A 6-Month Extension Study to Assess the Long-Term Safety of Engensis in Amyotrophic Lateral Sclerosis

To evaluate the long-term safety of intramuscular injections of Engensis in Participants with Amyotrophic Lateral Sclerosis in more than 2 Participants by System Organ Class and Preferred Term (Safety Analysis Population)

Changes from Baseline (Study VMALS 002-2, Day 0) in Revised Amyotrophic Lateral Sclerosis Function Rating TOTAL scores at Day 365 for Engensis compared to Placebo

There are 12 separate assessments in this neuromuscular assessment covering Bulbar, Fine Motor, Gross Motor and Breathing assessments. Each individual assessment is scored from 0 (worst case) to 4 (best case).

Total score is calculated as the sum of all 12 assessment subscores. Note that only the Total Score will be reported in the clinical study report due to the small number of subjects.

The Total Score range is from a minimum of 0 (worst case) to a maximum of 48 (best case).

As assessed bilaterally by Hand-Held Dynamometry in muscles in the upper and lower extremities. Muscle Strength as Measured by Handheld Dynamometry (lbs.) and Change from Baseline to Day 365 by Muscle Group (ITT Population)

Slow vital capacity is a pulmonary function test that quantifies the volume of air that can be slowly exhaled after slow maximum inhalation. It is measured in Liters of air and the percentage of change from baseline is the Percent Predicted Value and Change from Baseline.

Change from Baseline (Study VMALS 002-2, Day 0) in Slow Vital Capacity on Day 240, Day 300 and Day 365 for Participants with intramuscular administration of Engensis compared to Placebo. Increasing negative Change from Baseline results indicates worsening of respiratory capacity.

Total participants requiring Tracheostomy procedures that received intramuscular administration of Engensis, compared to total Placebo participants requiring Tracheostomy procedures.

Total all-cause Mortality for participants that received intramuscular injections of Engensis, compared to total all-cause Mortality for Placebo participants.

Total participant deaths that received intramuscular administration of Engensis, compared to total Placebo participant deaths.

The Participant completes the 40 questions in the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) with 5 categories: Physical Mobility, Activities of Daily Living and Independence, Eating and Drinking, Communication, and Emotional Reactions. Each question has 5 responses to select from: 0-Never (Best Case), 1-Rarely, 2-Sometime, 3-Often, and 4-Always (Worst Case).

Note for each question there is a Minimum of 0 (Best), to the Maximum 4 (Worst). Decreasing scores indicates improvement of symptoms. The Total Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) scores are per Category as percentages of 100% maximum. Each Category percentage is summed for the Intent-to-treat Population.

The Change from Baseline was calculated and displayed in the Table. ALSAQ-40 was completed at the pre-dose baseline visit (Day 0), and at the Day 240 and Day 365 visits.

The subject's impression of change after treatment was measured with the Patient Global Impression of Change questionnaire through use of the electronic Patient Reported Outcome . This questionnaire measures the subject's perception of how treatment has affected their level of activity, symptoms, emotions, and overall quality of life.

Each descriptor is ranked on an increasing improvement scale; where 1 = No change (or condition has got worse), 2=Almost the same, hardly any change at all, 3=A little better, but no noticeable change, 4=Somewhat better, but the change has not made any real difference, 5=Moderately better, and a slight but noticeable change, 6=Better, and a definite improvement that has made a real and worthwhile difference, and 7 = A great deal better, and a considerable improvement that as made all the difference.

The test was self-administered on Days 240 and 365.

The Clinical Global Impression of Change is a validated instrument completed by observers as an assessment of Quality of Life. The Clinical Global Impression of Change is an 8-point scale with scores ranging rom Marked Improvement, Moderate Improvement, Minimal Improvement, Slight Improvement, and Unchanged (or Worse), along with an efficacy index with questions in a matrix for therapeutic effect and side effects.The test was completed on Days 240 and 365/ Early Termination.