong cash position of $128.5M providing runway into 2027
• FDA alignment achieved for LX2006 pivotal study pathway
• European orphan drug designation received for LX2020
• Favorable safety profile with no treatment-related serious adverse events

Negative

• Net loss increased to $98.3M in 2024 from $66.4M in 2023
• R&D expenses increased 39.5% year-over-year to $74.1M
• G&A expenses doubled to $31.7M in 2024 from $15.4M in 2023

Insights

Biotechnology Financial Analyst

Lexeo's Q4 and 2024 financial results reveal a dual narrative of increasing R&D investment alongside strategic regulatory progress. The company's cash position of $128.5 million providing runway into 2027 represents a significant operational cushion as they advance their gene therapy programs through clinical development.

Annual R&D expenses increased 39.5% to $74.1 million, reflecting the company's commitment to advancing their clinical pipeline. G&A expenses also rose substantially to $31.7 million, a 105.8% increase year-over-year. While the net loss expanded to $98.3 million, the extended cash runway indicates efficient capital allocation despite increased spending.

The regulatory alignment with FDA on LX2006's development pathway represents material risk reduction for this program. The modified endpoint for frataxin expression evaluation - requiring any increase from baseline rather than a specific threshold - potentially streamlines the path to market. This flexibility in protein expression targets, combined with the inclusion of pediatric cohorts and use of natural history controls, could accelerate development timelines and reduce trial costs.

For LX2020, the early protein expression data and functional improvements in the first cohort, combined with completed enrollment in cohort 2, establish important clinical proof-of-concept milestones. The orphan designation in Europe adds another layer of regulatory advantage and potential market exclusivity.

The current financial position supports continued development through several value-creating clinical milestones expected in 2025, including additional LX2006 data and LX2020 cohort 2 results, without immediate financing pressure.

Clinical Development Expert

Lexeo's clinical updates for both lead programs demonstrate meaningful progression in addressing significant unmet needs in rare cardiovascular genetic disorders.

For the LX2006 Friedreich ataxia program, the regulatory alignment represents a critical development. The FDA's acceptance of any increase in frataxin expression from baseline as a co-primary endpoint, rather than requiring a pre-defined threshold, acknowledges the biological complexity of gene replacement therapy. This is particularly significant given the correlation observed between frataxin expression and improvements in left ventricular mass index (LVMI) in patients with abnormal baseline LVMI.

The inclusion of pediatric cohorts in the planned pivotal study is equally important, as earlier intervention in progressive genetic disorders typically yields better outcomes. The use of prospective natural history data as an external control is consistent with FDA's flexibility for rare disease development and eliminates the ethical concerns of placebo-controlled trials in severe progressive disorders.

For the LX2020 PKP2-ACM program, the interim data shows promising biological activity. The 71% and 115% increases in PKP2 protein expression from post-treatment biopsies provide direct evidence of successful gene transfer and expression. More compelling is the 67% reduction in premature ventricular contractions in the first patient evaluated at 6 months, suggesting functional cardiac improvements beyond just protein expression.

The favorable safety profile reported for both programs is reassuring, as AAV-based gene therapies can sometimes trigger immune responses. The completion of enrollment in cohort 2 for LX2020 sets up important data readouts for the second half of 2025 that could further validate this approach for arrhythmogenic cardiomyopathy.

Additional alignment with FDA on LX2006 planned pivotal study including protein expression co-primary endpoint: based on improvements in LVMI across participants with abnormal LVMI at baseline, frataxin expression to be evaluated for any increase from baseline rather than numerical threshold

Interim update from cohort 1 of LX2020 HEROIC-PKP2 Phase 1/2 trial: observed 71% and 115% increases in PKP2 protein expression in first two post-treatment biopsies; first participant evaluated 6-months after dosing experienced 67% reduction in premature ventricular contractions (PVCs)

Completed enrollment of cohort 2 of LX2020 HEROIC-PKP2 Phase 1/2 trial; interim clinical data update expected in second half of 2025

LX2020 has been generally well tolerated with no treatment-related serious adverse events to date

Cash, cash equivalents and investments of $128.5 million expected to provide operational runway into 2027

NEW YORK, March 24, 2025 (GLOBE NEWSWIRE) -- Lexeo Therapeutics, Inc. (Nasdaq: LXEO), a clinical stage genetic medicine company dedicated to pioneering novel treatments for cardiovascular diseases, today provided business updates across its portfolio and reported fourth quarter and full year 2024 financial results.

“We are pleased to share further regulatory clarity for LX2006 for the treatment of Friedreich ataxia (FA) cardiomyopathy, and we appreciate the continued partnership from the FDA on an accelerated approval pathway to support adults and children living with this devastating condition,” said R. Nolan Townsend, Chief Executive Officer of Lexeo Therapeutics. “We are also encouraged by the favorable safety profile and early data observed in participants dosed with LX2020 to date. We look forward to sharing additional clinical updates later in 2025 now that the second cohort of the LX2020 HEROIC-PKP2 Phase 1/2 trial in arrhythmogenic cardiomyopathy is fully enrolled.”

Business and Program Updates
LX2006 for the Treatment of FA Cardiomyopathy:

• Regulatory Update: Further alignment on elements of the accelerated development pathway following a Type B RMAT meeting with the U.S. Food and Drug Administration (FDA):
  • Frataxin expression to be evaluated for any increase from baseline rather than numerical threshold, based on improvements to date in LVMI across participants with abnormal LVMI at baseline
  • Inclusion of pediatric cohorts, both adolescents and children, in planned pivotal study
  • Use of prospective natural history data as external control in planned pivotal study
  • Final dose selection and remaining elements of registrational trial alignment expected in 2025
    

In light of these regulatory updates and anticipated timelines for assay validation, the Company expects to measure frataxin protein expression using liquid chromatography mass spectrometry (LCMS) in the planned registrational trial.

• Mid-Year Clinical Update Expected to Include:
  • Safety and tolerability data for all participants dosed across both the SUNRISE-FA and Weill Cornell clinical trials (at least 16 participants, including 6 participants with abnormal LVMI at baseline)
  • Pre- and post-treatment cardiac frataxin protein expression measured via LCMS for all four participants at the highest dose (1.2x10¹² vg/kg, Cohort 3)
  • Clinical biomarker data, including left ventricular mass index (LVMI), left ventricular wall thickness and high-sensitivity troponin I, for participants with >6-months of follow up
  • Functional and patient-reported outcome data for participants with >6-months of follow up
• Safety: LX2006 continues to be generally well tolerated with no new treatment-related serious adverse events to report

LX2020 for the Treatment of PKP2-ACM:

• Cohort 1 Interim Update: Post-treatment cardiac biopsies from two participants in cohort 1 showed increases in PKP2 protein expression from baseline; the third cohort 1 participant elected not to undergo a post-treatment biopsy
  • Observed increases in exogenous mRNA and 71% and 115% increases in PKP2 protein levels from baseline
  • First participant evaluated 6-months post treatment experienced 67% reduction in PVCs from baseline (from 861 to 284) and resolution of non-specific intraventricular block (normalization of QRS duration)
• Enrollment Update: Completed enrollment of cohort 2 of LX2020 HEROIC-PKP2 (n=3), interim clinical data update expected in second half of 2025
• Safety: LX2020 has been generally well tolerated with no treatment-related serious adverse events to date across both dose cohorts
• Regulatory Update: In March 2025 the European Commission granted orphan medicinal product designation for LX2020 for the treatment of PKP2-ACM

Fourth Quarter and Full Year Financial Results

• Cash Position: As of December 31, 2024, cash, cash equivalents, and investments were $128.5 million, which Lexeo believes will be sufficient to fund operations into 2027.
• R&D Expenses: R&D expenses were $18.4 million for the three months ended December 31, 2024, compared to $8.2 million for the three months ended December 31, 2023. R&D expenses were $74.1 million for the year ended December 31, 2024, compared to $53.1 million for the year ended December 31, 2023.
• G&A Expenses: G&A expenses were $9.0 million for the three months ended December 31, 2024, compared to $6.8 million for the three months ended December 31, 2023. G&A expenses were $31.7 million for the year ended December 31, 2024, compared to $15.4 million for the year ended December 31, 2023.
• Net Loss: Net loss was $25.9 million or $0.78 per share (basic and diluted) for the three months ended December 31, 2024, compared to $14.2 million or $0.86 per share (basic and diluted) for the three months ended December 31, 2023. Net loss was $98.3 million or $3.09 per share (basic and diluted) for the year ended December 31, 2024, compared to $66.4 million or $12.40 per share (basic and diluted) for the year ended December 31, 2023.

About Lexeo Therapeutics
Lexeo Therapeutics is a New York City-based, clinical stage genetic medicine company dedicated to reshaping heart health by applying pioneering science to fundamentally change how cardiovascular diseases are treated. The Company is advancing a portfolio of therapeutic candidates that take aim at the underlying genetic causes of conditions, including LX2006 for the treatment of Friedreich ataxia (FA) cardiomyopathy, LX2020 for the treatment of plakophilin-2 (PKP2) arrhythmogenic cardiomyopathy, and other devastating diseases with high unmet need.

Cautionary Note Regarding Forward-Looking Statements
Certain statements in this press release may constitute “forward-looking statements” within the meaning of the federal securities laws, including, but not limited to, Lexeo’s expectations and plans regarding its current product candidates and programs and the timing for receipt and announcement of data from its clinical trials, the timing and likelihood of potential regulatory approval, and expectations regarding the time period over which Lexeo’s capital resources will be sufficient to fund its anticipated operations and estimates regarding Lexeo’s financial condition. Words such as “may,” “might,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “design,” “estimate,” “predict,” “potential,” “develop,” “plan” or the negative of these terms, and similar expressions, or statements regarding intent, belief, or current expectations, are forward-looking statements. While Lexeo believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements. These forward-looking statements are based upon current information available to the company as well as certain estimates and assumptions and are subject to various risks and uncertainties (including, without limitation, those set forth in Lexeo’s filings with the U.S. Securities and Exchange Commission (SEC)), many of which are beyond the company’s control and subject to change. Actual results could be materially different from those indicated by such forward-looking statements as a result of many factors, including but not limited to: risks and uncertainties related to global macroeconomic conditions and related volatility; expectations regarding the initiation, progress, and expected results of Lexeo’s preclinical studies, clinical trials and research and development programs; the unpredictable relationship between preclinical study results and clinical study results; delays in submission of regulatory filings or failure to receive regulatory approval; liquidity and capital resources; and other risks and uncertainties identified in Lexeo’s Annual Report on Form 10-K for the annual period ended December 31, 2023, filed with the SEC on March 11, 2024, Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2024, filed with the SEC on November 13, 2024, and subsequent future filings Lexeo may make with the SEC. Additional information will also be set forth in Lexeo’s Annual Report on Form 10-K for the year ended December 31, 2024. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Lexeo claims the protection of the Safe Harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. Lexeo expressly disclaims any obligation to update or alter any statements whether as a result of new information, future events or otherwise, except as required by law.

Media Response:
Media@lexeotx.com

Investor Response:
Carlo Tanzi, Ph.D.
ctanzi@kendallir.com

Lexeo Therapeutics, Inc.
Selected Financial Information
(in thousands, except share and per share amounts)

Statements of Operations

	Three Months Ended December 31,								Year Ended December 31,
	2024				2023				2024				2023
	(unaudited)				(unaudited)
Operating expenses
Research and development	$	18,366			$	8,210			$	74,091			$	53,130
General and administrative		9,016				6,764				31,675				15,383
Total operating expenses		27,382				14,974				105,766				68,513
Operating loss		(27,382	)			(14,974	)			(105,766	)			(68,513	)
Other income and expense
Loss on fair value adjustment to convertible SAFE Note		-				(258	)			-				(530	)
Other income (expense), net		-				(8	)			(9	)			(13	)
Interest expense		(30	)			(51	)			(137	)			(205	)
Interest income		1,465				1,103				7,556				2,867
Accretion of discount on investments		23				-				23				-
Total other income and expense		1,458				786				7,433				2,119
Loss from operations before income taxes		(25,924	)			(14,188	)			(98,333	)			(66,394	)
Income taxes		-				-				-				-
Net loss	$	(25,924	)		$	(14,188	)		$	(98,333	)		$	(66,394	)
Net loss per common share, basic and diluted	$	(0.78	)		$	(0.86	)		$	(3.09	)		$	(12.40	)
Weighted average number of shares outstanding used in computation of net loss per common share, basic and diluted		33,076,094				16,438,237				31,787,491				5,354,368

Balance Sheet Data

		December 31,				December 31,
		2024				2023
Cash, cash equivalents, and investments		$	128,530			$	121,466
Total assets			146,942				139,807
Total liabilities			30,100				26,272
Total stockholders' equity			116,842				113,535

FAQ

What are the key results from Lexeo's LX2020 HEROIC-PKP2 Phase 1/2 trial in 2024?

The trial showed 71% and 115% increases in PKP2 protein expression in first two post-treatment biopsies, with one participant showing 67% reduction in PVCs after 6 months. The treatment has been well-tolerated with no serious adverse events.

How long will LXEO's current cash position sustain operations?

Lexeo's cash position of $128.5 million is expected to fund operations into 2027.

What is the status of LXEO's LX2006 program for Friedreich ataxia cardiomyopathy?

FDA provided alignment on pivotal study, including protein expression evaluation from baseline and inclusion of pediatric cohorts. Final dose selection and trial alignment expected in 2025.

How did LXEO's R&D expenses change in Q4 2024 compared to Q4 2023?

R&D expenses increased to $18.4 million in Q4 2024 from $8.2 million in Q4 2023.

What regulatory milestone did LXEO's LX2020 achieve in Europe?

In March 2025, LX2020 received orphan medicinal product designation from the European Commission for PKP2-ACM treatment.