On
June 21, 2023, the Company announced promising interim data relating to its ongoing U.S. Phase I/II clinical trial of AMT-130, a
one-time administered investigational gene therapy for Huntington’s disease. The interim data includes up to 24 months of follow-up
data from the 26 patients enrolled in the ongoing U.S. clinical trial. The trial includes a 10-patient low-dose cohort (six treated patients
and four control patients) and a 16-patient high-dose cohort (10 treated patients and six control patients). Patients were randomized
to treatment with AMT-130 or an imitation (sham) surgery. The study consists of a blinded 12-month core study period followed by unblinded
long-term follow-up of five years for treated patients. To date, four of the six control patients in the high-dose cohort have been crossed
over to treatment. Efficacy and biomarker data from the crossover patients were not included in the interim data update.
Safety and Tolerability
AMT-130 was generally well-tolerated with a manageable safety profile
in patients treated with the lower dose of 6x1012 vector genomes and the higher dose of 6x1013 vector genomes. The
most common adverse events in the treatment groups were related to the surgical procedure. No treatment emergent adverse events led to
discontinuation of patient follow-up.
As previously reported, there were two serious adverse events (SAE)
unrelated to AMT-130 (post-operative delirium and major depression) in the low-dose cohort, one SAE in the high-dose cohort (back pain),
and one SAE (deep vein thrombosis) in the control group. In addition, there were two suspected unexpected SAEs (severe headache, central
nervous system inflammation) in the high-dose cohort. All the events have resolved.
All four crossover patients (three high dose, one low dose) received
a short course of immunosuppression therapy concurrent with the administration of AMT-130. Following a review of the interim data analysis,
the Data Safety Monitoring Board for the U.S. Phase I/II clinical trial concluded there are no safety concerns with either dose and recommended
continuing clinical development of AMT-130.
Exploratory Efficacy Data
Clinical and functional measurements for treated patients in each dose
cohort were compared to baseline measurements, control patients (up to 12 months) and a natural history cohort. The natural history cohort
was developed by the Company in collaboration with the Cure Huntington’s Disease Initiative using the TRACK-HD natural history study
of patients with early Huntington’s disease. The natural history cohort includes 31 patients that met the Company’s clinical
trial inclusion-criteria of CAG length, age, Total Functional Capacity, Diagnostic Classification Level and minimum striatal volumes.
| ● | Early clinical data demonstrate trends consistent with a potential clinical benefit of AMT-130 at both doses of AMT-130. |
| ● | Compared to baseline measurements, clinical function was generally preserved at 24 months for patients in the low-dose cohort and
at 12-months for patients in the high-dose cohort. |
| ● | Compared to the natural history, patients in both dose cohorts demonstrated benefits in each of Total Motor Score, Total Functional
Capacity and the composite Unified Huntington’s Disease Rating Scale. |
| o | Total Motor Score (TMS): Low-dose patients demonstrated a mean improvement in TMS of 1.8 points at 24 months compared to the
natural history and high-dose patients demonstrated a mean improvement of 2.7 points at 12 months. |
| o | Total Functional Capacity (TFC): Low-dose patients demonstrated a mean 0.8 point improvement in TFC at 24 months compared to
the natural history and high-dose patients demonstrated a mean 0.5 point improvement at 12 months. |
| o | Composite Unified Huntington’s Disease Rating Scale (cUHDRS): Low-dose patients demonstrated a mean 0.9 point improvement
in cUHDRS at 24 months compared to the natural history and high-dose patients demonstrated a mean 1.0 point improvement at 12 months. |
| ● | Patients
in the control group experienced a worsening of TMS at 12 months compared to baseline measurements and the natural history. TFC and cUHDRS
was preserved in control patients at 12 months. |
Biomarkers
Neurofilament light chain (NfL)
| ● | As expected and as previously reported, patients treated with AMT-130 experienced a transient increase in cerebrospinal fluid (CSF)
NfL related to the procedure that peaked at approximately one month after administration. These transient increases were not dose-dependent
and all patients experienced subsequent declines in CSF NfL. |
| ● | Mean CSF NfL for the low-dose cohort was 12.9% below baseline measurements compared to a predicted 22.9% increase in the natural history,
with four of the five low-dose patients having CSF NfL levels below baseline measurements. |
| ● | CSF NfL levels in the high-dose cohort were more variable through 12 months, with a mean increase of 51.5% compared to baseline. Four
of the eight high-dose patients with at least 12 months of follow up had NfL levels below baseline measurements. Two high-dose patients
with 18 months of follow-up demonstrated a continued decline in CSF NfL to 27.4% above baseline. |
| ● | In
the control group, mean CSF NfL was relatively stable and was 6.83% below baseline measurements at 12-months. |
Mutant Huntingtin protein (mHTT)
| ● | CSF mHTT for the low-dose cohort remained below baseline measurements with a mean reduction of 8.1% at 24 months. CSF mHTT for the
high-dose cohort was significantly more variable with a mean increase of 39.7% above baseline at 12 months compared to a 4.7% increase
in the control group. Three of nine evaluable patients in the high-dose cohort had CSF mHTT reduction below baseline measurements at their
last measurement. |
Total Brain Volume
| ● | The mean total brain volume for the control, low-dose and high-dose cohorts declined 0.74%, 1.02% and 1.23%, respectively at 12 months
and were not significantly different from each other or from the natural history. |
Forward-Looking Statements
This Current Report on Form 8-K contains forward-looking statements
within the meaning of Section 27A of the Securities Act and Section 21E of the Exchange Act. All statements other than statements
of historical fact are forward-looking statements, which are often indicated by terms such as “anticipate,” “believe,”
“could,” “establish,” “estimate,” “expect,” “goal,” “intend,”
“look forward to,” “may,” “plan,” “potential,” “predict,” “project,”
“seek,” “should,” “will,” “would” and similar expressions and the negatives of those terms.
Forward-looking statements are based on management’s beliefs and assumptions and on information available to management only as
of the date of this Current Report on Form 8-K. These forward-looking statements include, but are not limited to, the potential clinical
and functional effects of AMT-130. The Company’s actual results could differ materially from those anticipated in these forward-looking
statements for many reasons, including risks related to conducting the clinical trial for Huntington’s disease, the impact of financial
and geopolitical events on the Company and the wider economy and health care system, the Company’s clinical development activities,
clinical results, collaboration arrangements, regulatory oversight, product commercialization and intellectual property claims, as well
as the risks, uncertainties and other factors described under the heading “Risk Factors” in the Company’s periodic securities
filings, including its Annual Report on Form 10-K filed with the Securities and Exchange Commission on February 27, 2023 and
its Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 9, 2023. Given these risks, uncertainties
and other factors, you should not place undue reliance on these forward-looking statements, and the Company assumes no obligation to update
these forward-looking statements, even if new information becomes available in the future.