The Prospective Study for Symptomatic Relief of Essential Tremor with Cala Therapy (PROSPECT) trial is registered with clinicaltrials.gov under identifier NCT03597100. This study was supported by Cala Health, Inc.

Clinical Trial Information*

These results suggest non-invasive transcutaneous a�erent patterned stimulation over a three-month period results in safe and e�ective reduction in hand tremor for essential tremor patients.

Conclusions

Patient survey results indicated 85% of patients found the device convenient and easy to use. 64% of patients reported persistent tremor relief lasting on average 96.7 ± 12 minutes (mean ± SEM) a�er a stimulation session. Device-related adverse events occurred in 18% of patients, with no reported device-related serious adverse events.

Device Usability & Safety

The median improvement ratio (pre-stimulation ÷ post-stimulation tremor power), was computed over all at-home stimulation sessions for each patient. Therapeutic e�icacy varied across the population, but 92% of patients showed improvement in tremor power and 54% showed at least a 2-fold improvement in tremor power.

Patient

128

8

1

64

32

1 50 100 17515025 75 125Trem

or P

ower

Impr

ovem

ent R

atio 92% of patients showed improvement (> 0% reduction)

54% of patients had ≥ 50% reduction (improvement ratio ≥ 2)

25% of patients had ≥ 70% reduction (improvement ratio ≥ 3.3)16

4

2

1⁄21⁄4

Per-Patient Tremor Power Reduction Over All Therapy Sessions

The device’s onboard accelerometers measured postural hold tremor power before and immediately a�er stimulation for each at-home therapy session. Analysis of simultaneously-recorded postural hold TETRAS rating and tremor power at clinic visit 1 confirmed these measures were correlated (r = 0.66, p < 0.0001) and that tremor power could be used as a valid remote measurement of therapeutic e�icacy. In total, 193 patients completed 21,806 home therapy sessions over the 90-day trial.

Secondary Kinematic Endpoint: Tremor Power

Example:Tremor MotionMeasurements

Pre Post

Acce

lera

tion

(m/s

2 )

0 2-4

-2

2

0

Example session where tremor power, computed from the illustrated motion data, decreased from 18 (m/s2)2 to 2 (m/s2)2, i.e. improvement ratio = 9.

1Time (s)

...

TETRAS

Visit 1 Pre Visit 3 PostBain & Findley ADL

Visit 1 Pre Visit 3 PostSevere6.8%

Moderate58.0%

Mild35.1%

Severe2.0%

Moderate21.0%

Mild77.1%

Moderate45.4%

Mild50.2%

Severe3.9%

Slight0.5%

Mild62.4%

Slight16.6%

Severe0.5%

Moderate20.5%

0 - 6 7 - 12 13 - 18 19 - 24Slight Mild Moderate Severe

8 - 16 17 - 24 25 - 32Mild Moderate Severe

Total summed TETRAS score (from 6 tasks) Total summed ADL score (from 8 tasks)

Severity Classification Changes

Patients’ total dominant hand TETRAS and Bain & Findley ADL ratings were classified as either Slight (corresponding to an average rating across tasks of 0 - 1), Mild (>1 - 2), Moderate (>2 - 3), or Severe (>3 - 4). Average rating is total rating divided by 6 (TETRAS) or 8 (Bain & Findley ADL). Tremor severity improved with therapy: 62% (on TETRAS) and 68% (on Bain & Findley ADL) of patients who were rated as Moderate or Severe at baseline improved to Slight or Mild post-stimulation at the final clinic visit.

TETRAS (le�) and Bain & Findley ADL (right) dominant hand score improved before and a�er the therapy session conducted at each visit (n = 205, p < 0.0001). Post-stimulation tremor ratings a�er three months of therapy were significantly better than baseline pre-stimulation tremor ratings (p < 0.0001). In all plots, error bars represent ±1 standard error of the mean, and * indicates p < 0.0001.

TETRAS (Physician-Rated)24

18

12

6

0

Visit 1Pre

12.69.8

11.99.7

11.8 9.8

PostVisit 2

Pre PostVisit 3

Pre Post

*** *

Bain & Findley ADL (Patient-Rated)32

24

16

8Visit 1

Pre

18.414.5

16.413.7 15.8 13.4

PostVisit 2

Pre PostVisit 3

Pre PostDom

inan

t Han

d Sc

ore

Dom

inan

t Han

d Sc

ore

** * *

Co-primary Co-primary

Pre- and Post-Stimulation Per Clinic Visit

Tremor severity was quantified using the physician-rated Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) and patient-rated Bain & Findley Activities of Daily Living (ADL) Scale before and a�er stimulation at each clinic visit. Co-primary clinical endpoints were TETRAS and Bain & Findley ADL score changes from baseline (pre-stimulation, Visit 1) to study conclusion (post-stimulation, Visit 3).

Primary Clinical Endpoints: Tremor Ratings

The patient’s tremor frequency was captured from a 20 second postural hold. The peak tremor frequency was determined onboard the device and used to determine a patient-specific stimulation pattern.

The device consisted of a stimulator and detachable band containing two working electrodes positioned over the median and radial nerves, and a counter-electrode positioned on the dorsal surface of the wrist.

Device, Base Station & Electrode Placement Device Calibration Postures

20 Seconds

Lateral Postural Hold Forward Postural Hold

Device Design and Patient-Specific Calibration

Patient population and study timeline. This was a prospective, multi-center, single-arm, three month study with 263 ET patients (age 69.6 ± 10.1 (23-89) years (mean ± SD; range); ET onset age 43.9 ± 20.4 (2-79) years) enrolled across 26 sites. Patients were seen for three in-clinic visits for study inclusion screening and to establish tremor baseline (Visit 1), and for one-month (Visit 2) and three-month (Visit 3) follow-ups. Following screening, patients were fitted with the TAPS device on the dominant hand. The stimulation frequency was calibrated to each patient’s tremor frequency, and stimulation amplitude was increased to each patient’s comfort level. Following device calibration and initial evaluation of therapy e�icacy, patients were instructed to use the device on their dominant hand at home for 40-minute stimulation sessions twice-daily. 205 patients completed their third in-clinic visit and were included in the primary clinical endpoint analyses. 193 of the 205 patients had valid at-home session data and were included in the secondary kinematic analyses.

V ISIT 1Screening & Enrollment

• Device calibration• TETRAS, ADL ratings

VISIT 2Month 1 Follow-Up

• TETRAS, ADL ratings

VISIT 3Month 3 Follow-Up

• TETRAS, ADL ratings• Patient survey on quality of life changeHOME USE • 2 stimulation sessions per day

• Kinematics before and a�er each session

Clinic Visits and Home Use of Device

ObjectiveThis study evaluated the safety and e�icacy of daily use of a wrist-worn neuromodulation device delivering non-invasive transcutaneous a�erent patterned stimulation (TAPS) therapy for symptomatic relief from hand tremor in adults with essential tremor (ET) over a three month at-home trial, with sparse in-clinic visits.

Stuart Isaacson, MD1, Elizabeth Peckham, DO2, Olga Waln, MD3, Christopher Way, DO4, Nabila Dahodwala, MD, MSc5, Winona Tse, MD6, Melita Petrossian, MD7,Mark Lew, MD8, Cameron Dietiker, MD9, Nijee Luthra, MD9, Michael Soileau, MD10, Rajesh Pahwa, MD11 on behalf of trial investigators

1Parkinson’s Disease and Movement Disorders of Boca Raton, Boca Raton, FL, 2Central Texas Neurology Consultants, Round Rock, TX, 3Houston Methodist Neurological Institute, Houston, TX, 4Parkinson’s Institute and Clinical Center, Mountain View, CA,5University of Pennsylvania, Philadelphia, PA, 6Mount Sinai School of Medicine, New York, NY, 7Pacific Neuroscience Institute, Santa Monica, CA, 8University of Southern California, Los Angeles, CA, 9University of California San Francisco, San Francisco, CA,

10Texas Movement Disorders Specialists, PLLC, Georgetown, TX, 11 University of Kansas Medical Center, Kansas City, KS

Non-Invasive, At-Home Use Neuromodulation Device Provides Symptomatic ReliefFrom Essential Tremor: Results From The PROSPECT* Study