Rome, 15th December 2015 Daniela Bassi Corporate Product Manager Understanding SURVET Rome, 15th December 2015 Daniela Bassi Corporate Product Manager

Do we clearly know SURVET and re-DVT indication?

The Background Patients with a first episode of unprovoked venous thromboembolism have a high risk of recurrence after discontinuation of anticoagulant therapy. Extending anticoagulation reduces the risk of recurrence but is associated with increased bleeding

Unprovoked When it occurred in the absence of any know risk factors for this event Unknown origin VTE patients have a two-fold higher rate of recurrent VTE than the patients with acquired, transient risk factors!

High risk of recurrence ~20% within 2 years ~50% within 10 years This does not change depending on whether anticoagulation is prolonged for 6, 12, or 24 months!!

Discontinuation or Extending Low-moderate bleeding risk Extended AC over 3 months High bleeding risk Stop AC at 3 months ACCP 2012 - Duration of AC in patients with a first unprovoked VTE AC should be given for not < 3 months

In practice, how to choose? The decision as to go on or discontinue AC after the first 3 months is individually tailored and balanced Risk of recurrence Risk of bleeding Patients preference must also be taken into consideration!

Which are the eligible situations of use for Sulodexide?

And after 3 months, what happen? It depends on the “balance” INITIAL AC from 0 to ~7 days risk of re-VTE > risk of bleeding Heparin or LMWHs or Fondaparinux or NOACs (rivaroxaban, dabigatran, apixaban, edoxaban) LONG-TERM AC from ~7 days to ~3 months risk of re-VTE > risk of bleeding VTKs (warfarin, acenocoumarol) or NOACs (rivaroxaban, dabigatran, apixaban, edoxaban) And after 3 months, what happen?

from ~3 months to indefinite Scenario #1 re-VTE Risk > Bleeding Risk EXTENDED AC from ~3 months to indefinite VTKs (warfarin, acenocoumarol) or NOACs (rivaroxaban, dabigatran, apixaban, edoxaban) Only in case, the patient refuses AC therapy!

Scenario #2 Low- moderate re-VTE Risk not supportive for a continuation of AC treatment …but who prefer to have a protection with an effective & safe therapy Sulodexide may be used in patients with a risk level that does not require continuation of AC treatment but show an acceptable risk (<5%) to select a protective therapy, with lower bleeding risk.

from 3 / indefinite to indefinite Scenario #3 Bleeding risk > re-VTE risk All the situation in which the risk of bleeding and the related possible damage are bigger than the risk of recurrence. EXTENDED AC from 3 / indefinite to indefinite VTKs (warfarin, acenocoumarol)* or NOACs (rivaroxaban, dabigatran, apixaban, edoxaban)*  Aspirin or Sulodexide (capsules) CRITERIA FOR EXTENDED AC: more documented VTE episodes; Active cancer; Serious thrombophilia; Antiphospholid antibody syndrome; PE with shock or life-threatening; > systolic PAP; Other indications for AC; NYHA 3 or 4

with existing comorbidities Some specific cases Elderly ≥75 years and/or with existing comorbidities Elderly patients have an increased risk of bleeding and hepatic and renal complications when using anticoagulant treatment and are also likely to have more comorbidities – possible drug–drug interactions must be considered Sulodexide can be used in this population as it is not associated with an increased bleeding risk, has no known drug interactions, and does not affect renal function

Can we consider NOACs in our reference market ?

Remember that…. NOACs market has a huge dimension More than 50% of NOACs prescriptions are in atrial fibrillation The situation of use are not exactly the same as Sulodexide

Who is in charge of the VTE patient management?

Initiation of treatment We need to know…. First visit Diagnosis Initiation of treatment Follow-up Who? The management of patients with VTE appeared to be very complex and it vary somewhat between countries

Which target are involved? Vascular Surgeon GP Any Other? Cardiologist Hematologist Angiologist

Which are the key messages from the study?

NO increased risk of bleeding The main strengths NO increased risk of bleeding No episodes of major bleeding within 2 years in either treatment group!

The main strengths TOLERABILITY

… and what about the posology? Higher dosage 4 cps/day Long term treatment 2 years The results are guarantee only with this treatment scheme!

Last but not least….

Corporate Activities and Materials

SURVET Project Overview ADVOCACY N.2 Advisory Board KOLs/Investigators Kick Off Meeting 22 Oct 2015 International AB 25 Nov 2015 1 2 2015 MEDIATION Stand Alone International Meeting KOLs/Investigators/Local Influencers Launch Event 12-13 April 2015 3 2016 DISSEMINATION (International Congresses/ Local Launch events/ Advisory Boards) International/ Local Meetings 4

Phases 1-2: Advocacy STEERING COMMITTEE Giuseppe Maria ANDREOZZI Angelo BIGNAMINI Giovanni DAVÍ Gualtiero PALARETI 1 Kick Off Meeting 22 Oct 2015 ADVISORS Andrej DŽUPINA (Slovakia) Grzegorz MADYCKI (Poland) Carlos MAGALHÃES MOURA (Portugal) Jiří MATUŠKA (Czech Republic) German SOKURENKO (Russia) Adriana VISONÀ (Italy) 2 International AB 25 Nov 2015 KEY POINTS DISCUSSED The SURVET study: expert advice on the results and their implications for the use of sulodexide in the prevention of VTE recurrence The ideal patient types who would most benefit from extended treatment with sulodexide in the prevention of VTE recurrence National perspectives on the study results, SURVET survey and types of patients suitable for Sulodexide

Specialists Phase 3: Launch Event To whom is addressed? 12-13 April 2015 Specialists Local KOLs / Influencers that will spread the SURVET Trial results To whom is addressed?

Local tool ready for use The Objectives Disclose the SURVET results and clinical implication Discuss new therapeutic perspective vs current treatment options Provide clear guidance in the identification of target patients Prepare delegates to become speakers in their own country In long term, create a KOLs network who can help to enrich the international dialogue on the prevention and treatment of VTE Each delegate will receive a post-deliverable resource kit Local tool ready for use

Phase 4: Dissemination European Congress of Phlebology 13-17 April 2016 Rome, IT International/ Local Meetings 4 European Venous Forum 07-09 July 2016 London, UK World Congress of IUA 05-09 October 2016 Lyon, FR

SURVET Corporate Materials Reprint Folder Visual aid Slide Kit

Do we clearly know SURVET and re-DVT indication?