My Experience in the PROTECT-1 Study

1. My Experience in the PROTECT-1 Study MUDr. Compeľ Vladimír

2. Dear colleagues, It is a great honour for me to participate in today´s proceedings of the conference. I appreciate your invitation a lot. It is a pleasure for me to get a chance to meet the ChemoCentryx staff who support the development of a high quality and high efficiency medicament treating Crohn disease.

3. Study Center Personnel Principal Investigator: MUDr. V. CompeľVladimír Sub-Investigator: MUDr.Procházka Bohumil Study Coordinator: PharmDr. Lobotková Miriam

4. Study Location Private Gastroenterology Centre Senovazne namesti 1616 370 01 České Budějovice Czech Republic

5. Study Statistics • Study site was initiated on 20 April 2007 • Eleven patients have been screened to date • The first patient was randomized on 11 May 2007 • Six patients have been enrolled so far into the Induction Period • Three patients have been enrolled into the Maintenance Period • Five patients have failed screening because of low CRP

6. 0.97 1 0.75 0.5 Monthly Recruitment Rate 0.28 0.25 0 Compel All Sites Enrollment Rate Compared to Other Study Sites

7. My Experience in the PROTECT-1 Study I have been asked to present our experiences acquired within the process of treating patients suffering from Crohn disease in the beginning of our studies and to give away our secrets. We all know well the work is demanding, the choosing of patients complicated inclusion and exclusion criteria limiting I myself am convinced that we do not have any secrets but you may be interested in our system of working with the patient.

8. My Experience in the PROTECT-1 Study In each patient we usually start with the standard initial interview, besides, -each patient gets informed about the disease and treatment - each patient gets informed about the follow up visits -each patient gets informed about the prognosis -each patient is provided with printed information materials. In the process of endoscopy and ultrasound examination the patient is being informed about the scope of the disease both verbally and visually (he or she is able to follow the process of examination accompanied by our commentary). I am convinced that the information process as described above presents an integral component of services provided generally.

9. My Experience in the PROTECT-1 Study The following slides should stress the fact that the ultrasound examination of Crohn disease of patients should be carried out under a friendly and amicable atmosphere, that a patient – doctor relationship based on mutual trust and co-operation should be established. The patient will appreciate thorough information concerning the exact place of action of the medication administered within the study.

10. It is obvious that Crohn disease affects all layers of the intestine wall. In accordance with the scope of affliction of the individual layers the disease can be monitored, as ….. an acute, subacute or chronic condition The ultrasound examination can detect and monitor various complications or responses within the surrounding areas – especially in messentery, nodes, abscesses, invagination, fistulae, stenoses, prestenotic dilatations of the intestine etc.

11. Due to the fact that the patient is encouraged to follow the ultrasound monitor, he or she is interested in -what his or her intestine wall looks like, -how thick it is, -how it gets supplied with blood, -whether nodes around the afflicted intestine detected in the previous examination are visible etc…. In this way the patient gets fully engaged into his or her disease, during each visit the patient can follow the development of the disorder, the results of treatment, regime mistakes, worsening of the condition etc….

12. The same principles are applied during the initial interview with the patient when we usually (in compliance with the printed patient information materials provided by ChemoCentryx Inc.) -stress the place of effect of the new medicament -in this case = the submucosa of the intestine wall -lymphocytes in the submucosa with their inflammatory activity and production mediators of inflammation -lymphocytes with the described CCR9 receptors which are blocked by the medicament Thus, we are able to achieve a better compliance with the applied study medicament. We have no other secrets.

13. The next slides will show the terminal ileum afflicted by Crohn disease in a female patient participating in the study, including the development of changes when treated by CCX282-B (the original medication stayed unchanged).

14. Normal wall of caecum The wall thickeness here amounts to 1.2mm The afflicted terminal ileum (the wall 4-8mm Somewhere here there will be Bauh.valve

15. I explain to my patients - here your Crohn disease is well visible - here your immunity cells are concentrated („disoriented lymfocytes“) which produce pro-inflammatory mediators

16. Chronic appearance of the submucosa Subacute appearance of the submucosa (well blood-supplied submucosa …i.e.an intensive infiltration by immunity cells)

17. the length of the affected terminal ileum section (here approximately 7cm = 3,6 plus 3,3cm)

18. Before CCX282-B therapy July 24, 2007 • - the thickness of the wall amounts to 8 mm • the submucosa has oedematous character • - doppler suggests a high blood supply to the area • And besides, an inflammatory – hyperechogeneous messentery can be observed

19. During CCX282-B therapy 17.sep.2007 - the thickness of the terminal ileum has decreased - the blood supply of the wall has decreased - the submucosa swelling has decreased .. i.e.the infiltration of the terminal ileum by further immunity cells has decseased

20. the thickness of the termilnal ileum wall in its individual segments does not exceed 0,9 ... 2,4 … 2,8mm.

21. During CCX282-B therapy 17.sep.2007 It is obvious that when the patient has the chance to see these changes he or she is pleased both by the improved condition and the medication. As a result, his or her compliance with the new drug has increased.

22. … Thanks for your atention …