PWSAI Family Conference - WordPress.com · – Drugs that effect weight loss or any study endpoints...

PWSAI Family ConferenceOctober 5, 2019

| © 2019 Soleno Therapeutics

Soleno Therapeutics• Biotech company based in Redwood City, California • Focused on the development of therapies for rare

diseases • Recently opened EU HQ, Soleno Therapeutics Europe

Ltd., in Dublin • Lead program is DCCR for the treatment of Prader Willi

Syndrome • Currently conducting a Phase III study in the US and UK

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DCCR Efficacy and Safety Trial IN Young children and adults with PWS


DCCR - How does it work?• Appetite is controlled by a region of the brain called the

hypothalamus – NPY/AgRP neurons – which increase appetite – POMC neurons – which decrease appetite

• The function of neurons involved in stimulating appetite is increased in PWS, driving hyperphagia

• DCCR appears to open certain channels in these neurons thereby reducing appetite and hyperphagia – The channels are also expressed on other parts of the body such as fat

cells, liver, pancreas, etc., which can lead to other benefits in PWS

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| Confidential

Diazoxide Choline Controlled-Release (DCCR)

• A once daily tablet formulation of diazoxide choline, which breaks down into diazoxide – Diazoxide has a long history of safe use - FDA approved in 1976

• Previously administered IV for high blood pressure • Prescribed 2-3 times per day as an oral suspension for treatment of low

blood sugar due to increased insulin levels in infants, children and adults • DCCR has advantages over diazoxide that make it suitable

for use in PWS • DCCR has extensive pre-clinical and clinical data

supporting its safety

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| Confidential

Why we believe DCCR may work

• A previous pilot study in overweight or obese PWS patients aged 10 - 22 showed a significant:

– improvement in hyperphagia – improvement in lean muscle mass – decrease in body fat mass – reduction in waist circumference – reduction in aggressive behaviors

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DCCR Program Design

• Patients will be randomized in a 2:1 ratio to DCCR or placebo • All patients successfully completing C601 are eligible to enroll in C602

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3 months placebo-controlled treatment 12-month open-label safety study

C601 ~100 patients at ~20

US sites

C602

• C601 (DESTINY PWS): Multi-center, randomized, double-blind, placebo-controlled, parallel arm study in patients with PWS (Phase III)

• C602: Open-label safety extension study


Study Objectives• Primary objective

• To evaluate the effects of DCCR compared to placebo on hyperphagia in PWS patients • Secondary objectives

• To evaluate changes in body fat mass, Clinical Global Impression of Improvement (CGI-I), and Caregiver Global Impression of Change (GI-C)

• Additional objectives • To evaluate the safety of DCCR in PWS patients • To evaluate changes in other body composition parameters, BMI, waist circumference,

lipid parameters, patient’s health-related quality of life, caregiver burden, cardiometabolic markers, Clinical Global Impression of Severity, Caregiver Global Impression of Severity, and PWS behaviors

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Study Objectives

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• Primary objective is to evaluate the effects of DCCR compared to placebo on hyperphagia in PWS patients

Endpoint: o Hyperphagia change from Baseline to Visit 7

• Secondary objectives are to evaluate changes in body fat mass, Clinical Global Impression of Improvement (CGI-I), and Caregiver Global Impression of Change (GI-C) Endpoints:

o Body fat mass (DXA) change from Baseline to Visit 7 o Clinical Global Impression of Improvement at Visit 7 o Caregiver Global Impression of Change at Visit 7


Key Inclusion Criteria

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In order to be eligible for enrollment, subject must:

• Provide written informed consent • Be 4 years of age and older • Have genetically-confirmed Prader-Willi syndrome and be hyperphagic • Be in a stable care setting for at least 6 months prior to Visit 1 • Be on stable regimens of medications for at least 3 months prior to the

Visit 1


Key Exclusion Criteria

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In order to be eligible for enrollment, subject must not: • Weigh < 20 kg or ≥ 135 kg • Have participated in another interventional clinical study within 60 days prior to Visit 1 • Have any history of allergic reaction to diazoxide, thiazides, sulfonamides • Have a history of blood clots • Have Type I diabetes • Have uncontrolled hypertension • Be pregnant or breastfeeding • Use of any of the prohibited medications within 3 months of Visit 1

– Drugs that effect weight loss or any study endpoints – Systemic steroids for > 7 days – Insulin – Medications that affect metabolism of the study drug

– Strong inhibitors or inducers of CYP450 1A2 or 3A4 – Medications known to prolong the QTc interval

– Other investigational drugs or devices


What to Expect• Oral dose (tablet) once a day • 7 visits in 15 weeks

– Physical exam, vital signs, weight and waist circumference measurements and fasting blood collection / tests (Visits 1-7)

– Questionnaires for the caregiver to complete (Visits 1-7) – ECG (Visits 1, 6 and 7) – DXA Scan (Visits 2 and 7) – Height (Visits 2 and 7) – Diet, Physical Activity and Sleep Assessment (Visits 2-7)

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US Study Sites

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Stanford, Palo Alto CA

Seattle Children’s, Seattle WA

Rady Children’s Hospital / UCSD, San Diego CA

University of Florida, Gainesville FL

Children's Hospital Colorado, Aurora CO

Kansas University Medical Center, Kansas City KS

Children’s Minnesota, St. Paul MN

Vanderbilt University, Nashville TN

Winthrop University Hospital, Mineola NY

UH Medical Center, Cleveland OH

Boston Children’s Hospital, Boston MA

NICHD, Bethesda MD

Nationwide Children’s Hospital, Columbus OH

University of Utah, Salt Lake City UT

UCI, Irvine CA

Emory, Atlanta GA

Indiana University School of Medicine, Indianapolis IN

Sparrow Clinical Research Institute, Lansing MI

St. Joseph’s University Medical Center, Paterson NJ

| Confidential

UK Site Locationsmay be we should move this up to introductions.


Study Status

• 19 active sites in the US (7 in the UK) • Enrollment in progress

– Expect to complete around the end of the year • > 90% patients completing study enrolled in C602 • C602 duration increased from 9 to 12 months • Two reviews of data by independent DSMB

– No modifications to study, continue as planned

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Questions & AnswersClinicaltrials.gov NCT03440814

Soleno Therapeutics, Inc. C601 Project Manager 650-353-2051 [email protected]

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