calliditas therapeutics ab · with no approved drugs . us annual market ... near term approval path...
TRANSCRIPT
Calliditas Therapeutics AB
Pareto Securities Health Care Conference 2019September 5, 2019
Renée Aguiar-Lucander, CEO
Disclaimer
Important information
This presentation may contain certain forward-looking statements and opinions. Forward-looking statements are statements that do not relate to historical facts and events and such statements and opinions pertaining to the future that, by example, contain wording such as “believes”, “estimates”, “anticipates”, “expects”, “assumes”, “forecasts”, “intends”, “could”, “will”, “should”, “would”, “according to estimates”, “is of the opinion”, “may”, “plans”, “potential”, “predicts”, “projects”, “to the knowledge of” or similar expressions, which are intended to identify a statement as forward-looking. This applies, in particular, to statements and opinions in this presentation concerning the future financial returns, plans and expectations with respect to the business and management of Calliditas Therapeutics, future growth and profitability and general economic and regulatory environment and other matters affecting Calliditas Therapeutics. Forward-looking statements are based on current estimates and assumptions made according to the best of Calliditas Therapeutics’ knowledge. Such forward-looking statements are subject to risks, uncertainties, and other factors that could cause the actual results, including Calliditas Therapeutics’ cash flow, financial condition and results of operations, to differ materially from the results, or fail to meet expectations expressly or implicitly assumed or described in those statements or to turn out to be less favorable than the results expressly or implicitly assumed or described in those statements. Accordingly, prospective investors and other third parties should not place undue reliance on the forward-looking statements herein. Calliditas Therapeutics can give no assurance regarding the future accuracy of the opinions set forth herein or as to the actual occurrence of any predicted developments. In light of the risks, uncertainties and assumptions associated with forward-looking statements, it is possible that the future events mentioned in this presentation may not occur. Moreover, the forward-looking estimates and forecasts derived from third-party studies referred to in the presentation may prove to be inaccurate. Actual results, performance or events may differ materially from those in such statements due to, without limitation, changes in general economic conditions, in particular economic conditions in the markets on which Calliditas Therapeutics operates, changes affecting interest rate levels, changes affecting currency exchange rates, changes in competition levels and changes in laws and regulations. The information, opinions and forward-looking statements contained in this announcement speak only as at its date, and are subject to change without notice.
2Calliditas Therapeutics September 2019
Out licensing deal for China ($121m) closed in Q2, validating market potential in IgAN for Nefecon
Nasdaq Stockholm listed (ticker CALTX) specialty pharmaceutical company (market cap SEK 2.2bn)
Cash position end Q2 2019: $56m (SEK 534m)
Key shareholders include: Industrifonden, B.V.F, B Julander, Gladiator, AFA Insurance
NefIgArd pivotal Phase 3 study in IgAN on plan, expected readout in H2 2020
3Calliditas Therapeutics September 2019
$121m (SEK 1.1bn) out licensing deal for Greater China validates future commercial potential
Investment Summary Calliditas
Novel treatment of IgA nephropathy (IgAN) with potential disease modifying effect targeting the origin of the disease
Strong cash position fully finances ongoing clinical development portfolio
Ongoing pivotal clinical Phase 3 study NefIgArd replicates successful Phase 2b
Additional potential for pipeline development: orphan liver indications and targeted in-licensing
Significant unmet medical need with no approved drugs. US annual market opportunity of around $2bn. Combined opportunity in China and Europe of at least equal size.
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4September 2019Calliditas Therapeutics
Our lead indication: IgA nephropathy – large unmet medical need
PROFILE ESTIMATED PREVALENCE
Genetic predisposition – required but not sufficientEnvironmental, bacterial, dietary triggers
Normally diagnosed in ages 20-30sMore prevalent in men than in womenUp to 50% at risk of ESRD within 10-20 years
130,000-150,000
200,000
600,000-800,000
MAI
N M
ARKE
TS5
March 2019
Calliditas Therapeutics September 2019
Wordwide Nefecon Market Potential3
ESRD causes considerable costs to society• Average annual cost per person in the US
$70,000-$200,0001
• Average cost per kidney transplant $414,8002 $4bn
ESTIMATED DIAGNOSED PATIENTS
Source: 1) Calliditas estimate based on third party research commissioned by the Company. 2) Milliman, Milliman research report:2017 U.S organ and tissue and transplant cost estimation and discussion. 3) 50% of patients diagnosed being candidates for treatment & recent third party (IQVIA) research commissioned by the Company
Disease origin and progression – predominant theory
September 2018Calliditas Therapeutics 6
IgA nephropathyCluster complexesImmune responseSugar deficient IgAPeyer’s patches1 2 3 4
In patients there is an increase in a subclass of immunoglobulin molecules (“IgA”) which lack a specific sugar modification
The sugar-deficient IgA molecules trigger an immune response resulting in formation of antibody clusters
As the clusters enter the circulation, they form even larger complexes that eventually lodge in the kidneys
Deposits of immune complexes result in inflammation, necrosis and destruction of the kidneys’ filtration apparatus
Lymphoid tissue; Peyer’s patches in the distal part of the small intestines produces IgA antibodies
Source: Suzuki et al, J Am Soc Nephrol 2011;22(10):1795-803; Novak et al, Curr Opin Nephrol Hypertens 2013; 22(3):287-94; Novak et al, Kidney Dis (Basel). 2015; 1(1):8-18.
Nefecon offers local treatment at origin of disease
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Designed to provide a locally restricted and highly concentrated release of budesonide to Peyer’s patches for maximum effect
16mg oral dose
Unique two-step release profile
PH-governed delayed disintegration of the capsule
Pulse-like exposure throughout the iIeum
Unique targeted release profile
September 2019Calliditas Therapeutics
Nefecon offers local treatment at origin of disease
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Oral, once daily administration
Budesonide – proven to be safe and effective
Minimize systemic side effects 90% first pass liver metabolism
Orphan protection in the US and the EU
Strong product protection for Nefecon
10 years market exclusivity in the EU
7 years market exclusivity in the US
Formulation patent 2029 expiry
Drug product based on known active ingredient
September 2019Company Presentation
Triple coated beads for sustained release
Polymer coatingSeal coatingActive coatingCore particle
Enteric coat for delayed release
Capsule
Successful Phase 2b trial
Primary endpoint: Reduction in proteinuria
2.7%
-27.3%-21.5%
Placebo Nefecon(16 mg)
Nefecon(8 mg)
% ∆
UP
CR
-9.8%
0.6%
-0.9%
Placebo Nefecon(16 mg)
Nefecon(8 mg)
% ∆
eG
FR
Secondary endpoint:Stabilization of eGFR
P (16mg)=0.0026P (8mg) = 0.0064
P (16mg)<0.01P (8mg)<0.03
Only placebo controlled, randomized Phase 2b Study in IgANto reach Primary Endpoint and show renal protection Conclusion – Efficacious and safe drug profile
Efficacy Pan European; 150 patients, 10 countries, 62 sites Highly statistically significant UPCR (proteinuria)
reduction compared to placebo - 9 months treatment (p=0.0066)
Highly statistically significant eGFR stabilization compared to placebo – 9 months treatment (p=0.0026)
Safety and tolerability Medication-related adverse effects were transient
and mainly mild (77%) to moderate (22%) No metabolic adverse events (hypertension,
diabetes, weight gain) No severe infections Benign safety profile of 16 mg Nefecon
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-4,7 ml/min/1.73m2
Calliditas Therapeutics September 2019Study results published in The Lancet, 2017
Ongoing clinical Phase 3 study NefIgArd to confirm Phase 2b results
9 months on treatment
Nefecon Phase 3 design – NefIgArd
→ Phase 3 study design replicates successful Ph2b
→ Fixed 16mg Nefecon once daily oral dose
→ Reduction of proteinuria: Accelerated approval/market access
→ Full approval on 2 year eGFR based endpoint – 360 patients
Key highlights
10Calliditas Therapeutics September 2019
Topline readout: 200 patients
Nefecon – Poised to be first approved treatment of IgAN
→FPI Nov 2018 →140 clinical sites
recruiting in 19 countries
→Top line read-out on first 200 patients estimated H2 2020
→Filing with regulatory agencies for accelerated / conditional approval Q1 2021
→ Market launch Q1 2022
→ Readout for full approval mid 2022
11Calliditas Therapeutics September 2019
• Company sponsored statistical framework, Inker et al 2016, basis for FDA surrogate marker acceptance
• Potential for full approval based on proteinuria, if reduction is substantial, however 505b2 pathway assumed
• Read out on loss of kidney function over two years (eGFR) for validation of surrogate marker H2 2022
2018 2019 2020 2021 2022
Additional open chronic dosing study with Nefecon
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Preliminary Outline:
Global study with around 100 patients Leveraging existing sites and networks Inclusion criteria different from ongoing study Focus: safety and stabilization of eGFR Provide additional support for disease modification
Planned start in Q1 2020 Duration 12-18 months depending on feedback from health authorities Starting dose 16mg, step down to maintenance dose
Enables additional data capture related to safety & maintenance treatment
Calliditas Therapeutics September 2019
Commercialization strategy for IgAN in the US
March 2019
Commercial strategy Target IgA nephropathy patients at risk of
progressing to ESRD (up to 50%)
Earlier stage treatment to prevent progression and preserve kidney function
Chronic / intermittent dosing
Targeting of therapeutically focused nephrologists - hub and spoke structure
Collaborate with patient organizations
Need for relatively small sales and marketing organization
Company managed US commercialization
Significant unmet medical need
Calliditas Therapeutics September 2019 13
Calliditas TherapeuticsMarket opportunity Annual market opportunity over $2bn
Indicative pricing from market
research $55,000-85,000 per treatment cycle1
Positioning Backbone treatment potential - first approved medication for IgAN
Severe side effects of existing off label treatments
Orphan drug
Specialist target market
Disease modifying potential –delay or avoid dialysis / transplantation
Source: 1 Third party (IQVIA) research commissioned by the Company
Out-licensing of Nefecon to Greater China
14Calliditas Therapeutics September 2019
Partnering deal with Everest Medicines
Well funded, highly experienced biopharma company with a broad pipeline of late stage clinical programs for China
Total deal value of $121m, with $15m upfront payment
Everest Medicines responsible for the development and commercialization in the territory
Potential to be the first approved medication for IgAN in China, targeting a significant unmet medical need
Market opportunity
Greater China has a population of approx. 1.4bn people, which implies that the total IgAN population is very sizeable
Assuming that biopsies have been carried out fairly regularly for at least the last 10 years, it would indicate a diagnosed population today of around 600,000 – 800,000
As biopsies are still limited to large hospitals, the actual patient population should be significantly larger, likely at least 2x
Source: 1) Am J Nephrol 2009;30:268-273
Commercialization strategy for IgAN in EU and China
March 2019
Commercial strategy
One, or several commercial partners Orphan status in the EU Market landscape mapping work
initiated to assess potential
Partnership signed in June 2019 with Everest Medicines
Potential to join global NefIgArd trial Near term approval path for Chinese
market
Partner driven commercialization
Calliditas Therapeutics September 2019 15
Market opportunity
~$1bn
Indicative pricing To be provided post results from market study
Positioning Potential to be first approved treatment for IgAN – backbone treatment
Partner driven commercialization
~$1bn
Partner assessment
Partner assessment
Calliditas Pipeline
Calliditas Therapeutics September 2019 16
(As per September 1, 2019)
Candidate IndicationResearch/Preclinical Phase 1 Phase 2 Phase 3 Market Approval / phase 4
Completed
Nefecon IgA Nephropathy
- Chronic dosing
- Roll over study, intermittent treatment
- Transplant study
- Single course
Agreed /Ongoing
Planned
Primary Biliary Cholangitis
Autoimmune HepatitisPartner Asset1
1 In-licensed from Dr. Falk Pharma
Pipeline Indications - Autoimmune Hepatitis (AIH)
September 2019Corporate Presentation 17Source: 1) Feld et al, Hepatology 2005;42:53-62, Sahebjam and Vierling, Front Med. 2015 Jun;9(2):187-219. 2) Sahebjam and Vierling, Front Med 2015; 9(2):187-219. 3) Czaja, Expert Opin Drug Saf. 2008;7(3):319-33; Czaja, Liver Int 2009;29(6):816-23; Manns et al, Hepatology 2010;51(6):2193-213 (AASLD 2010 AIH Guideline).
The disease
Rare, orphan, chronic inflammation of the liver with unknown cause
Leads at variable rates to cirrhosis with complications like portal hypertension, liver failure and liver cancer
Medical need
Estimated prevalence
60,000 – 80,000
Annual US incidence 0.1 – 1.9
per 100,000
Currently no products approved in the US: SoC treatment includes immunosuppression with systemic steroids (prednisone) alone or in combination with azathioprine
Up to 80% of treated patients report steroid related side effects after 2 years and 15% discontinue due to drug related adverse events
Calliditas estimates the intolerance and relapse segments together comprise 35-40% of the total population, approx. 25,000 patients
Calliditas’ strategic in-licensing for AIH
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In-licensing agreement with Dr. Falk Pharma for US market
Maximizes opportunity to accelerate time to approval and US market access in AIH Creates optionality and flexibility for product portfolio in the US Orphan indication with market exclusivity and reimbursement No approved treatments €1.5m upfront payment, total deal value of €40m
Preparation for FDA interaction initiated FDA interaction planned for Q1 2020
Calliditas Therapeutics September 2019
Pipeline Indications - Primary Biliary Cholangitis (PBC)
Calliditas Therapeutics September 2019 19Source: 1) Lindor et al, Hepatology. 2009 Jul;50(1):291-308,EASL PBC Clinical Practice Gudielines, Journal of Hepatology 2017; 67:145–172. 2) Nguyen et al, Best Pract Res Clin Gastroenterol 2010; 24(5): 647–654. 3) Kim et al, Gastroenterology 2000;119:1631–1636). 4) EASL PBC Clinical Practice Gudielines, Journal of Hepatology 2017; 67:145–172. 5) Company estimate based on prevalence reported by Kim et al Gastroenterology 2000; 119(6):1631-6. 6) Company estimate based on prevalence reported by Kim et al Gastroenterology 2000; 119(6):1631-6 and Nguyen et al, Best Pract Res Clin Gastroenterol 2010; 24(5):647-54.
The disease
A progressive chronic autoimmune disease of the liver
The bile ducts are destroyed by inflammatory processes, bile accumulates in the liver causing an increase in the liver volume (cholestasis)
If untreated, the active liver tissue is destroyed and replaced by fibrous tissue, cirrhosis and liver transplant
Medical need
Ursodeoxycholic acid (UDCA) and obeticholic acid (Ocaliva) are the only FDA-approved medical treatments for PBC3
No targeted anti-inflammatory therapy is registered in the US or Europe
Previous trials indicate that corticosteroids may alleviate symptoms and improve biochemical and histologic findings4
Estimated prevalence
140,0005
Annual US incidence 0.3 – 5.8
per 100,0002
Primary Biliary Cholangitis competition
Calliditas Therapeutics September 2019
Standard of careUDCA
Nefecontargeted budesonide
FXR agonistsOCALIVA (Intercept)
Cilofexor (P2, Gilead)*Tropifexor (Novartis)*
EDP305 (P2, Enanta)**
Anti-fibroticsAldafermin (P2, NGM Biopharma)*
Setanaxib (P2, Genkyotex)*
PPAR agonistsBezafibrate (P3, Acad*; Intercept)
Elafibranor (P2, Genfit)*Seladelpar (P3, Cymabay)**
Saroglitazar (P2, Zydus Cadila)***
Primary BiliaryCholangitis
* Completed. ** Primary completion 2020. *** Primary completion 2019Public sources
Unique position addressing local autoimmune reactions
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Going forward: focus on Nefecon program & project pipeline
H1 2018
• IPO raising $82m on Nasdaq OMX
Ongoing updates regarding commercial strategy and plans
H2 2018 H1 2019 H2 2019 H1 2020 H2 2020 2021 2022
• NEFIGARD first patient in
• Application for ODD for second indication submitted
• Application for ODD for third indication submitted
• Filing of Pediatric Investigational Plan submitted to EMA
• Approval of ODD designation for second indication
• Approval of ODD designation for third indication
• EMA meeting to discuss surrogate marker
• 200 patients recruited
• In-licensing of additional product
• Out-licensing of major territory rights
• FDA interaction enhancing Part B design
• Clinical trial initiation of chronic dosing study with Nefecon
• EMA decision regarding pediatric pathway
• FDA meeting regarding regulatory pathway for AIH indication
• Initiation of roll-over study for re-treatment
• Top line read out for 200 patients
• Study fully recruited
• Initiation of roll-over study
• Filing with regulatory agencies for market approval
• Open study results of chronic / repeat dosing trials
• Commercial launch of Nefecon in H1
• Analysis based on 360 patients for validation of surrogate marker around mid 2022
21September 2019Calliditas Therapeutics
Strong cash position fully finances ongoing clinical development
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Cash position $56m (SEK 534m) end of Q2
Additional $21.5m (SEK 210m) raised in Q3, attracting specialist US investor California-based BVF Capital Partners L.P. took a significant position Incremental funds enable initiation of additional study with Nefecon
$15m (SEK 140m) paid from China deal in Q3
Financed well beyond NDA filing
Ability to pursue additional Phase 3 supporting trials, as well as pursue attractive in-licensing options selectively
Calliditas Therapeutics September 2019
$121m (SEK 1.1bn) out licensing deal for Greater China validates future commercial potential
Investment Summary Calliditas
Novel treatment of IgA nephropathy (IgAN) with potential disease modifying effect targeting the origin of the disease
Strong cash position fully finances ongoing clinical development portfolio
Ongoing pivotal clinical Phase 3 study NefIgArd replicates successful Phase 2b
Additional potential for pipeline development: orphan liver indications and targeted in-licensing
Significant unmet medical need with no approved drugs. US annual market opportunity of around $2bn. Combined opportunity in China and Europe of at least equal size.
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23September 2019Calliditas Therapeutics