Saniona Pioneering Ion Channel Development For The Treatment of - - PowerPoint PPT Presentation

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Saniona

Pioneering Ion Channel Development For The Treatment of Rare Diseases

Corporate presentation, June 2020

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Saniona Executive Team

Jørgen Drejer, PhD

Chief Scientific Officer

Anita Milland

Interim Chief Financial Officer

Rami Levin, MBA

President & Chief Executive Officer

Rudolf Baumgartner, MD

Chief Medical Officer & Head

• f Clinical Development

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Saniona Investment Highlights

Clinical stage Biopharmaceutical company focused on rare diseases of the central nervous system with high unmet medical need Late stage treatment in development for two rare eating disorders: Prader Willi Syndrome (PWS) and Hypothalamic Obesity (HO)

• PWS: Pre IND meeting with FDA took place in May, Phase 2b study expected to begin in late Q4 2020
• HO: Positive Phase 2 top-line results released on April 22, 2020

Unique ion-channel drug discovery platform:

• SAN711 – For rare neuropathic itching disorders (e.g. brachioradial pruritus), entering phase 1
• SAN903 – For rare inflammatory and fibrotic disorders (e.g. idiopathic pulmonary fibrosis)

Delivering additional value through strategic partnerships

• Tesofensine for obesity
• CAD-1883 for essential tremor and Ataxia
• GABAa5 for schizophrenia

An experienced executive leadership team with a combined experience of over 80 years in the pharmaceutical

• industry. Experience in research, development and commercialization of rare disease drugs, both in the US and

EU

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Unique Ion-Channel Drug Discovery Platform

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Product Indication Preclinical Phase 1 Phase 2a Phase 2b Phase 3 Upcoming Milestones

Proprietary pipeline:

Tesomet

(tesofensine + metoprolol)

Prader-Willi syndrome

• Pre-IND meeting expected in Q2, 2020
• Ph2b expected to start by end of 2020

Hypothalamic obesity

• Pre-IND meeting expected in H2, 2020

SAN711

(GABA α3 PAM)

Rare neuropathic itching disorders

• Ready to enter phase 1

SAN903 (IK channel blocker) Rare inflammatory disorders

• IND Filling

Partnerships and out licensing

Tesofensine Obesity

• Out licensed to Medix (Mexico and

Argentina)

• Expected approval and Launch in H2,

2020

CAD-1883 (SK PAM) Essential tremor

• Out licensed to Cadent Therapeutics
• Minority stake & royalties

Ataxia BI-candidate (GABA α5 NAM) Schizophrenia

• Upfront: 5M €
• Milestones: 85M €
• Royalties

Proprietary Pipeline and Strategic Partnerships/Out Licensing

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Tesomet – a true Triple Monoamine re-uptake Inhibitor Controls Eating

Tesomet increases levels of monoamines by blocking re- uptake Reduces hyperphagia by controlling appetite and craving for food Increases metabolic rate Addresses significant unmet needs in Prader Willi Syndrome and Hypothalamic Obesity Tesomet

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Prader-Willi Syndrome (PWS)

“Therefore, patients are more available to other activities, and life as a whole becomes easier for the patients and their families.” Dóra Török Primary Investigator “Weight gain, hyperphagia and obsession with food are the greatest burden on both patients with Prader-Willi syndrome and their families. Tesomet helps to control weight and appetite and it decreases preoccupation with food.”

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Prader-Willi Syndrome, a Debilitating, Rare Genetic Disorder

Patient Population Birth incidence: 1 in 10,000 – 30,000 1 ~200,000 people worldwide are affected2 Cause Absence of paternally expressed genes at Chromosome 15 (q11-q13) Disease Characteristics Hyperphagia, insatiable hunger Short life expectancy, median 30-40 years3 Complications from hyperphagia Obesity related comorbidities Intellectual disabilities, physical deficiencies, behavioral problems Significant burden on caregivers and families

1National organization of Rare Diseases 2International Prader Willi Syndrome Organization 3Manzardo, A., Loker, J., Heinemann, J. et al. Survival trends from the Prader–Willi Syndrome Association

(USA) 40-year mortality survey. Genet Med 20, 24–30 (2018) doi:10.1038/gim.2017.92

USA 8,000-11,0001,2 Europe 13,000-18,0001,2

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Tesomet: Phase 2a Study Design in Prader-Willi Syndrome

Study Overview Two-center, randomized, double-blind, placebo controlled trial Upon completion of adult enrollment (n=9), adolescent patients enrolled (n=9)

Double-blind Open-Label Extension 1 (OLE 1) Open-Label Extension 2 (OLE 2)

Adults Adolescents

Tesomet (0.125 mg) Placebo Tesomet (0.125 mg) Tesomet (0.25 mg) Tesomet (0.5 mg) Placebo

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Significant reduction in hyperphagia scores in phase 2a PWS study

Adults: Tesomet 0.5 mg reduced the hyperphagia score to zero in a double-blind study Adolescents: Hyperphagia is down to low single digits at 0.25 mg per day during OLE 2

N=2 N=5 N=6 N=3 N=2 N=2 N=6 N=2 P<0.05

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Significant reduction in body weight and correlation to plasma levels, in phase 2a PWS study

• The 0.5 mg dose in adults showed promising efficacy
• The 0.125 mg dose in adolescents did not show

efficacy on primary endpoint - likely due to too low exposures of tesofensine

• A weight reduction was seen in OLE 2 where patients

were at the target plasma levels of tesofensine

adults adolescents

0.5 mg (n=9) 0.125 mg (n=9) 0.25 mg (n=3) 0.125 mg (n=1)

OLE-2

ANCOVA, Change from baseline to Day 91, LOCF

3 months 3 months 3 months

• 6
• 4
• 2

2 4 6

• 2.6

2.9 3.6 0.4

• 5.6

% change in body weight (adults & adolescents)

change in weight (%) Tesomet Placebo

• Highly statistically significant negative

correlation between weight loss and plasma concentration

% change in body weight (adults & adolescents)

P<0.05 0.125 mg 0.25 mg

p=0.003 (intercept) p=0.005 (slope)

Random Co-Efficient Analysis PK versus % Monthly Weight Change

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Conclusions of phase 2a results of Tesomet in Prader Willi Syndrome

Study Design

• 18 patients dosed and followed

up to 9 months

• Three doses investigated:

0.125mg, 0.25mg and 0.5mg

Main Efficacy Findings

• Significant reduction in

hyperphagia score

• 2.6% reduction in body weight
• n the 0.25mg dose by the end of

the study

• Good correlation between

efficacy, dose and plasma level

Main Safety Findings

• 0.125mg and 0.25mg doses

were safe and well tolerated

• Higher than expected drop-out

rates were observed at a dose of 0.5mg

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Planned Study Overview 16-week blinded placebo-controlled study; 36-week open label extension with dose adjustment 144 patients Phase 2b top-line data readout expected in Q2 2022

Pivotal PWS Clinical Program with Overlapping Program Design

2020 2021 2022

NDA Submission & FDA review

Phase 2b Pivotal Trial

2023

Placebo 0.125mg 0.25mg 0.375mg Switch to 0.25mg Continue/Increase dose to 0.25mg Continue/Change to 0.125mg or 0.375mg Continue/Decrease to

• 0. 25mg or 0.125mg

36-week open label 16-week double blind (including recruitment)

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Competitive Landscape: PWS Clinical Trials Targeting Hyperphagia

Program Development Stage Administration Clinical Results in PWS Primary Efficacy Endpoints

Saniona (Tesomet) Monoamine reuptake Inhibitor Phase 2b/3 to start by end of 2020 Once daily tablet Ph2 (up to 9 months): Positive efficacy results, impact on hyperphagia and weight loss Soleno Therapeutics (CR Diazoxide) KATP opener Phase 3 Once daily tablet Ph2 (10 weeks): Effect on hyperphagia in open label study, but no difference in placebo-controlled part Levo Therapeutics (Carbetocin) Oxytocin analogue Phase 3 3 times daily intranasal (cooled container) Ph2 (2 weeks): reduction in hyperphagia only Millendo Therapeutics (Livoletide) Ghrelin analogue Phase 2b/3 As per press release issued on April 6:

• The study failed for

lack of efficacy on primary endpoint

• Clinical program in

PWS discontinued Daily injection Ph2 (2 weeks). Small reduction in hyperphagia

• nly

No drug currently approved to treat hyperphagia in PWS

Hyperphagia Weight Loss Obsessive Behavior

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Hypothalamic Obesity (HO)

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Hypothalamic Obesity, an Acquired Eating Disorder

Patient Population Prevalence ~1 in 50,000-100,0001 Cause 50% of patients acquire HO post craniopharyngioma2 Disease characteristics Post surgical obesity and hyperphagia, insatiable hunger Memory impairment, attention, impulse control Depression and suicide

1Garnett, M.R., Puget, S., Grill, J. et al. Craniopharyngioma. Orphanet J Rare Dis 2, 18 (2007) doi:10.1186/1750-1172-2-18 2Roth, C., Hypothalamic Obesity in Craniopharyngioma Patients, J. Clin. Med. 2015, 4(9), 1774-1797; https://doi.org/10.3390/jcm4091774

USA 3,400 – 6,8001 Europe 5,500 – 11,0001

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Tesomet: Phase 2 Study in Hypothalamic Obesity

Study Overview

A 24-week phase 2, double-blind, randomized, placebo-controlled, single-center safety and efficacy study to evaluate overall safety and tolerability of Tesomet in patients with hypothalamic obesity (HO), followed by a 24-week open-label extension 21 patients randomized into the trial. 2:1 randomization (Active:Placebo)

Placebo Placebo crossover Tesomet* 0.5mg 24-weeks double blind 24-weeks open label

2020 2021

Phase 3

FDA FDA filing

2022

Phase 2 Phase 3

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Primary and Secondary Endpoints

Primary endpoint:

Safety and tolerability will be judged from all safety data collected in the period, including number and type of treatment emergent adverse events, laboratory data, BP and HR.

Secondary endpoints:

Change in body weight from baseline to week 24 Change in waist circumference from baseline to week 24 Change in body composition body fat mass and lean body mass by DEXA-scan from baseline to week 24 Change in glycemic control and lipid profile from baseline to week 24 Change in satiety and appetite using the composite satiety score (CSS) from baseline to week 24 Change in HR and BP from baseline to week 24 Change of 24h BP from baseline to week 24 and by home monitoring

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Subject disposition

Disposition Tesomet Placebo Total Screened 35 Randomized 13 8 21 Completed DB part 12 6 18 Discontinued 1 2 3 Reasons for discontinuation: SAE 1 1 AE 1 1 Withdrew consent 1 1

SAE- Hyponatremia; AE-Dry Mouth

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Safety and Tolerability

Tesomet was found to be safe and well tolerated. Sleep problems, dry mouth, and headache were seen more frequently in patients treated with Tesomet. These are all well-known effects associated with tesofensine and/or metoprolol. There was a single case of Tesomet related anxiety reported as a severe adverse event and associated with an AE of paranoia in a patient with a 5-year history of anxiety which resolved after discontinuation of treatment. There were no significant or clinically meaningful differences in heart rate or blood pressure between treatment groups. 18 of the 21 patients enrolled completed the placebo-controlled part of the study (2 drop-outs in placebo; 1 drop-out in treatment group). All 18 continued into open label extension.

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Change in Weight From Baseline to Week 24

Baseline values (kg) and mean (range): Tesomet: 114.12 (86.1 – 144.4) Placebo: 112.16 (80.4 – 163.1)

Treatment with Tesomet led to a statistically significant and clinically meaningful reduction in bodyweight compared to placebo at week 12 (p=0.0158), week 16 (p=0.0195), week 20 (p=0.0242), and at week 24 (p=0.0169) with a 6.28% average reduction.

6.28% p=0.0169 p=0.0158 p=0.0195 p=0.0242

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The analyses focused on endpoints specified in the FDA’s Guidance for Industry Developing Products for Weight Management were also positive. The guidance requires: A statistically significant difference in >5% in body weight loss from baseline between active- and placebo-treated patients. The proportion of Tesomet-treated patients with >5% change in body weight (n=8; 61.5%) compared to placebo (n=1; 12.5%) was statistically significant (p=0.046).-ACHIEVED At least 35% of patients in the active treatment group to achieve > 5% in body weight loss from baseline. Per above, this was achieved in 61.5% of Tesomet-treated patients.-ACHIEVED The proportion of patients with >5% in body weight loss in the active group to be at least twice that of the placebo group. Per above, the 61.5% of Tesomet-treated patients to achieve this goal is more than twice the 12.5% in the placebo group.-ACHIEVED

% of Patients with > 5% and >10% Decrease in Bodyweight at Week 24

Proportion of Patients with > 5% and >10 weight loss at week 24

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Change in Waist Circumference from Baseline to Week 24

Baseline values (cm) and mean (range):

Tesomet: 117.5 (99 – 142) Placebo: 116.1 (89 – 142)

Treatment with Tesomet led to statistically significant and clinically meaningful reductions in waist circumference compared to placebo at week 16: 3.45% (p=0.0348), week 20: 4.442% (p=0.0221), and approached statistical significance at week 24: 5.04% (p=0.0519).

• 4.442%

P=0.0221

• 3.45%

P=0.0348

• 5.04%

p=0.0519

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Change in HbA1c from Baseline to Week 24

Baseline values (mmol/mol) and mean (range)

Tesomet: 41.385 (29.00 – 85.00) Placebo: 39.000 (33.00 – 43.00)

Tesomet treatment was associated with an estimated 12.2% reduction in hemoglobin A1c (HbA1c) compared to placebo (p=0.0713); this result was not statistically significant. However, it should be noted that the two diabetic patients in the treatment group showed marked lowering of HbA1c on treatment (mean 49%), whereas no change in HbA1c was seen in normoglycemic patients.

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Saniona Investment Highlights

Clinical stage Biopharmaceutical company focused on rare diseases of the central nervous system with high unmet medical need Late stage treatment in development for two rare eating disorders: Prader Willi Syndrome (PWS) and Hypothalamic Obesity (HO)

• PWS: Pre IND meeting with FDA took place in May, Phase 2b study expected to begin in late Q4 2020
• HO: Positive Phase 2 top-line results released on April 22, 2020

Unique ion-channel drug discovery platform:

• SAN711 – For rare neuropathic itching disorders (e.g. brachioradial pruritus), entering phase 1
• SAN903 – For rare inflammatory and fibrotic disorders (e.g. idiopathic pulmonary fibrosis)

Delivering additional value through strategic partnerships

• Tesofensine for obesity
• CAD-1883 for essential tremor and Ataxia
• GABAa5 for schizophrenia

An experienced executive leadership team with a combined experience of over 80 years in the pharmaceutical

• industry. Experience in research, development and commercialization of rare disease drugs, both in the US and

EU

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