Saniona Pioneering Ion Channel Development For The Treatment of Rare Diseases Corporate presentation, June 2020 1 |
Saniona Executive Team Rami Levin, MBA Anita Milland Jørgen Drejer, PhD Rudolf Baumgartner, MD President & Chief Executive Interim Chief Financial Officer Chief Scientific Officer Chief Medical Officer & Head Officer of Clinical Development 2 |
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 3 |
Unique Ion-Channel Drug Discovery Platform 4 |
Proprietary Pipeline and Strategic Partnerships/Out Licensing Product Indication Preclinical Phase 1 Phase 2a Phase 2b Phase 3 Upcoming Milestones Proprietary pipeline: • Pre-IND meeting expected in Q2, 2020 Prader-Willi syndrome Tesomet • Ph2b expected to start by end of 2020 (tesofensine + metoprolol) Hypothalamic obesity • Pre-IND meeting expected in H2, 2020 Rare neuropathic SAN711 • Ready to enter phase 1 itching disorders (GABA α3 PAM) SAN903 Rare inflammatory (IK channel • IND Filling disorders blocker) Partnerships and out licensing Out licensed to Medix (Mexico and • Argentina) Tesofensine Obesity Expected approval and Launch in H2, • 2020 Essential tremor • Out licensed to Cadent Therapeutics CAD-1883 • Minority stake & royalties (SK PAM) Ataxia • Upfront: 5M € BI-candidate Schizophrenia • Milestones: 85M € (GABA α5 NAM) • Royalties 5 |
Tesomet – a true Triple Monoamine re-uptake Inhibitor Controls Eating Tesomet 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 6 |
“Weight gain, hyperphagia “Therefore, patients are and obsession with food are more available to other the greatest burden on both activities, and life as a whole patients with Prader-Willi becomes easier for the syndrome and their families. patients and their families. ” Tesomet helps to control Dóra Török weight and appetite and it Primary Investigator decreases preoccupation with food.” Prader-Willi Syndrome (PWS) 7 |
Prader-Willi Syndrome, a Debilitating, Rare Genetic Disorder Patient Population Birth incidence: 1 in 10,000 – 30,000 1 ~200,000 people worldwide are affected 2 USA Europe 8,000-11,000 1,2 13,000-18,000 1,2 Cause Absence of paternally expressed genes at Chromosome 15 (q11-q13) Disease Characteristics Hyperphagia, insatiable hunger Short life expectancy, median 30-40 years 3 Complications from hyperphagia Obesity related comorbidities Intellectual disabilities, physical deficiencies, behavioral problems Significant burden on caregivers and families 1 National organization of Rare Diseases 2 International Prader Willi Syndrome Organization 8 | 3 Manzardo, 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
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) Open-Label Extension 1 Open-Label Extension 2 Double-blind (OLE 1) (OLE 2) Tesomet (0.5 mg) Adults Placebo Adolescents Tesomet (0.125 mg) Tesomet (0.125 mg) Tesomet (0.25 mg) Placebo 9 |
Significant reduction in hyperphagia scores in phase 2a PWS study Adults: Tesomet 0.5 mg reduced the hyperphagia Adolescents: Hyperphagia is down to low score to zero in a double-blind study single digits at 0.25 mg per day during OLE 2 N=2 N=2 N=3 N=2 P<0.05 N=6 N=6 N=5 N=2 10 |
Significant reduction in body weight and correlation to plasma levels, in phase 2a PWS study Random Co-Efficient Analysis % change in body weight (adults & adolescents) % change in body weight (adults & adolescents) PK versus % Monthly Weight Change 3 months 3 months 3 months 6 Tesomet change in weight (%) 3.6 0.5 mg 4 2.9 Placebo (n=9) 2 OLE-2 0.4 p=0.003 (intercept) 0 p=0.005 (slope) P<0.05 -2 0.125 mg (n=9) -2.6 -4 0.25 mg (n=3) -6 0.125 mg (n=1) -5.6 0.125 mg 0.25 mg adults adolescents ANCOVA, Change from baseline to Day 91, LOCF • 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 Highly statistically significant negative • exposures of tesofensine correlation between weight loss and plasma • A weight reduction was seen in OLE 2 where patients concentration were at the target plasma levels of tesofensine 11 |
Conclusions of phase 2a results of Tesomet in Prader Willi Syndrome Study Design Main Efficacy Findings Main Safety Findings - 18 patients dosed and followed - Significant reduction in - 0.125mg and 0.25mg doses up to 9 months hyperphagia score were safe and well tolerated - Three doses investigated: - 2.6% reduction in body weight - Higher than expected drop-out 0.125mg, 0.25mg and 0.5mg on the 0.25mg dose by the end of rates were observed at a dose of the study 0.5mg - Good correlation between efficacy, dose and plasma level 12 |
Pivotal PWS Clinical Program with Overlapping Program Design 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 2020 2021 2022 2023 16-week double blind (including recruitment) 36-week open label Switch to 0.25mg Placebo Phase 2b Pivotal Trial Continue/Increase dose 0.125mg to 0.25mg NDA Submission & FDA review Continue/Change to 0.25mg 0.125mg or 0.375mg Continue/Decrease to 0.375mg 0. 25mg or 0.125mg 13 | 13 |
Competitive Landscape: PWS Clinical Trials Targeting Hyperphagia No drug currently approved to treat hyperphagia in PWS Program Development Administration Clinical Results in PWS Primary Efficacy Endpoints Stage Obsessive Weight Hyperphagia Behavior Loss Saniona Phase 2b/3 to start by Once daily tablet Ph2 (up to 9 months): (Tesomet) end of 2020 Positive efficacy results, Monoamine impact on hyperphagia and reuptake Inhibitor weight loss Soleno Phase 3 Once daily tablet Ph2 (10 weeks): Effect on Therapeutics hyperphagia in open label (CR Diazoxide) study, but no difference in K ATP opener placebo-controlled part Levo Therapeutics Phase 3 3 times daily Ph2 (2 weeks): reduction in (Carbetocin) intranasal hyperphagia only Oxytocin analogue (cooled container) Millendo Phase 2b/3 Daily injection Ph2 (2 weeks). Small Therapeutics reduction in hyperphagia (Livoletide) only As per press release Ghrelin analogue issued on April 6: • The study failed for lack of efficacy on primary endpoint • Clinical program in PWS discontinued 14 |
Hypothalamic Obesity (HO) 15 |
Hypothalamic Obesity, an Acquired Eating Disorder Patient Population Prevalence ~1 in 50,000-100,000 1 USA Europe 3,400 – 6,800 1 5,500 – 11,000 1 Cause 50% of patients acquire HO post craniopharyngioma 2 Disease characteristics Post surgical obesity and hyperphagia, insatiable hunger Memory impairment, attention, impulse control Depression and suicide 1 Garnett, M.R., Puget, S., Grill, J. et al. Craniopharyngioma. Orphanet J Rare Dis 2, 18 (2007) doi:10.1186/1750-1172-2-18 2 Roth, C., Hypothalamic Obesity in Craniopharyngioma Patients, J. Clin. Med. 2015 , 4 (9), 1774-1797; https://doi.org/10.3390/jcm4091774 16 |
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) 2020 2021 2022 24-weeks double blind 24-weeks open label Placebo Placebo crossover Phase 2 Tesomet * 0.5mg FDA Phase 3 Phase 3 FDA filing 17 | 17 |
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