Santhera Pharmaceuticals - An emerging leader in neuromuscular diseases - January 2021
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Santhera Pharmaceuticals
An emerging leader in neuromuscular diseases
January 2021
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 Santhera Pharmaceuticals Holding AG'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 presentation 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 Santhera Jan 1, 2021
SIX Swiss Exchange listing since 2006 (SANN)
01
Global headquarters near Basel (Switzerland)
North American headquarters in Boston (USA)
Lead program vamorolone in Duchenne muscular dystrophy (DMD)
02
Potential foundational therapy for broad segment of DMD patients
Asset secured through option exercise (Sep 2020)
Santhera Lead asset after discontinuation of Puldysa in DMD (Oct 2020)
Pharmaceuticals New leadership team
03
Corporate Strong commercial emphasis
Snapshot US-listed biotech company experience
Recent financing activities
04
Cash and cash equivalents of CHF 10.2 million (October 31, 2020)
Highbridge Capital amended facility to provide up to an additional CHF 15 million
Current cash & financing facility provide runway to Q2-21
Finance raised earlier in 2020: IRIS equity linked CHF 12.0 million, Highbridge Capital CHF 7.5 m
Main shareholders: Idorsia, WDI Invest (Bertarelli family)
3 Santhera Jan 1, 2021
Vamorolone global rights offer an attractive investment opportunity
Vamorolone global rights secured in all Near term • Pivotal study fully enrolled and
indications via direct license from inflection point for 6-month data readout in Q2-2021
ReveraGen (Sep, 2020) attractive disease
• Substantial clinical package
area (DMD) with
supported by long term data
• New class of molecule with promise to provide high unmet need
alternative to standard steroidal treatments
• Peak sales potential > USD 500 million in DMD
alone, for combined US and EU markets
• Vamorolone in other high medical
• Geographical expansion through partnering for
need indications beyond
DMD indication
neuromuscular disorders
• Additional formulations planned to allow for Additional pipeline
value drivers • Lonodelestat (cystic fibrosis & other
differential dosing/pricing in non-DMD indications
pulmonary indications) and gene
• Orphan drug exclusivity and intellectual property therapy (congenital muscular
coverage with potential extension through 2033 dystrophy)
4 Santhera Jan 1, 2021Experienced executive management team with biotech
and big pharma background
Dario Eklund Andrew Smith Günther Metz Oliver Strub
CEO CFO Business Development Group General Counsel
P&L responsibility for global Corporate/operational finance Biotech/Pharma R&D Vast experience in all legal/
business >CHF 1 billion expert, broad experience in background G&A areas and complex
and >1’000 employees pharma/biotech cross-border transactions
Business dev. since 2008
CCO, Vifor Pharma, prev. CFO/COO at Allecra Head Corporate Law &
Preparation & execution of
Organogenesis, Sanofi, Therapeutics, CFO Sucampo Chief Compliance Officer,
all major Santhera
Novartis Pharma (US listed) Ciba Specialty Chem.
transactions
MSc FCMA MLaw
PhD
5 Santhera Jan 1, 2021Financial overview
• Cash available up to CHF 25 million for runway to Q2-21
• Cash and cash equivalents: CHF 10.2 million (October 31, 2020)
• Highbridge Capital Facility: CHF 15.0 million
• Operating cost reductions
• Restructuring Q4-20 resulting in 50% headcount annualised cost reductions: CHF 10 million
• Termination of Puldysa related activities with reduction in development and commercialization costs
• Share capital and market capitalization
• Issued share capital 19.3 million at CHF 2.84 (Jan 4, 2021) per share = market capitalization CHF 54.8 million
• Convertible bond
• CHF 60 million maturing February 2022 with 5% interest and conversion price of CHF 64.80
• Current market value CHF 18.0 million (30% of par value Jan 4, 2021)
6 Santhera Jan 1, 2021 All amounts Consolidated IFRSSanthera’s pipeline offers promising therapeutic options in
several rare disease areas
Development Stage
Indication Molecule Preclinical Ph 1 Ph 2 Pivotal Filing Market Milestones Remarks
Duchenne vamorolone Q2-2021 Licensed from
VISION - DMD
muscular dystrophy (oral suspension) Top line data expected ReveraGen
lonodelestat Q4-2020: Completion Licensed from
Cystic fibrosis
(inhaled) Ph1b expected Polyphor
Congenital Collab. Univ. Basel
Gene therapy Animal PoC ongoing
muscular dystrophy & Rutgers
Inflammatory diseases E.G. Preclinical biomarker Rationale for multiple
vamorolone
IBD, COPD, Asthma studies published diseases
Diseases associated with Rationale for multiple
lonodelestat Under evaluation
high hNE activity diseases
Vamorolone option rights assigned from Idorsia and license taken from ReveraGen in Sep 2020
IBD: Inflammatory Bowel Disease; COPD: Chronic Obstructive Pulmonary Disease
hNE: Human Neutrophil Elastase; Lonodelestat was formerly known as POL6014
PoC: Proof of Concept
7 Santhera Jan 1, 2021DMD is a rare genetic disorder with very limited treatment options
Genetics Patients Cause Symptoms Late stage
X-linked recessive, Affecting primarily Caused by loss of Associated with Early death due to
rare genetic boys at early age the protein chronic muscle cardio-respiratory
disorder and most with incidence of 1 dystrophin in damage, failure
common type of in 3,500 – 5,000 muscle cells as a inflammation and
muscular dystrophy male births result of genetic eventual loss of
mutations function
Diagnosis Loss of ambulation Death
Loss of respiratory function
Glucocorticoids Need for assisted ventilation
Age [years] 5 10 15 20 25
8 Santhera Jan 1, 2021 Birnkrant et al. (2018) Lancet Neurology, 1474-4422(18)30024-3 ; Cowen et al. BMC Neurology (2019) 19:84DMD offers attractive opportunity in well-defined orphan disease market
DMD market with few current treatment
options, projected to be worth Small teams
needed to cover DMD Centers HCPs
> USD 4 billion by 2023*
entire market in
US ~160 ~450
EU and US
• Approx. 30,000 – 35,000 patients in US and EU EU-5 ~180 ~750
combined
• Well defined standard of care with steroids as lead
chronic treatment • Exon skippers and read through
Current approved therapies serve niche segments based
• Patients diagnosed at early age and accessible
therapies on genetic mutation
• Limited number of specialized centers command high • Approved standard steroidal drug,
• Well organized and influential patient advocacy price, but will have deflazacort in US, achieves attractive
groups intrinsic barriers margins
9 Santhera Jan 1, 2021 * Grand View Research Inc., Research & Markets, Decision ResourcesSteroids are standard of care but face limitations due to side effects
Janet Woodcock (FDA) at PPMD conference March 2019*:
“Corticosteroids are just the most toxic anti-inflammatory (drug) we could possibly think about…”
Glucocorticoids (GC) are considered standard of care in DMD
but adverse events lead to high levels of discontinuations
GC non-user
• Used as chronic foundational treatment across all disease stages
GC user
• Time on drug severely limited by adverse events and patient choice
• Adverse effects include stunted growth, metabolic disorders, fractures
Vamorolone has been designed to offer the benefits of steroids for longer
• New class of molecule to retain benefit of glucocorticoids but uncouple efficacy from side effects
• Strategy aims to capture wide range of patients independent of mutation, alone or in combination with other therapies
• Pivotal Phase 2b trial (VISION-DMD, 121 patients, aged 4 - 7) completed enrollment with readout in Q2-2021
*https://www.parentprojectmd.org/ppmds-historic-compass-meeting/
10 Santhera Jan 1, 2021 PPMD: Parent Project Muscular Dystrophy ; Cowen et al. BMC Neurology 2019
Company illustration based on survival estimates and steroid use illustration McDonald CM, et al., Neuromuscular Disorders 2018Novel pharmacology of vamorolone drives differentiated clinical
benefit with improved safety profile
Vamorolone pharmacology
• Dissociative steroid designed to have retained anti-inflammatory efficacy and reduced steroid-associated side effects
• Unlike steroids, has antagonist properties on mineralocorticoid receptor pathways with potential for cardiac benefit in DMD
• Inherent membrane stabilizing properties supporting fragile muscle cell integrity
• Tolerability profile suitable for longer use as chronic therapy
Properties
Dissociative steroid
Mineralocorticoid receptor
antagonist
Corticosteroids Vamorolone
9,11-carbon-carbon single bond, 9,11-carbon-carbon double bond Membrane stabilizer
additional OH group
e.g. prednisone and deflazacort
Based on Mode of Action, preclinical and clinical research e.g. Heier 2013, Reeves 2013,
11 Santhera Jan 1, 2021
Damsker 2016, Garvin 2016, Hoffman 2018, Conklin 2018, Hoffman 2019, Heier 2019, Ortlund 2020, Smith 2020, Liu 2020Vamorolone is characterized by a well-defined and differentiated MoA
Vamorolone binds to the glucocorticoid receptor (GR) like standard steroids but in a different binding conformation
This subtle difference alters receptor properties and influences receptor mediated downstream gene expressions
It results in desired transrepression to reduce inflammation but weakens transactivation responsible for side effects
Transactivation 3
Glucocorticoids Bone fragility & fractures
NF-KB Reduced / delayed growth
Hypogonadism
Vamorolone
GRE Weight gain
Behavioral effects
Diabetes
Transrepression1,2 Cushingoid features
Hypertension
Reduced Muscle Inflammation Adrenal suppression
GRE=glucocorticoid response elements; NF-кB=nuclear factor kappa B;MoA: Mode of action
12 Santhera Jan 1, 2021 1. Barnes P. Pharmaceuticals. 2010;3:514-540. 2. Heier CR, et al. EMBO Mol Med. 2013;5:1569-1585.
3. Saag K, Furst DE. https://www.uptodate.com/contents/major-side-effects-of-systemic-glucocorticoidsVamorolone as an alternative to GCs offers a unique business
opportunity in DMD
• Glucocorticoids (GC) are standard of care in DMD, an attractive market with 30,000 - 35,000 patients in US and EU combined
• Based on the promising profile of vamorolone, both current GC users and current GC non-users are candidates for treatment
• We estimate peak sales potential > USD 500 million in US and major 5 EU markets combined
Illustration of glucocorticoid (GC) use as function of age and potential penetration for
vamorolone reaching approximately 1/3 of the prevalent population at peak
Prevalence of diagnosed
patients per given age
not on any glucocorticoid treatment
GC non-users treated with vamorolone
GC users switching to vamorolone
remaining on glucocorticoid treatment
13 Santhera Jan 1, 2021Vamorolone clinical development timeline and associated publications
Vamorolone pharmacology and clinical evidence has been published in > 20 peer reviewed articles
2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
Ph 1 (n=86) Ph 2a (n=48) Ph 2b (n=121) age 4 - 7 years 6m 12m
For For
Ph 2a Extension FDA EMA
filing filing
Ph 2a Long term extension
Hoffman et al
Ph 1 Biomarker
Conklin et al
Extensive published, preclinical Ph2a study Hoffman et al
Ph2a EXT 6m Smith et al
research package in DMD
Ph2a LTE 18m In prep.
and in additional indications
Ph2a LTE 30m
profiling vamorolone
Mavroudis et al
Li et al
Population PK Liu et al
PK-PD study
Mode of Action
14 Santhera Jan 1, 2021Phase 2a study and extensions indicate long-term efficacy and safety
Study in 48 steroid naive patients aged 4 - 7 years with 30 months open label extension
2 Weeks treatment (Conklin et al. 2018)
First dissociative steroid demonstrating anti-inflammatory efficacy
with steroid-associated safety concerns decreased
2 mg/kg/d
6 Months treatment (Hoffman et al. 2019) 6 mg/kg/d
Control
Dose related improvements in muscle function where 2.0 mg/kg/d 0.75 mg/kg/d
dose group meeting the primary outcome of (Time to Stand Test) 0.25 mg/kg/d
18 Months treatment (Smith et al. 2020)
Brackets indicate mixed-model repeated- measures p values (black for comparisons to Cooperative International Neuromuscular Research Group Duchenne Natural History
Brackets indicate mixed-model repeated-measures p values
Similar efficacy as corticosteroids as assessed by motor function Study [DNHS] external comparator; blue for within-trial dose group comparisons).
- black for comparisons to CINRG Duchenne Natural History Study [DNHS]
outcomes but with fewer reported AEs and no growth stunting - blue for within-trial dose group comparisons
30 Months treatment (data collection completed)
15 Santhera Jan 1, 2021 Conklin et al. Ph. Res. (2018); Hoffman et al. Neurology. (2019) ; Smith et al. PLOS Medicine. (2020)Ongoing pivotal Ph 2b study in patients with DMD is fully enrolled
Pivotal, randomized, double-blind, placebo controlled trial in 121 steroid-naive patients
• Developed under FDA and EMA scientific advice
• Boys aged 4 - 7 years in 4 groups
• 30 sites in US, EU, Canada, Australia, Israel
• Readout after 24 and 48 weeks
• 24 week readout Q2-2021
Outcome Primary outcome measure is timed function test: Time to Stand Test (Velocity)
measures
Plus secondary safety and efficacy parameters: Body Mass Index, cardiac function, 6MWT, NSAA, run/walk test
16 Santhera Jan 1, 2021 6MWT: six minute walk test; NSAA: North Star Ambulatory AssessmentNDA filing for vamorolone in DMD is expected in Q4-2021
VISION-DMD pivotal trial on track for 6-month data readout in Q2-2021
Regulatory incentives
Orphan Drug Designation (EU, US) & FDA Fast Track Designation
Rare Pediatric Disease Designation, eligibility for US Priority Review Voucher
2020 2021 2022 2023
TIMELINES
DMD
Q3 Q4 Q1 Q2 Q3 Q4 H1 H2 H1
VISION-DMD NDA Approval
Full enrollment Filing Launch
VISION DMD VISION DMD
Vamorolone Last patient 6-month
Long term last visit Top line data
VISION DMD
extension MA Approval
12-month
publication Application Launch
data
17 Santhera Jan 1, 2021 MoA: Mode of action; LTE: Long term extension; Smith 2020, Liu 2020Vamorolone is a platform product with wider potential
Current
Santhera
Focus
18 Santhera Jan 1, 2021 Company Assessment; Numbers reflect estimated number of US patients; Size of bubbles not scaled linearly with NInternational patents granted for DMD and other inflammatory diseases
ReveraGen has built a patent portfolio with applications covering potential claims in wide range of indications
• Granted use patents in key indications valid at least until 2029
• Eligibility for patent term extensions until 2033*
• Additional IP on technical development in planning
200+ indications mentioned
in patent applications
Inflammatory disease
Use of steroids
Indications Compounds
Status Expiry
claimed claimed 50+ indications with potential
Approx. 80 incl. granted in US, EU, CN, claims
vamorolone 05-2029
muscular dystrophy JP & more. Good rationale
Currently limited data
Approx. 80 incl. Analogs of granted in US, some
04-2031 Claims not granted yet
muscular dystrophy vamorolone indications
Approx. 150 incl. granted in US for approx. 20 indications with
vamorolone 11-2032
muscular dystrophy glioblastoma granted claims
Approx. 60 excl. Muscular dystrophies incl. DMD,
vamorolone all pending 06-2036
muscular dystrophy arthritis, inflammatory bowel
Muscular dystrophy vamorolone disease, chronic inflammatory lung
all pending 07-2039 disease, cardiovascular diseases
incl. DMD crystalline forms
multiple sclerosis, brain tumors
19 Santhera Jan 1, 2021 *https://www.uspto.gov/web/offices/pac/mpep/s2750.html;Lonodelestat in Phase 1b – a promising treatment option for cystic
fibrosis (CF) by directly targeting chronic inflammation
Lonodelestat
bound to
Current treatments in CF do not specifically address the
elastase chronic, underlying inflammation
Lonodelestat is a very potent and highly selective inhibitor of
human neutrophil elastase, a key enzyme in inflammation
Development in CF Opportunities beyond CF
Asset was licensed from Polyphor for global rights Applicable to diseases associated with high levels of elastase
in all indications e.g. Non-CF bronchiectasis, Alpha-1-Antitrypsin Deficiency, Lung
cancer, Chronic Obstructive Pulmonary Disease, Acute
Program supported by funding from the CF Foundation
Respiratory Distress Syndrome
Two Phase 1 single ascending dose (SAD) trials
Broad patent portfolio and exclusive collaboration with PARI for
successfully performed
inhaled formulation and nebulizer device
Phase 1b, multiple ascending dose (MAD) trial in CF patients
expecting completion in Q4-2020 and data available early 2021
20 Santhera Jan 1, 2021 Polverino, Chest 2017; Crocetti, Exp Opin Th Patents 2019; Barth, J. Cys. Fibr. 2019; Lerman, Steroids 2018Santhera pipeline offers an attractive investment opportunity
• Current valuation doesn’t reflect
Vamorolone with near term inflection Finance pipeline potential
point for attractive disease area (DMD)
• Overhang from convertible bond to
with high unmet need
be addressed
• Current cash & financing facility
• New class of molecule with promise to provide
provide runway to next inflection
alternative to standard steroidal treatments
point of pivotal readout in Q2-2021
• Pivotal study fully enrolled and 6-month data
readout in Q2-2021
• US NDA filing planned for Q4-2021 • Vamorolone and lonodelestat – two
Additional value
• EU MAA filing planned for H1-2022 products with broad range of further
drivers
partnering & pipeline opportunities
• Peak sales potential > USD 500 million in DMD
alone, for combined US and EU markets • Novel gene therapy for congenital
with intention to own commercialization muscular dystrophy
• Additional regional commercial partnerings
21 Santhera Jan 1, 2021Santhera Pharmaceuticals
An emerging leader in neuromuscular diseases
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