Active Biotech AB
Safe Harbor Statement
Certain statements made during the course of this presentation are forward-looking statements. Such forward-looking statements involve known and unknown risks, uncertainties and other important factors that could cause the actual results, performance or achievements of the company, or industry results, to differ materially from any future results, performance or achievement implied by such forward-looking statements.
Statements made during the course of this presentation that are forward-looking are based on the company’s current beliefs regarding a large number of factors affecting its business. There can be no assurance that (i) the company has correctly measured or identified all of the factors affecting its business or the extent of their likely impact, (ii) the available information with respect to these factors on which the Company’s analysis is based is complete or accurate, (iii) the company’s analysis is correct or (iv) the Company’s strategy, which is based in part on this analysis, will be successful.
All forward-looking statements speak only as of the date of this presentation or, in the case of any document incorporated by reference, the date of that document. All subsequent written and oral forward-looking statements attributable to the company or any person acting on the company's behalf are qualified by this cautionary statement. The company does not undertake any obligation to update or publicly release any revisions to forward-looking statements to reflect events,
3 3
• Swedish Biotechnology Company
• Core competence in Autoimmune/Inflammatory
diseases and Cancer
• Spin out from Pharmacia 1998
• Listed company NASDAQ OMX Nordic: ACTI
• Share price SEK 71.25 (10.80 USD), market cap
SEK 5.3 B (809 MUSD) as of January 8, 2014
• A total of 60 employees
5 5
Ref: Compston A, Coles A. Lancet. 2002;359:1221-1231.
MS pathology and disease progression
Frequent inflammation, demyelination, axonal transection, plasticity, and remyelination Infrequent inflammation, chronic axonal degeneration, gliosis
Relapsing-Remitting Secondary Progression
Clinical Disability Clinical Threshold Brain Volume Inflammation Axonal Loss Continuing inflammation, persistent demyelination
Current Multiple Sclerosis Treatment Landscape
Injectable Oral Immunosuppressant • Lemtrada • Daclizumab (PIII) • Tysabri • Gilenya • Aubagio (Teriflunomide) Immunomodulator • Copaxone • Interferons • Plegridy (PEG-interferon) • Laquinimod (PIII) • Tecfidera (BG-12)Drugs on the market and in Phase III development
7
Laquinimod for the treatment of MS
• Oral, once-daily CNS-active disease-modifying treatment for MS
• Delaying disability progression (34.2%*), reducing flares (21.4%*) and brain atrophy (30%*)
• Safe for long term use
• A committed and established partner in Teva
• An extensive, ongoing clinical development program
Multiple sclerosis
• EU market application (MAA) for the treatment of RRMS submitted in July 2012
• CONCERTO - a third Phase III study ongoing under a SPA
- Two doses (0.6mg and 1.2mg) in approx. 1,800 RRMS patients for up to 24 months will be evaluated
- Primary endpoint confirmed disability progression as measured by the Expanded Disability Status Scale (EDSS)
• LIBRETTO - Phase III study in RRMS (0.6 and 1.2 mg). Primary endpoint brain
atrophy
Laquinimod clinical development
Other indications
• Further clinical development in Crohn’s disease and Lupus nephritis planned
for 2014
• Clinical studies in Huntington’s disease and Primary Progressive Multiple
9 9 9
Teva Pharmaceutical Industries
• Teva has global exclusive rights to develop, register, manufacture and
commercialize laquinimod since 2004
• Teva conducts and funds further clinical development of drug
• Expected to generate USD 92 million in overall milestones whereof
USD 22 million received so far
• Active Biotech to receive tiered double digit royalties on future sales - 15 year royalty period on country-by-country basis
- Higher royalty level in the Nordic/Baltic territory
Laquinimod Commercial Development and
Marketing Agreement
Prostate cancer
Increasing disease progression
2-4 years Median survival 25-30 months
• Over 400,000 new prostate cancer patients diagnosed annually
• Prostate cancer market 2013E; 7 BUSD1)
1) Credit Suisse Oct 2013 Surgery/radiation
Diagnosis Hormonal treatment
(approx. 50% of patients) Wait for progression Pre-chemo Taxotere + Pred. Post-chemo Local PC Metastatic CRPC Injectable Oral Targeting AR • Zytiga • Xtandi • Orteronel (PIII) Non-AR • Prostvac (PIII)
• Yervoy (PIII) • Provenge • Custirsen (PIII) • Jevtana • Xofigo (alpharadin) • Tasquinimod (PIII) • Cabozantinib (PIII)
Tasquinimod - a new first-in-class oral
anti-cancer therapy
Tasquinimod, potentially a new therapeutic option for chemo naïve patients with metastatic CRPC
A unique MoA targeting the tumor’s microenvironment, mainly by binding the S100A9 protein
12 12 12 Results • 69 % of tasquinimod patients vs 34 % of placebo patients
had not progressed at 6 months (p<0.0001) 1).
• Median Progression Free Survival 7.6 vs 3.3 months (p=0.0042)
• OS data2) supports that the
observed increase in PFS will translate into an increased OS in a trial with sufficient statistical power
Tasquinimod: Treating castrate resistant
prostate cancer (CRPC)
Placebo switch on tasquinimod
Phase II
• Disease progression: bone scan or CT scan, cancer pain, pathological event
• 206 asymptomatic metastatic CRPC patients in the US, Canada and Sweden
• 2:1 randomization 1.0 mg tasquinimod vs placebo
13 13 13
Indication: Metastatic castrate resistant prostate cancer (mCRPC) pre-chemo
Primary endpoint: Radiographic Progression Free Survival (rPFS) Key secondary endpoint: Overall survival (OS)
Study design: Randomized, double-blind placebo-controlled Regions: Global including US/Canada, Europe & China No. of patients: 1,245
Study status: Patient recruitment completed Dec 2012
Estimated filing: 2015
Coordinating
investigator: Michael A. Carducci, Johns Hopkins University, Baltimore, US
Ongoing Tasquinimod Phase III Trial
Surgery/radiation
Diagnosis Hormonal treatment
(approx. 50% of patients) Wait for progression Pre-chemo Taxotere + Pred. Post-chemo Local PC Metastatic CRPC
Tasquinimod Phase III Analysis plan
•
Primary radiographic progression-free survival (rPFS) analysis 2014
- at the same time as the first interim overall survival (OS) analysis
•
Time point for the OS interim analysis will be driven by the number
of OS events
15 15 15
Prostate cancer
• Phase II proof of concept clinical study (“Switch maintenance”) of
tasquinimod as maintenance therapy in patients with mCRPC who have not progressed after a first line docetaxel based chemotherapy (Ipsen)
• Phase I investigator sponsored clinical trial, led by Dr. Andrew
Armstrong at Duke University Hospital, US ( Tasquinimod and Jevtana)
Other cancers
• Phase IIa study with tasquinimod in metastatic renal, hepatic, ovarian
and gastric cancer (Ipsen)
Tasquinimod Further Clinical Development
Surgery/radiation
Diagnosis Hormonal treatment
(approx. 50% of patients) Wait for progression Pre-chemo Taxotere + Pred. Post-chemo Local PC Metastatic CRPC Ph III Ph II Ph I
Tasquinimod Co-development with Ipsen
• Partnership announced April 18, 2011
• Up to 200 M€, including 25 M€ upfront and 32 M€ milestones received so
far, and additional payments (upon achievement of clinical, regulatory and commercial milestones)
• Ipsen will pay Active Biotech progressive double-digit royalties on its net sales
• Active Biotech will be responsible for and finance the ongoing phase III trial
• Active Biotech granted Ipsen exclusive rights to commercialize tasquinimod
worldwide, except for North and South America and Japan where Active Biotech retains all commercial and marketing rights
17
Renal Cell Carcinoma (RCC)
•
180,000 new cases annually
1)•
RCC market 2011 – USD 2.7 billion
2)1) Cowen Therapeutic Categories Outlook March 2010 2) EvaluatePharma March 2012 Diagnosis Surgery Approx. 50% cured Therapy Disease progression Metastases approx. 50% of patients 5-year survival 5-15 %
ANYARA
• Selective drug retention in tumor tissue
• Activation and targeting of effector T cells
• Direct and indirect tumor cell killing
Therapeutic principle: SEA/E-120 CL VL5T4(V18) CH VH5T4(V14) SEA/E-120 CL VL5T4(V18) CH VH5T4(V14) ANYARA
Superantigen Anti-5T4 Fab
T lymphocyte Tumor cell
TCR 5T4 ANYARA TNF- IFN- Direct killing by CTL
T lymphocyte Tumor cell
TCR 5T4 ANYARA TNF- IFN- Direct killing by CTL
19
Number of patients 513
Randomization IFN vs ANYARA+IFN
Countries UK, Ru, Uk, Bu, Ro (50 sites) Primary endpoint Overall survival
• From Phase I to Phase II/III powered for OS analysis in RCC
• Primary endpoint not reached
• Subgroup analysis demonstrated proof of concept
• Doubling of PFS and OS in 25% of patients
• Good safety profile, in line with previous observations; most common adverse
events were grade 1-2 fever, nausea or vomiting
• Future development strategies to be discussed with regulatory authorities
• Based on these data, the goal is to sign a partnership for the continued
development of this unique, targeted, immune therapy
ANYARA: Phase II/III trial in RCC
Phase II/III Subgroup Analysis
• The 25 % of patients with low/normal levels of the biomarker IL-6 at
baseline and expected anti-superantigen antibody levels, showed a statistically significant treatment advantage on both OS and PFS
IL-6normal/low Anti-SAgexpected Baseline Anti-SAg Ba seline IL-6 Median Median 20
• OS for the ANYARA group 63.3 months vs
31.1 months for interferon-α, (p=0.02, HR=0.59)
• PFS 13.7 vs 5.8 months (p=0.016, HR=0.62)
• The subgroup accounts for 40-50% of the total number of advanced RCC
21 21 21
• Orphan indication - 1 to 3 per 10,000 in the US & EU
• Chronic autoimmune disease of unknown cause
• Fibrosis and vascular abnormalities affecting the skin, subcutaneous tissue,
muscles and internal organs such as gastrointestinal tract, lungs, heart and kidneys
• Clinically heterogeneous; autoantibody production, fibrosis and vascular damage
• Current treatment aimed at controlling symptoms and preventing complications
Systemic sclerosis (SSc)
Paquinimod (57-57): Oral Treatment of SSc
• Quinoline molecule previously in clinical development for treatment of SLE
• Orphan Medicinal Product status for the treatment of SSc granted in the EU
• Exploratory clinical study in SSc concluded: - 9 patients
- safety
- evaluate effects on disease related biomarkers
22
The ISI (“Inhibition of S100 Interactions”)
Project
Background
• Quinolines bind S100A9 (PLoS Biology April 2009)
• S100A9 interacts with the pro-inflammatory RAGE and TLR4 receptors
• Inhibition of S100A9/TLR4 interactions delays tumor growth (PLoS ONE March
2012)
The ISI Project
• First indication oncology
• Development of NCE’s that target S100 protein interactions
• Patent applications filed
• First CD selection 2014 = compound OFF ON = RAGE = TLR4 = S100
Financials January – September 2013
F.Y. F.Y.
2013 2012 2012 2013 2012 2012
Net sales 111.9 136.4 227.9 17.0 20.7 34.5
Operating loss -128.6 -168.7 -163.2 -19.5 -25.6 -24.7 Loss after tax -130.0 -175.1 -175.0 -19.7 -26.5 -26.5
Cash on hand at end of September, 2013: MSEK 322.2 (48.8 MUSD)
- not including 104.1 MSEK (15.8 MUSD) milestone payment from Ipsen paid in Oct, 2013
SEK/USD: 6.60
Jan - Sep Jan - Sep
25 25 25
Share information
Active Biotech market cap (Jan 8, 2014) SEK 5.3 billion
USD 809 million
Number of shares: 74.9 million
Major shareholders (December 30, 2014) MGA Holding 19 392 963 25.9% Nordstjernan 9 850 829 13.2% Investor 6 000 000 8.0% 3rd AP fund 2 633 556 3.5% Avanza Pension 1 863 128 2.5% JP Morgan Bank 1 362 501 1.8% Client Long 1 346 326 1.8% All other 32 474 279 43.3% Total 74 923 582 100.0% Ownership categories Swedish owners 81.1% Foreign owners 18.9% Number of shareholders 10 632 whereof 10 largest 61.0% whereof 20 largest 69.0%
Important value drivers 2014
•
CHMP scientific opinion on laquinimod in RRMS
•
Initiation of further clinical development with laquinimod in
Crohn's and/or Lupus Nephritis
•
Unblinding of tasquinimod Phase III study in prostate
cancer
28
Laquinimod clinical profile
• No signal for immunosuppression or Linomide®-related toxicity
• Elevations of liver enzymes, mostly asymptomatic, without signs of liver insufficiency
• Results from long-term study support a favorable safety and tolerability profile and suggest robust benefit in terms of early treatment (AAN, March 2013) 28
Effect size vs. Placebo (nominal p-value)
ALLEGRO BRAVO* INTEGRATED
ANALYSIS
Laq vs. PBO Laq vs. PBO Laq vs. PBO
Relapse Rate 23% (0.0024) 21% (0.03) 21.4% (0.0005) Disability (3m CDP) 36% (0.0122) 33.5% (0.04) 34.2% (0.0017) Brain Atrophy 32.8% (< 0.0001) 27.4% (0.0001) 30% (< 0.0001)
Cum # GdE T1 lesions 37%
(0.0003)
22% (0.062)
30% (0.0001)
Cum # new T2 lesions 30%
(0.0002)
19% (0.037)
24.2% (< 0.0001)