- Completion of treatment and 6 months follow-up for the last patient enrolled in Stage 1 of the adaptative clinical trial P1-GM-101
- DSMB recommends study continuation as scheduled after review of safety data for the 5 subjects treated with LYS-GM101, paving the way for Stage 2 initiation
- Positive biomarker data demonstrating sustained biological activity of LYS-GM101
Paris, France — 29 November 2022 at 06:00 pm CET — Lysogene (FR0013233475 – LYS), a phase 3 gene therapy platform Company targeting central nervous system (CNS) diseases, today announces that the independent Data Safety Monitoring Board (DSMB) has completed its review of the safety data from Stage 1 of the adaptative clinical trial with investigational gene therapy LYS-GM101, an AAVrh10 vector carrying the human beta-galactosidase (β-gal) coding sequence, for the treatment of GM1 gangliosidosis and recommended continuation of the study as planned.
After favorable safety data from the ongoing adaptative clinical trial P1-GM-101 with LYS-GM101 for the treatment of GM1 gangliosidosis (NCT04273269) in the first two patients with late infantile GM1 gangliosidosis (LI), the Company enrolled earlier this year three subjects with early infantile GM1 gangliosidosis (EI) to complete the first in human Stage 1 part of the study. No adverse events linked to the intra-cisternal route of administration, nor the investigational gene therapy were observed at 3 months post-dosing, with 2 subjects followed up beyond 12 months.
Analysis of β-gal enzyme activity in the cerebrospinal fluid (CSF) of 4 subjects dosed with LYS-GM101 showed increases from baseline levels in all patients. In one LI subject, β-gal activity increased by 11 pmol/ml/h at 6 months after dosing with LYS-GM101, representing a 1.5-fold increase above baseline. In the second LI subject, β-gal activity increased by 44 and 33 pmol/ml/h at 6 and 12 months after dosing, respectively, representing 2.5- and 2.1-fold increases above baseline, respectively. In two EI subjects, β-gal activity increased by 14 at 3 months and 13 pmol/ml/h at 6 months post-dosing, representing 2.1- and 2.8-fold increases above baseline levels, respectively.
Increases in β-gal activity were accompanied by decreases in concentrations of the β-gal substrate GM1 ganglioside in the CSF of the treated patients. In one LI subject, GM1 ganglioside concentrations at 6 months post-dosing with LYS-GM101 decreased by 62% relative to baseline levels. In the second LI subject, GM1 ganglioside concentrations decreased by 28% and 64% at 6 and 12 months after dosing, respectively. In two EI subjects, GM1 ganglioside concentrations decreased by 34% at 3 months and 42% at 6 months post-dosing, respectively.
These results demonstrate that treatment with LYS-GM101 led to sustained expression and functional activity of the transgene product β-gal in all analyzed patients of the P1-GM-101 trial.
Stage 2 of the adaptative clinical trial with LYS-GM101 will consist of a confirmatory efficacy phase with the enrolment of 12 patients that will start soon after the interim analysis for the Stage 1 portion of the study has been completed.
In order to continue the development of LYS-GM101 in accordance with the requirements of regulatory agencies, the Company will need to secure an adequate cash runway. In this regard, the Company continues to pursue strategic discussions with a priority for a non-dilutive solution in the form of a licensing collaboration for one or more of its programs. In the meantime, the Company maintains its cost control initiatives initiated at the beginning of the year. It is reminded that the Company’s current cash runway extends to February 2023.
Dr Marie Trad, M.D., Chief Medical Officer of Lysogene, said: “We are very encouraged with the positive DSMB review, which confirms that our gene therapy and the route of administration have been well tolerated by the patients. In addition, we are pleased to see significant changes in beta-galactosidase and GM1 ganglioside levels in the cerebrospinal fluid. The biomarker data provide evidence for sustained expression and biological activity of the transgene product delivered by LYS-GM101. These results mark an important milestone for the development of LYS-GM101 and pave the way for the initiation of the confirmatory efficacy phase of our trial”.
Lysogene is a gene therapy Company focused on the treatment of orphan diseases of the central nervous system (CNS). The Company has built a unique capability to enable delivery of gene therapies to the CNS to treat lysosomal diseases and other disorders of the CNS. A phase 2/3 clinical trial in MPS IIIA is ongoing. An adaptive clinical trial in GM1 gangliosidosis is also ongoing. Lysogene is also developing an innovative AAV gene therapy approach for the treatment of Fragile X syndrome, a genetic disease related to autism. The Company also entered into an exclusive worldwide license agreement with Yeda, the commercial arm of the Weizmann Institute of Science, for a novel gene therapy candidate for Parkinson disease with GBA1 mutations. www.lysogene.com.
Forward Looking Statement
This press release may contain certain forward-looking statements, especially on the Company’s progress of its clinical trials and cash runway. Although the Company believes its expectations are based on reasonable assumptions, all statements other than statements of historical fact included in this press release about future events are subject to (i) change without notice, (ii) factors beyond the Company’s control, (iii) clinical trial results, (iv) increased manufacturing costs, (v) potential claims on its products. These statements may include, without limitation, any statements preceded by, followed by or including words such as “target,” “believe,” “expect,” “aim,” “intend,” “may,” “anticipate,” “estimate,” “plan,” “objective”, “project,” “will,” “can have,” “likely,” “should,” “would,” “could” and other words and terms of similar meaning or the negative thereof. Forward-looking statements are subject to inherent risks and uncertainties beyond the Company’s control that could cause the Company’s actual results, performance or achievements to be materially different from the expected results, performance or achievements expressed or implied by such forward-looking statements. A further list and description of these risks, uncertainties and other risks can be found in the Company’s regulatory filings with the French Autorité des Marchés Financiers, including in the 2021 universal registration document, registered with the French Markets Authorities on April 19, 2022, and future filings and reports by the Company. Furthermore, these forward-looking statements are only as of the date of this press release. Readers are cautioned not to place undue reliance on these forward-looking statements. Except as required by law, the Company assumes no obligation to update these forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. If the Company updates one or more forward-looking statements, no inference should be drawn that it will or will not make additional updates with respect to those or other forward-looking statements.
This press release has been prepared in both French and English. In the event of any differences between the two texts, the French language version shall supersede.
Côme de La Tour du Pin
Chief Financial Officer ad interim
+ 33 1 41 43 03 90
Contacts – Patients