Calliditas Therapeutics AB Stifel Healthcare Conference New York, - - PowerPoint PPT Presentation

Calliditas Therapeutics AB

Stifel Healthcare Conference New York, November 13, 2018 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 September 2018

Investment Overview 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) Design of upcoming 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 1 2 3 4 5 6 7

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September 2018 Calliditas Therapeutics

Development program is regulatory agreed and de-risked

Proteinuria – Accepted by FDA as surrogate marker for Phase 3 and accelerated approval… …supported with post-approval

• utcome data based on eGFR

→Clear strategy for the further development and approval of Nefecon from end of Phase 2b meetings →The first company to receive acceptance by the FDA to use proteinuria as Phase 3 endpoint for approval →Poised to become the first approve drug for broad use in the indication – safe, efficient and convenient. Only successful Phase 2b. →FDA and all major European countries have accepted Phase 3 design and protocol

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September 2018 Calliditas Therapeutics

Clinical advisory board comprising world leading IgAN specialists

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Calliditas Therapeutics September 2018

Prof Jonathan Barratt Nephrologist Leicester University, UK SELECTED EXPERIENCE:

• On the steering

committee of the International IgA Nephropathy Network

• Involved in many

clinical trials involving IgA nephropathy Prof Jürgen Floege Nephrologist Aachen University, Germany SELECTED EXPERIENCE:

• Executive council

member International Society of Nephrology and scientific advisory board of ERA/EDTA

• Responsible for the

STOP-IgAN study Prof Brad Rovin Nephrologist Ohio State University, USA SELECTED EXPERIENCE:

• Experienced

nephrologist working closely with Calliditas

• Focused on biomarker

development for glomerular diseases Prof Daniel Cattran Nephrologist University of Toronto, Canada SELECTED EXPERIENCE:

• Kidney Foundation of

Canada, PSI, the National Institutes of Health and the Canadian Institutes for Health Research Dr Hernan Trimarchi Nephrologist Universidad de Buenos Aires, Argentina SELECTED EXPERIENCE:

• Experienced

nephrologist

• Part of the global IgAN

steering committee Prof Bengt Fellström Nephrologist Akademiska sjukhuset, Sweden SELECTED EXPERIENCE:

• Senior professor at

Department of Medical Sciences

• Inventor of Nefecon

Prof Richard Lafayette Nephrologist Stanford University, USA SELECTED EXPERIENCE:

• Editor-in-Chief of ASN

Kidney News

• Member of the

Glomerular Disease Advisory Committee, ASN Prof Vladimir Tesar Nephrologist Charles University in Prague, Czech Republic SELECTED EXPERIENCE:

• Scientific Advisory

Board of ERA/EDTA and ASN

• Was responsible for

the VALIGA study

Broad support from key opinion leaders underpin global development program Global Advisory Board

Our lead indication: IgA nephropathy – large unmet medical need

PROFILE

ESTIMATED PREVALENCE

Genetic predisposition – not sufficient but

• necessary. Environmental, bacterial, dietary

triggers. Incidence estimated at 2.5 per 100,000 - For the US market corresponding to approximately 6,000- 7,000 new cases each year 130,000-150,000 200,000 ~2,100,000 ~190,000

MAIN MARKET POTENTIAL MARKET OPPORTUNITIES

Normally presents in the 20-30s – more prevalent in men than in women. Up to 50% at risk of ESRD within 10-20 years.

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September 2018 Calliditas Therapeutics

Implications of current off label approach

September 2018

7 Recent clinical studies show significant safety issues1,2

KOL reactions “Until less toxic therapies for IgAN are available, treatment with corticosteroids will need to be made in the context of conflicting evidence, and should likely be limited to patients at highest risk of disease progression who understand the significant risk of adverse events”

– Sean Barbour and John Feehally, Curr Opin Nephrol Hypertens 2017

The nephrology community is mindful that infection-related deaths have been

• bserved

in recent studies of patients with IgAN treated with corticosteroids, particularly in patients of Asian race with high-risk disease”

– Heather Reich, AJKD 2017

Source: 1) Lv et al (2017) JAMA 318(5):432-442. 2) Rauen et al (2015) NEJM 373(23):2225-2236

Calliditas Therapeutics

Disease origin and progression – predominant theory

September 2018

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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

Key properties of our lead candidate Nefecon

 Targeted local delivery of potent immunosuppressive agent to Peyer’s patches in the ileum  90% first pass liver metabolism  minimize systemic side effects  Substantially similar design to successful large Phase 2b study  significantly reduced development risk  Unique two-step release profile

─ PH-governed delayed disintegration of the capsule ─ Sustained but fast uptake throughout the Ileum

Comments Release profile of Nefecon 9

September 2018 Calliditas Therapeutics

Successful Phase 2b trial

September 2018

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

 Statistically significant UPCR reduction compared

to placebo - 9 months treatment (p=0.0066)

 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) indicating low systemic GCS exposure

 No severe infections and no mortality  Benign safety profile of 16 mg Nefecon typical for

low dose immune suppression

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Calliditas Therapeutics

Clinical Phase 3 study NEFIGARD to confirm Phase 2b results

Nefecon Phase 2b design

Run-in

3 months follow-up 9 months on treatment

Nefecon Phase 2b design Nefecon Phase 3 design – NEFIGARD

→Phase 3 study design replicates successful

Ph2b

→Only 200 versus previous 150 patients (Ph2b) →Fixed 16mg Nefecon once daily oral dose →Recognized surrogate marker for approval

Key highlights

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September 2018 Calliditas Therapeutics

Endpoint: Proteinuria reduction in IgAN patients

→Around 150 clinical sites in 19 countries →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 same as in Phase 2b - proteinuria reduction measured in the first 200 patients after

nine months of treatment – basis for the accelerated approval in the US / conditional approval in Europe

• Potential for full approval if proteinuria reduction is substantial, or based on results from interim analysis of

eGFR from the 450 completed patients, expected around 6 months after receiving accelerated approval

• Convenient, oral medication of well tolerated substance appropriate for broad population with potential for

disease modification – avoidance of dialysis / transplantation

• First patient randomized in November 2018

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Calliditas Therapeutics September 2018

Commercialization strategy for Nefecon

September 2018

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

 Focus on 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 nephrologists who treat IgA nephropathy patients, many of whom perform a hub and spoke function of expertise to surrounding clinics  Calliditas can effectively target identified group of nephrologists with a relatively small sales and marketing organization

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

ESRD causes considerable costs to society

September 2018

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

14 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

Strong product protection and product exclusivity

September 2018

Orphan designation Existing patents Patent strategy Soft barriers

 Granted orphan drug designation in the US and

• Europe. Potential data protection and market

exclusivity for 7 years (US) and 10 years (Europe)  Calliditas has been granted patents covering Nefecon, its formulation and method of manufacturing  The formulation patent runs until 2029  Strategic focus on the US and Europe with extension into other geographical markets  New MoU patent filed in April 2018, potential for additional filings to build patent estate  Significant formulation and manufacturing know-how  Questionable relevance of bioequivalence studies  Nefecon is the most advanced therapy in development

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Calliditas Therapeutics

Going forward: full focus on the Nefecon program

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 H2 2021

• NEFIGARD first

patient randomized

• Pediatric

investigational plan submitted to EMA

• Application for

ODD for second indication submitted

• FDA response

regarding regulatory path proposal for pipeline asset

• Publication of

new data from exploratory studies from Phase 2b in major scientific publication

• Approval of

ODD designation for second indication

• EMA decision

regarding pediatric pathway

• FDA / EMA

meetings regarding regulatory pathway for second indication

• Part A fully

recruited

• Top line data

200 patients

• Study fully

recruited

• Filing with

regulatory agencies

• Enrolment first

patient in treatment modality trials / label expansion

• Interim analysis

based on 450 patients

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September 2018 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) Design of upcoming 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 1 2 3 4 5 6 7

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September 2018 Calliditas Therapeutics

Q&A

Financial Calendar  Q4 report 2018 February 7, 2019 IR Contact Mikael Widell, Head of IR & Communications Email: mikael.widell@calliditas.com Telephone: +46 703 11 99 60

September 2018

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Calliditas Therapeutics