Santhera - solutions for rare neuromuscular and pulmonary diseases - Fall 2019 Last update: 3 Nov 2019
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Santhera – solutions for rare
neuromuscular and pulmonary diseases
Fall 2019
Last update: 3 Nov 2019
Disclaimer
This presentation is not and under no circumstances to be construed as a solicitation, offer, or recommendation, to buy or sell
securities issued by Santhera Pharmaceuticals Holding AG. Santhera Pharmaceuticals Holding AG makes no representation (either
express or implied) that the information and opinions expressed in this presentation are accurate, complete or up to date. Santhera
Pharmaceuticals Holding AG disclaims, without limitation, all liability for any loss or damage of any kind, including any direct,
indirect or consequential damages, which might be incurred in connection with the information contained in this presentation.
This presentation expressly or implicitly contains certain forward-looking statements concerning Santhera Pharmaceuticals Holding
AG and its business. Certain of these forward-looking statements can be identified by the use of forward-looking terminology or by
discussions of strategy, plans or intentions. Such statements involve certain known and unknown risks, uncertainties and other
factors, which could cause the actual results, financial condition, performance or achievements of Santhera Pharmaceuticals
Holding AG to be materially different from any expected results, performance or achievements expressed or implied by such
forward-looking statements. There can be no guarantee that any of the research and/or development projects described will
succeed or that any new products or indications will be brought to market. Similarly, there can be no guarantee that Santhera
Pharmaceuticals Holding AG or any future product or indication will achieve any particular level of revenue. In particular,
management’s expectations could be affected by, among other things, uncertainties involved in the development of new
pharmaceutical products, including unexpected preclinical and clinical trial results; unexpected regulatory actions or delays or
government regulation generally; the Company’s ability to obtain or maintain patent or other proprietary intellectual property
protection; competition in general; government, industry, and general public pricing and other political pressures. Santhera
Pharmaceuticals Holding AG is providing the information in this new release as of the date of the publication, and does not
undertake any obligation to update any forward-looking statements contained herein as a result of new information, future events
or otherwise.
2 Company Presentation| November 2019
Vision and Strategic Focus
• Santhera aims to provide innovative medicines for treatment of rare
neuromuscular and pulmonary diseases
• Santhera has experience in European product launch for rare disease
(Raxone® for the treatment of rare ophthalmology disease LHON)
• Divestment of ophthalmology business Raxone® provided funding to
focus pipeline on near-term growth potential
Near-term strategic focus to advance two products (idebenone and vamorolone) towards approval as
treatments for patients with Duchenne Muscular Dystrophy: market entries in Europe and US 2020-2022
3 Company Presentation| November 2019
Capabilities from development to commercial sales
Clinical Bio. Medical Drug
Safety
Science Stats Affairs & PV
Non- Clinical Reg. Market Comm.
Clinical Operat. Affairs Access Operat.
Patient Technic. Supply Marke-
Advoc. Dev. Chain ting
Management
Human Resources, Communication
Administration, Finance
Legal Compliance, Quality Assurance
4 Company Presentation| November 2019
Santhera’s product pipeline
Santhera Pipeline Drug Preclin. Phase I PoC Pivotal Filing Market
Neuro-ophthalmological Diseases
Leber’s Hereditary Optic Neuropathy Idebenone Raxone®
Neuromuscular Diseases
Duchenne Muscular Dystrophy (GC non- users) Idebenone CMA/EU
Duchenne Muscular Dystrophy (GC users) Idebenone ongoing
Duchenne Muscular Dystrophy Vamorolone ongoing
Congenital Muscular Dystrophy Omigapil completed
Congenital Muscular Dystrophy, Type 1A Gene Therapy
Pulmonary Diseases
Cystic Fibrosis POL6014 ongoing
to be
AAT, NCFB, PCD, COPD POL6014
explored
GC: Glucocorticoid; CMA: conditional marketing authorization; AAT: Alpha-1 antitrypsin deficiency; NCFB: Non-cystic fibrosis bronchiectasis;
PCD: primary ciliary dyskinesia; COPD: Chronic Obstructive Pulmonary Disease
*Raxone® (150 mg idebenone) is approved in the Europe, Israel, Serbia for the treatment of visual impairment in adolescent and adult patients with LHON
5 Company Presentation| November 2019
License agreement with Chiesi Group for Raxone® in LHON 6 Company Presentation| November 2019
Strategic consideration of this license agreement
• Product pipeline in neuromuscular and
• Successful expansion of Santhera
pulmonary diseases provides key inflection
product pipeline in neuromuscular
points
and in 2020
pulmonary diseases
‒ EMA decision and product launch for
Puldysa® in DMD
• ‒ Upfront payment
Vamorolone ofstudy
pivotal CHF 50m andin DMD
readout
future milestone payments allows
‒ Start of Phase 2 with POL6014 in CF
focus and advancement of
neuromuscular and pulmonary
• Upfront andpipeline
product future milestone payments will
towards inflection
be points
invested in advancing neuromuscular and
pulmonary product pipeline towards key
inflection points
7 Company Presentation| November 2019
Product pipeline for neuromuscular diseases
Santhera Pipeline Drug Preclin. Phase I PoC Pivotal Filing Market
Neuro-ophthalmological Diseases
Leber’s Hereditary Optic Neuropathy Idebenone Raxone®
Neuromuscular Diseases
Duchenne Muscular Dystrophy (GC non- users) Idebenone CMA/EU
Duchenne Muscular Dystrophy (GC users) Idebenone ongoing
Duchenne Muscular Dystrophy Vamorolone ongoing
Congenital Muscular Dystrophy Omigapil completed
Congenital Muscular Dystrophy, Type 1A Gene Therapy
Pulmonary Diseases
Cystic Fibrosis POL6014 ongoing
to be
AAT, NCFB, PCD, COPD POL6014
explored
GC: Glucocorticoid; CMA: conditional marketing authorization; AAT: Alpha-1 antitrypsin deficiency; NCFB: Non-cystic fibrosis bronchiectasis;
PCD: primary ciliary dyskinesia; COPD: Chronic Obstructive Pulmonary Disease
*Raxone® (150 mg idebenone) is approved in the Europe, Israel, Serbia for the treatment of visual impairment in adolescent and adult patients with LHON
8 Company Presentation| November 2019
Pipeline synergies between idebenone and vamorolone for
the treatment of patients with Duchenne Muscular Dystrophy
• Combination of vamorolone and idebenone addresses medical need of DMD patients at all disease stages
• Vamorolone and idebenone could be used in all patients (not restricted to certain mutations)
• Combination therapy to be evaluated
vamorolone
Disease
ambulatory
progression in
function
patients with
DMD age [y] 0-5 5-10 10-15 15-20 20-25 > 25
respiratory
function
idebenone
9 Company Presentation| November 2019
Idebenone
in Duchenne Muscular Dystrophy (DMD)
Neuromuscular Diseases
Anthony, patient living with DMDMedical need for effective treatment of respiratory illness
in advanced patients with DMD
• Increasing respiratory muscle weakness
in DMD leads to:
Progressive respiratory function loss
‒ Decreased lung volumes and flow rates results in need for assisted ventilation
‒ Decreased ability to cough effectively and
clear airways from mucus
‒ Increased risk of airway infections
• There are no pharmacological therapies
approved specifically for treating
respiratory decline
• ~35,000 patients combined in US and Europe
11 Company Presentation| November 2019Puldysa®: Application for Conditional Marketing Authorization
in Europe
• Extensive pre-discussion of new data and overall regulatory path with national European regulatory
authorities and EMA
• New data from patients treated with idebenone and natural history studies close previous data gaps
• Puldysa® will be global tradename for DMD
12 Company Presentation| November 2019Placebo-controlled DELOS trial showed that idebenone
preserved respiratory function over 12 months
• Idebenone slowed loss of expiratory respiratory
function (peak expiratory flow, PEF%p) and met the
study primary endpoint 1,2
• Consistent treatment effects were seen for inspiratory
function (inspiratory flow reserve, IFR) and global
respiratory function (forced vital capacity, FVC%p) 1,3, 4
• Idebenone also reduced the risk of bronchopulmonary
adverse events (such as airway infections), the need of
systemic antibiotic treatment and risk of hospitalization
due to respiratory complications 5
1) Buyse et al. 2015; Lancet 385:1748-57;
2) Buyse et al. 2018; J Neuromuscular Diseases 5: 419–430.; PEF%p: peak expiratory flow percent predicted
3) Mayer et al. 2017; J Neuromuscular Diseases. 4:189-98.; FVC%p: forced vital capacity percent predicted
4) Buyse et al., 2017; Pediatric Pulmonology 52:508-515;
5) McDonald et al., 2016; Neuromuscular Disorders 26: 473–480
13 Company Presentation| November 2019SYROS real-world data: Idebenone treatment showed
persistent effect on respiratory function for up to 6 years
• Idebenone treatment showed a
persistent effect in slowing
decline in FVC%p for up to 6
years
• Annual decline in FVC%p in
patients on idebenone was
consistently smaller than in
untreated patients from a
matched external control group
(from CINRG Duchenne natural
Observed annual decline Expected annual decline for history study)
under idebenone treatment untreated patients
Mayer et al. 2019; Poster presented at MDA Clinical and Scientific Conference; April 2019
14 Company Presentation| November 2019Puldysa® - estimated time to market
2019 2020 2021 2022
Puldysa® (idebenone) Phase III SIDEROS trial in GC users
MA Application Q2 GC non-users Q4 GC users
Approval of MA Q2 Q3
Launch Q3 Q4
NDA Filing Q4 all patients
NDA Approval Q3
Launch Q4
Protection and regulatory status Competitive positioning and sales potential
• Orphan drug protection: USA (7y) and EU (10y) • Idebenone targets treatment of older patients
• Fast track designation in USA • Puldysa®: first treatment specifically for
respiratory complications
NDA: new drug application; MAA: marketing authorization application
15 Company Presentation| November 2019Vamorolone
in Duchenne Muscular Dystrophy (DMD)
Neuromuscular Diseases
Partnership withVamorolone: a transformational opportunity for Santhera
• Glucocorticoids (GCs) are recognized standard of care in children and adolescent patients with DMD
• High-dose GCs have severe systemic side-effects preventing lifelong treatment
• Regulators and patients/families seek better tolerable alternatives to the current GCs
• Vamorolone is a first-in-class therapy with a potential as new standard of care for DMD
• Basis for approval of vamorolone in DMD will be existing successful Phase IIa trial data and results
from ongoing Phase IIb trial
• Perfect strategic fit: vamorolone complements idebenone as treatment for DMD
17 Company Presentation| November 2019Vamorolone – revolutionizing mode of action
• Discovered and developed by
• First-in-class dissociative steroidal anti-inflammatory drug
• Different pharmacological properties distinguish vamorolone from standard glucocorticoids
MR: mineralocorticoid receptor GR: glucocorticoid receptor GC: glucocorticoid
Data from Heier et al. (2018); DOI 10.26508/lsa.201800186
18 Company Presentation| November 2019Vamorolone – current efficacy and safety data
Effects of vamorolone in animal model for DMD:
• Retains GC-type anti-inflammatory efficacy and reduces dystrophy, improves muscle strength and motor function
• Reduced stunting of growth, bone symptoms, cardiac side effects
Effects of vamorolone in Phase I trial 1 of healthy volunteers and Phase IIa trial 2,3 in patients with DMD:
• Vamorolone was well tolerated at all dose levels (up to 20mg/kg/d)
• Vamorolone shows efficacy in patients with DMD comparable to standard glucocorticoids (GCs)
• Reduced GC-class side effects (weight gain, bone fragility, metabolic disturbance, immune suppression)
• 6-months and 18-months open label extension data show that vamorolone is well tolerated leading to
improvement in gross motor function
GC: glucocorticoid steroid
1. Hoffman EP et al., Steroids (2018), 134: 43-52
2. Conklin LS, et al. Pharmacological Research(2018), 136: 140–150
3. Hoffman EP et al. Neurology (2019): doi:10.1212/WNL.0000000000008168
19 Company Presentation| November 2019Vamorolone – pivotal Phase IIb trial (VBP15-004), ongoing
The Vision-DMD trial by ReveraGen
Design Phase IIb randomized, double-blind, parallel group, placebo-
and active-controlled study with double-blind extension
Participants 120 ambulant boys ages 4 toEstimated time to market
2019 2020 2021 2022
Vamorolone Phase IIb VISION-DMD Trial
NDA Filing Q4
NDA Approval Exercise option to rights Q3
for vamorolone
Launch Q4
MA Application Q1
MA Approval Q1
Launch Q2
Protection and regulatory status Competitive positioning and sales potential
• Orphan drug protection: USA (7y) and EU (10y) • Vamorolone to become standard of care
• Method of use patent until 2029 (by country)
• Fast track designation in USA
NDA: New Drug Application; MAA: Marketing Authorization Application
21 Company Presentation| November 2019Product pipeline for neuromuscular diseases
Santhera Pipeline Drug Preclin. Phase I PoC Pivotal Filing Market
Neuro-ophthalmological Diseases
Leber’s Hereditary Optic Neuropathy Idebenone Raxone®
Neuromuscular Diseases
Duchenne Muscular Dystrophy (GC non- users) Idebenone CMA/EU
Duchenne Muscular Dystrophy (GC users) Idebenone ongoing
Duchenne Muscular Dystrophy Vamorolone ongoing
Congenital Muscular Dystrophy Omigapil completed
Congenital Muscular Dystrophy, Type 1A Gene Therapy
Pulmonary Diseases
Cystic Fibrosis POL6014 ongoing
to be
AAT, NCFB, PCD, COPD POL6014
explored
GC: Glucocorticoid; CMA: conditional marketing authorization; AAT: Alpha-1 antitrypsin deficiency; NCFB: Non-cystic fibrosis bronchiectasis;
PCD: primary ciliary dyskinesia; COPD: Chronic Obstructive Pulmonary Disease
*Raxone® (150 mg idebenone) is approved in the Europe, Israel, Serbia for the treatment of visual impairment in adolescent and adult patients with LHON
22 Company Presentation| November 2019Gene Therapy for LAMA2-deficient
Congenital Muscular Dystrophy (CMD)
(MDC1A)
Olivia, patient living with MDC1AMDC1A is a severe form of CMD with no approved treatment
• Rare genetic congenital muscular dystrophy (CMD)
• Progressive and life-threatening muscle weakness
• Mutations in LAMA2 gene
dysfunctional laminins
instability of muscle fibers
‒ Dysfunctional laminins MDC1A Muscle
‒ Dysfunctional dystroglycans Dystroglycanopathies
‒ Dysfunctional dystrophin Duchenne MD
Neuromuscul Disord. 2017, 27(9), p793 Gene reviews www.ncbi.nlm.nih.gov/books/NBK97333/
24 Company Presentation| November 2019Gene technology corrects muscular dystrophy in mouse model
Simultaneous Expression of Artificial Linkers (SEAL)
• Designed linker proteins act in conjunction to compensate gene defect
• Improvements in muscle force & survival with gene therapy
• Santhera and University of Basel collaborate to advance SEAL technology into the clinic
αLNNd Simultaneous
with SEAL Expression of
mag Artificial Linkers
Survival
Disease model
25 Company Presentation| November 2019Product pipeline for pulmonary diseases
Santhera Pipeline Drug Preclin. Phase I PoC Pivotal Filing Market
Neuro-ophthalmological Diseases
Leber’s Hereditary Optic Neuropathy Idebenone Raxone®
Neuromuscular Diseases
Duchenne Muscular Dystrophy (GC non- users) Idebenone CMA/EU
Duchenne Muscular Dystrophy (GC users) Idebenone ongoing
Duchenne Muscular Dystrophy Vamorolone ongoing
Congenital Muscular Dystrophy Omigapil completed
Congenital Muscular Dystrophy, Type 1A Gene Therapy
Pulmonary Diseases
Cystic Fibrosis POL6014 ongoing
to be
AAT, NCFB, PCD, COPD POL6014
explored
GC: Glucocorticoid; CMA: conditional marketing authorization; AAT: Alpha-1 antitrypsin deficiency; NCFB: Non-cystic fibrosis bronchiectasis;
PCD: primary ciliary dyskinesia; COPD: Chronic Obstructive Pulmonary Disease
*Raxone® (150 mg idebenone) is approved in the Europe, Israel, Serbia for the treatment of visual impairment in adolescent and adult patients with LHON
26 Company Presentation| November 2019POL6014 in Cystic Fibrosis (CF) Pulmonary Diseases
Cystic fibrosis, a rare inherited lung disease
• CF is a progressive, genetic disease leading to thick mucus in the lung (airway obstruction)
• This results in persistent lung infections, chronic inflammation and loss of respiratory function
Obstruction Infection
Genetic Defect Respiratory
RespiratoryFailure
Failure
Inflammation
• The disease is diagnosed in young children, about 70,000 patients worldwide
• Current treatments do not specifically address the chronic, underlying inflammation
28 Company Presentation| November 2019Targeting elastase to treat chronic lung inflammation
• Inflammation causes excessive production of neutrophil elastase (hNE)
POL6014
• POL6014 is a reversible and selective inhibitor of hNE
• POL6014 presents an opportunity for a pipeline in a product
• Phase Ib, multiple ascending dose (MAD) trial in CF patients is ongoing
• Preparation for a Phase II efficacy trial started
eFlow Nebulizer
29 Company Presentation| November 2019Summary
• Santhera established as specialty pharma company with focus on drugs
for rare diseases (neuromuscular and pulmonary)
• License agreement with Chiesi Group provided non-dilutive funding to
focus and advance late stage product pipeline
• Conditional Marketing Authorization Application for Puldysa® in
patients with DMD submitted to EMA, decision expected mid 2020
• Pipeline in DMD expanded with option to acquire license to vamorolone with the potential to become
standard of care
• Research collaboration to advance gene therapy for congenital muscular dystrophy (CMD)
• Innovative peptide product for the treatment of CF in early stage clinical development
30 Company Presentation| November 2019THEIR FUTURE OUR FOCUS
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