Calliditas Therapeutics AB Stockholm, June 2019 Rene - - PowerPoint PPT Presentation

Calliditas Therapeutics AB

Stockholm, June 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

• ccurrence 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.

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Calliditas Therapeutics March 2019

A specialty pharmaceutical company based in Stockholm, Sweden Listed on Nasdaq in Sweden in June 2018 – Midcap segment (ticker CALTX) Market cap June 2019: 180 MUSD Cash position end Q1, 2019: 63 MUSD Top 5 Shareholders: Industrifonden, Investinor, B Julander, Gladiator, AFA Insurance Ongoing Phase 3 read out expected for IgAN in 2H 2020; Pipeline: ODD received for AIH and PBC

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March 2019 Calliditas Therapeutics

Investment Summary Calliditas

Novel treatment of IgA nephropathy (IgAN) with potential disease modifying effect Clear path to market – FDA acceptance of proteinuria as surrogate marker Mode of action targets the origin of the disease – active in the gut Only successful placebo controlled, randomized Ph2b study in IgA nephropathy (150 patients) The ongoing clinical Phase 3 study NEFIGARD replicates Phase 2b Additional potential for pipeline development, in-licensing targeting orphan disease Significant unmet medical need with USD 1bn market opportunity, no approved drugs

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March 2019 Calliditas Therapeutics

Our lead indication: IgA nephropathy – large unmet medical need

PROFILE

ESTIMATED PREVALENCE

Genetic predisposition – required but not

• sufficient. Environmental, bacterial, dietary

triggers. Normally presents in the 20-30s – more prevalent in men than in women. 130,000-150,000 200,000 ~2,100,000 ~190,000

MAIN MARKET POTENTIAL MARKET OPPORTUNITIES

Up to 50% at risk of ESRD within 10-20 years.

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March 2019 Calliditas Therapeutics

Disease origin and progression – predominant theory

March 2019

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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.

Calliditas Therapeutics

IgA nephropathy Cluster complexes Immune response Sugar deficient IgA Peyer´s patches 1 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

Nefecon offers local treatment at origin of disease

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 Active substance is budesonide  90% first pass liver metabolism  minimize systemic side effects  Designed to provide a locally restricted and highly concentrated release of budesonide to the Peyer’s patches for maximum effect  Targeted local delivery of potent immunosuppressive agent to Peyer’s patches in the ileum  Unique two-step release profile

─ PH-governed delayed disintegration of the capsule ─ Pulse like exposure throughout the Ileum

Drug product based on known active ingredient Unique targeted release profile

Budesonide concentration

March 2019 Company Presentation

Successful Phase 2b trial

March 2019

Primary endpoint: Reduction in proteinuria

2.7%

• 27.3%
• 21.5%

Placebo Nefecon (16 mg) Nefecon (8 mg) % ∆ UPCR

Large study population – 150 patients Randomized, double-blinded, placebo controlled

• 9.8%

0.6%

• 0.9%

Placebo Nefecon (16 mg) Nefecon (8 mg) % ∆ eGFR

Secondary endpoint: Stabilization of eGFR

Oral dose taken daily over a nine- month period European study in 62 sites in 10 countries

P (16mg)=0.0026 P (8mg) = 0.0064 P (16mg)<0.01 P (8mg)<0.03

Only Phase 2b Study in IgAN to reach Primary Endpoint

Conclusion – Efficacious and safe drug profile

Efficacy

 Phase 2b trial of 150 patients demonstrated

clinically relevant reduction in proteinuria and GFR stabilization in the treatment arms

 UPCR reduction compared to placebo - 9

months treatment (p=0.0066)

 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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Calliditas Therapeutics

Clinical Phase 3 study NEFIGARD to confirm Phase 2b results

Nefecon Phase 2b design

Run-in

9 months on treatment

Nefecon Phase 2b design Nefecon Phase 3 design – NEFIGARD

→Phase 3 study design replicates successful

Ph2b

→200 versus previous 150 patients (Ph2b) →16mg Nefecon once daily oral dose →Surrogate marker; Proteinuria for market

approval

Key highlights

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March 2019 Calliditas Therapeutics

Endpoint: Proteinuria reduction in IgAN patients

→Around 150 clinical sites in 19 countries →Up to 450 patients in total →Read out on first 200 patients basis for approval and US market launch →Top line read-

• ut estimated

H2 2020 →Endpoint: Proteinuria reduction for approval of Phase 3 study…

→…with eGFR in

post approval follow up

• Endpoint for Phase 3 study identical to endpoint for Phase 2b: Proteinuria reduction.
• Measured in the first 200 patients after nine months of oral treatment – basis for the accelerated approval in

the US / conditional approval in Europe

• Potential for full approval if proteinuria reduction is substantial, or on basis of planned interim analysis in post

approval observational study. Data on kidney function expected around 18 months from top line read out

• Convenient, oral medication for broad population with disease modifying potential – avoidance of dialysis
• FPI in November 2018
• Company sponsored statistical framework, Inker et al 2016, basis for FDA surrogate marker acceptance

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Calliditas Therapeutics March 2019

ESRD causes considerable costs to society

March 2019

Cost of dialysis USD 89,000 USD 70,000-200,000

Average annual cost per person in the US

Hemodialysis treatment in 20131 Based on payer's interviews 20162

Total estimated annual hemodialysis cost in the US of USD 42 billion1 11 Cost of transplantation USD 414,800

Average cost per kidney transplant

Total invoiced fees per transplantation3

Total estimated annual kidney transplantation cost of in the USA of USD 7 billion

Source: 1) U.S. Renal Data System, USRDS 2013 Annual Data Report: Atlas of End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2014. 2) Calliditas estimate based on interviews commissioned by the Company. 3) Milliman, Milliman research report:2017 U.S organ and tissue and transplant cost estimation and discussion.

Calliditas Therapeutics

Commercialization strategy for Nefecon

March 2019

Calliditas believes that IgA nephropathy represents a market opportunity of USD 1bn or more in the US Rights

 Maintain all rights to Nefecon in the US in all indications

Commercial strategy

 Company managed US commercialization  Assess partnerships in EU and RoW  Target IgA nephropathy patients at risk of progressing to ESRD (up to 50%)  Earlier stage treatment to prevent progression and preserve kidney function  Focus on clinics providing treatment of IgAN patients - Hub and spoke structure  Targeting of identified group of nephrologists with a relatively small sales and marketing organization  Collaborate with patient organizations

General commercial strategy US commercialization strategy Rationale for US commercialization

 Significant unmet medical need  Desire for early stage and safer treatments  Sizeable socioeconomic benefits  Orphan drug  Specialist target market  Disease modifying potential

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Calliditas Therapeutics

Strong product protection and product exclusivity

March 2019

Orphan designation Existing patents Patent strategy Soft barriers

 Granted orphan drug designation in the US and

• Europe. Data protection and market exclusivity for

7 years and 10 years, respectively  Granted patents covering Nefecon, its formulation and method of manufacturing - runs until 2029  Strategic focus on the US and Europe with extension into other geographical markets  New patent estate initiated in 2018  Significant formulation and manufacturing know- how  Bioequivalence studies would require adaptation

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Calliditas Therapeutics

Pipeline Indications - Autoimmune Hepatitis (AIH)

March 2019 Corporate Presentation

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Source: 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

 A rare, orphan, chronic inflammation of the liver  The cause is unknown  Leads at variable rates to cirrhosis with complications like portal hypertension, liver failure and liver cancer  Typical symptoms are fatigue, abdominal discomfort, jaundice, enlarged liver, skin rashes, joint pains and in women, loss of menstruation

Standard of care

 Currently no products approved in the US / care 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, or approximately 25,000 patients

Estimated prevalence

50,000 – 80,000 Annual US incidence 0.1 – 1.9 per 100,000

Primary Biliary Cholangitis (PBC)

November 2017 Analyst presentation

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Source: 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  Early symptoms include fatigue, itchy skin and dry eyes/mouth. Later stages - liver stiffness, musculoskeletal pain, edema, jaundice and underactive thyroid

Standard of care

 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 indicates 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

Out-licensing of Nefecon to Greater China

November 2017 Analyst presentation

16 The Market

 IgA Nephropathy is more common in China than in Europe

• r the US, and is cited in publications as being the most

common reason for ESRD.  According to a large Chinese epidemiology study1 on over 13,000 renal biopsies, IgAN represented over 30%.  A convenient, oral medication to control the disease with the potential of avoiding ESRD is particularly attractive in a China, taking into account travelling distance to hospitals etc.

The Deal

 Partnering with Everest Medicines, a well funded, private biopharma company with highly experienced staff predominantly with big pharma backgrounds. Have a broad pipeline of late stage clinical programs for China  Total deal value of $121m, with $15m in 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

Source: 1) Am J Nephrol 2009;30:268-273

Going forward: focus on Nefecon program & Pipeline

H1 2018

• Filing of new

patent application related to Nefecon

Ongoing updates regarding commercial strategy and plans

H2 2018 H1 2019 H2 2019 H1 2020 H2 2020 H1 2021 H1 2022

• NEFIGARD

first patient in

• Application

for ODD for second indication submitted

• Application

for ODD for third indication submitted

• Filing of

Pediatric Investigation al Plan submitted to EMA

• Approval of

ODD designation for second indication

• Approval of

ODD designation for third indication

• EMA meeting

to discuss surrogate marker

• FDA meeting

regarding regulatory pathway for second indication

• 200 patients

recruited

• Clinical trial

for pipe line indication initiated subject to FDA guidance

• EMA decision

regarding pediatric pathway

• Top line read
• ut for 200

patients

• Study fully

recruited

• Filing with

regulatory agencies for market approval

• Enrolment

first patient in treatment modality trials / label expansion

• Interim

analysis based on 450 patients for validation of surrogate marker

• Commercial

launch of Nefecon

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March 2019 Corporate Presentation

Investment Summary Calliditas

Novel treatment of IgA nephropathy (IgAN) with potential disease modifying effect Clear path to market – FDA acceptance of proteinuria as surrogate marker Mode of action targets the origin of the disease – active in the gut Only successful placebo controlled, randomized Ph2b study in IgA nephropathy (150 patients) The ongoing clinical Phase 3 study NEFIGARD replicates Phase 2b Additional potential for pipeline development, in-licensing targeting orphan disease Significant unmet medical need with USD 1bn market opportunity, no approved drugs

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March 2019 Calliditas Therapeutics