First-in-human study of TN-201, an AAV9 gene replacement therapy in MYBPC3-associated hypertrophic cardiomyopathy: initial safety, pharmacodynamic, and imaging results from MyPEAK-

Milind Y. Desai; Sherif F. Nagueh; John R. Giudicessi; Michael J. Previs; Danielle Kellner; Matthew J. Pollman; Fatbardha Varfaj; Laura A. Robertson; Natasha Sonicheva-Paterson; Richard Pushkin; Brian Mangal; La Tanya Tomlinson; William G. Harrison; Lynn Yamamoto; Gretchen Argast; Laura M. Lombardi; Kathryn N. Ivey; Whittemore G. Tingley

doi:10.1093/cvr/cvaf200

First-in-human study of TN-201, an AAV9 gene replacement therapy in MYBPC3-associated hypertrophic cardiomyopathy: initial safety, pharmacodynamic, and imaging results from MyPEAK-

Milind Y. Desai, Sherif F. Nagueh, John R. Giudicessi, Michael J. Previs, Danielle Kellner, Matthew J. Pollman, Fatbardha Varfaj, Laura A. Robertson, Natasha Sonicheva-Paterson, Richard Pushkin, Brian Mangal, La Tanya Tomlinson, William G. Harrison, Lynn Yamamoto, Gretchen Argast, Laura M. Lombardi, Kathryn N. Ivey, Whittemore G. Tingley

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Abstract

This brief report details the initial findings from a Phase 1b/2 trial of TN-201, an adeno-associated virus serotype 9 (AAV9) gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), a condition with significant morbidity, increased risk of mortality, and no approved therapy for the majority of patients. TN-201 was well tolerated, and changes to the management of potential immune responses resulted in a shorter period of immunosuppression. These results show consistent transduction and expression of TN-201 in cardiomyocytes, corresponding with increases in MyBP-C levels, reductions or stabilization of cardiac biomarkers, and reductions in key measures of left ventricular (LV) hypertrophy.

Original language	English (US)
Pages (from-to)	2628-2631
Number of pages	4
Journal	Cardiovascular Research
Volume	121
Issue number	17
DOIs	https://doi.org/10.1093/cvr/cvaf200
State	Published - Dec 1 2025

ASJC Scopus subject areas

Physiology
Cardiology and Cardiovascular Medicine
Physiology (medical)

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10.1093/cvr/cvaf200

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Desai, M. Y., Nagueh, S. F., Giudicessi, J. R., Previs, M. J., Kellner, D., Pollman, M. J., Varfaj, F., Robertson, L. A., Sonicheva-Paterson, N., Pushkin, R., Mangal, B., Tomlinson, L. T., Harrison, W. G., Yamamoto, L., Argast, G., Lombardi, L. M., Ivey, K. N., & Tingley, W. G. (2025). First-in-human study of TN-201, an AAV9 gene replacement therapy in MYBPC3-associated hypertrophic cardiomyopathy: initial safety, pharmacodynamic, and imaging results from MyPEAK-. Cardiovascular Research, 121(17), 2628-2631. https://doi.org/10.1093/cvr/cvaf200

First-in-human study of TN-201, an AAV9 gene replacement therapy in MYBPC3-associated hypertrophic cardiomyopathy: initial safety, pharmacodynamic, and imaging results from MyPEAK-. / Desai, Milind Y.; Nagueh, Sherif F.; Giudicessi, John R. et al.
In: Cardiovascular Research, Vol. 121, No. 17, 01.12.2025, p. 2628-2631.

Research output: Contribution to journal › Article › peer-review

Desai, MY, Nagueh, SF, Giudicessi, JR, Previs, MJ, Kellner, D, Pollman, MJ, Varfaj, F, Robertson, LA, Sonicheva-Paterson, N, Pushkin, R, Mangal, B, Tomlinson, LT, Harrison, WG, Yamamoto, L, Argast, G, Lombardi, LM, Ivey, KN & Tingley, WG 2025, 'First-in-human study of TN-201, an AAV9 gene replacement therapy in MYBPC3-associated hypertrophic cardiomyopathy: initial safety, pharmacodynamic, and imaging results from MyPEAK-', Cardiovascular Research, vol. 121, no. 17, pp. 2628-2631. https://doi.org/10.1093/cvr/cvaf200

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title = "First-in-human study of TN-201, an AAV9 gene replacement therapy in MYBPC3-associated hypertrophic cardiomyopathy: initial safety, pharmacodynamic, and imaging results from MyPEAK-",

abstract = "This brief report details the initial findings from a Phase 1b/2 trial of TN-201, an adeno-associated virus serotype 9 (AAV9) gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), a condition with significant morbidity, increased risk of mortality, and no approved therapy for the majority of patients. TN-201 was well tolerated, and changes to the management of potential immune responses resulted in a shorter period of immunosuppression. These results show consistent transduction and expression of TN-201 in cardiomyocytes, corresponding with increases in MyBP-C levels, reductions or stabilization of cardiac biomarkers, and reductions in key measures of left ventricular (LV) hypertrophy.",

author = "Desai, \{Milind Y.\} and Nagueh, \{Sherif F.\} and Giudicessi, \{John R.\} and Previs, \{Michael J.\} and Danielle Kellner and Pollman, \{Matthew J.\} and Fatbardha Varfaj and Robertson, \{Laura A.\} and Natasha Sonicheva-Paterson and Richard Pushkin and Brian Mangal and Tomlinson, \{La Tanya\} and Harrison, \{William G.\} and Lynn Yamamoto and Gretchen Argast and Lombardi, \{Laura M.\} and Ivey, \{Kathryn N.\} and Tingley, \{Whittemore G.\}",

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doi = "10.1093/cvr/cvaf200",

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AU - Robertson, Laura A.

AU - Sonicheva-Paterson, Natasha

AU - Pushkin, Richard

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AU - Tingley, Whittemore G.

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First-in-human study of TN-201, an AAV9 gene replacement therapy in MYBPC3-associated hypertrophic cardiomyopathy: initial safety, pharmacodynamic, and imaging results from MyPEAK-

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