Non-Invasive, At-Home Use Neuromodulation Device

Provides Symptomatic Relief From Essential Tremor

*Clinical trial information: The Prospective Study for Symptomatic Relief of Essential Tremor with Cala Therapy (PROSPECT) trial was registered with clinicaltrials.gov under identifier NCT03597100.

Author disclosures:

This study was funded by Cala Health, Inc. Drs. Pahwa and Isaacson serve as clinical advisors for Cala Health.

Dr. Pahwa received consulting fees from Abbott, AbbVie, ACADIA, Acorda, Adamas, Cala Health, Global Kinetics, Impel Neuropharma, Lundbeck, Neurocrine, Orbis Bioscience, PhotoPharmics, Prilenia, Sunovion, Teva Neuroscience, US World Meds. He also received research support from Abbott, AbbVie, Acorda, Biogen, Boston Scientific, Cala Health, Cavion, Cynapsus, Intec, Kyowa, Lilly, NIH/NINDS, NPF, PSG, Roche, Sunovion, Theranexus, Theravance, US WorldMedsVoyager.

Rajesh Pahwa, MD1, Elizabeth Peckham, DO2, Winona Tse, MD3,Olga Waln, MD4, Christopher Way, DO5, Melita Petrossian, MD6,

Nabila Dahodwala, MD, MSc7, Michael Soileau, MD8, Mark Lew, MD9, Cameron Dietiker, MD10, Nijee Luthra, MD10, Stuart Isaacson, MD11

on behalf of PROSPECT* trial investigators

1University of Kansas Medical Center, Kansas City, KS2Central Texas Neurology Consultants, Round Rock, TX

3Mount Sinai School of Medicine, New York, NY4Houston Methodist Neurological Institute, Houston, TX

5Parkinson’s Institute and Clinical Center, Mountain View, CA6Pacific Neuroscience Institute, Santa Monica, CA

7University of Pennsylvania, Philadelphia, PA8Texas Movement Disorders Specialists, PLLC, Georgetown, TX

9University of Southern California, Los Angeles, CA10University of California San Francisco, San Francisco, CA

11Parkinson’s Disease and Movement Disorders of Boca Raton, Boca Raton, FL

Essential tremor affects over 7 million adults in the US and impairs ability to perform activities of daily living.

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Current treatment options are ineffective or inaccessible for many patients.

Pharmacotherapy(e.g., propranolol, primidone)

Non-medical Options(e.g., assistive devices)

Neurosurgical Options(e.g., deep brain surgery, thalamotomy)

Individualized transcutaneous afferent patterned stimulation (TAPS) of peripheral nerves may desynchronize tremulous neural activity in VIM and reduce tremor symptoms.

• Patterned stimulation desynchronizes tremulous activity in the brain1,2

• Stimulation of median and radial nerves activates distinct subpopulations within VIM3,4

• This interrupts the tremulous activity and reduces hand tremor

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1. Tass, PA. Prog. Theor. Phys. Suppl. 20032. Tass PA. Biol. Cybern. 20033. Houze B, et al. Human brain mapping 2011.4. Baumgartner C, et al. Encephalography and clinical

neurophysicilogy 1993.5. Lin PT et al. Mov Disorder 20186. Pahwa R et al. Neuromodulation 2019.

Stimulation period individualized to tremor frequency

Median Stimulation WaveformRadial Stimulation Waveform

Synchronized firing in median

distribution

Out-of-phase synchronization in radial distribution

Two randomized controlled trials have shown Transcutaneous Afferent Patterned Stimulation (TAPS) to be safe and effective in treatment of ET compared to sham in single use in-clinic setting 5, 6

Study design

Device description, calibration

Study endpoints

Co-primary clinician and patient-rated endpoints, change from baseline (pre-stim, Visit 1) to study exit (post-stim, Visit 3)

- TETRAS subset score relevant to the stimulated upper limb

- Bain & Findley ADL subset score relevant to the stimulated upper limb

Secondary device-measured endpoint, evaluated at home over three months

- Improvements in tremor power from pre- to post-stimulation

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We conducted a multicenter 3-month open label study (PROSPECT) to evaluate the safety and efficacy of TAPS therapy over 3 months of home use.

TETRAS: The Essential Tremor Rating Assessment Scale; BF-ADL: Bain & Findley Activities of Daily Living Scale;QUEST: Quality of Life in Essential Tremor Questionnaire; C/PGI: Clinician/Patient Global Impression of Improvement

TETRAS and BF-ADL scores improved at study exit.

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• Patients improved in TETRAS & BF-ADL from baseline (pre Visit 1) to study completion (post Visit 3)

• Patients improved in TETRAS & BF-ADL within each in-clinic visit

• For each of the rated subtasks, 58 - 80% of patients with tremor in that subtask improved.

* P << 0.0001

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Tremor severity improved for most patients, with over 60% of severe or moderate patients improving to mild or better.

• 62% of patients with ‘severe’ or ‘moderate’ TETRAS scores improved to ‘mild’, ‘slight’, or ‘none’.

• 68% of patients with ‘severe’ or ‘moderate’ ADL scores improved to ‘mild’ or ‘none’.

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Tremor power showed significant improvement across 21,806stimulation sessions

Tremor power is calculated from the wrist acceleration data and captures tremor amplitude and frequency. Tremor power decreases with lower amplitude motions and lower frequency motions.

Tremor power was measured for all at-home sessions and was found to decreased with stimulation.

Tremor power was validated as a measure of tremor severity in-clinic against gold-standard TETRAS ratings.

Almost all patients had improved tremor power at home, and over half of the patients had at least a 50% reduction in tremor.

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The improvement ratio is defined as the pre-stimulation tremor power divided by post-stimulation tremor power. An improvement ratio > 1 indicates reduction in tremor power; = 1 indicates no

change in tremor power; and < 1 indicates worsening in tremor power.

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Device-related adverse events (AEs)• There were no device-related serious AEs.• Non-serious AEs occurred in 18% of patients (primarily skin irritation, sore/lesions,

discomfort or burns that resolved without medical intervention).• All AEs resolved either without intervention, with decreasing stimulation level,

with topical ointment, or discontinuing therapy until resolved

Patient-reported ease of use• 85% of patients reported the device was convenient and easy to use.• 64% patients reported symptomatic tremor relief from therapy that persisted 96

± 12 (mean ± 1 standard error) after the end of stimulation.

The device had a favorable safety profile and was rated easy to use.

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• This three-month home-use clinical trials demonstrated that TAPS therapy provided therapeutic benefit with favorable safety profile over 3 months of home use.

• Response to therapy was reproduced across clinician-rated scores, patient-rated scores, and objective accelerometer measures.

• Tremor reduction is comparable to first-line pharmacotherapies: propranolol and primidone, but without their side effect profile 1-2

• Some patients had tremor reduction as large as 55-90%, similar to surgical outcomes, but without the risk of permanent side effects 1,3

• Increased objectivity and frequency of at-home accelerometer-based metrics demonstrate how wearable tech can measure efficacy over longitudinal use in real world evidence studies

Key takeaways and future plans

1 Zesiewicz T a, Elble R, Louis ED, et al. Practice parameter: therapies for essential tremor: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2005;64:2008–2020. 10.1212/01.WNL.0000163769.28552.CD.

2 Hedera P, Cibulčík F, Davis TL. Pharmacotherapy of Essential Tremor. J Cent Nerv Syst Dis. SAGE Publications; 2013;5:JCNSD.S6561.3 Sinai A, Nassar M, Eran A, et al. Magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: a 5-year single-center experience. J Neurosurg. Epub 2019 Jul 5.:1–8. 10.3171/2019.3.JNS19466.