What Your CRO Doesn't Know Could Hurt You

1. What your cro doesn’t Know could hurt you How to leverage Canada for Study Expansion & Recruitment

2. Patient 001 – ADC This pa(ent was diagnosed with Mul(ple Myeloma in 2002. A pharmacist by training, he was highly educated and well aware of his chances for survival and the limited treatment op(ons that were available at the (me. He asked his oncologist about par(cipa(ng in a clinical trial but was informed there was only one available. He eagerly signed on, but was randomized to the control arm.

3. It’s stories like these that give meaning to what we do and why we are so passionate about our mission, which is to aDract cu$ng-‐edge oncology trials to Canada and to connect sponsors with a network of highly mo(vated inves(gators and their pa(ents. Scimega’s mission:

4. A Look Under The Hood of the Reverse Feasibility Program -‐ REB Strategy -‐ Site Contract Execu(on -‐ Regulatory Strategy Keys to AcceleraAng Site Performance Real-‐life Canadian Expansion Success Stories & Results summary

5. The Reverse Feasibility Program Est. 2008

6. What are investigators looking for? The ques(ons we seek to answer oMen revolve around how we can help aDract more oncology trials that would be successful in Canada. Selling the idea of a niche CRO that is 100% dedicated to oncology is not the hard part. Everyone can understand the value in that. The true challenge lies in how to sell Canada -‐ a region well known for its data quality, but not usually recognized for its speed. The key has been to understand what drives enrolment. In other words, to understand what inves(gators are looking for!

7. Why some trials just seem to run by themselves? ? Why some inves(gators just seem to “get the science” and grasp the urgency of one program but not another? ? To do so we need To understand: Meanwhile: Others just go through the mo(ons and don't seem very mo(vated…

8. sTEP 1a Con(nuous survey of Canadian inves(gator needs and interests We start by reaching out to our Reverse Feasibility Champions and asking them to provide us with their preferences in terms of compounds, indica(ons and lines of therapy. We do this on a regular basis.

9. Engagement and input from pa(ent advocacy groups sTEP 1b

10. 1csTEP Find U.S. biotech sponsors in need of oncology study expansion. Once we have an idea of what is needed, we ac(vely aDend key oncology events like AACR, ASCO and ASH in an eﬀort to meet with sponsors developing in the key indica(ons Canadian sites are in need of for their pa(ents.

11. 2sTEP Sponsor compounds/studies matched to needs of Canadian sites Once a match is found, we oﬀer to help the sponsor enhance their recruitment by expanding their trial to the right sites in Canada.

12. 3sTEP Approach select sites with summary of criteria We execute a mutual CDA with the sponsor and request that they allow us to use our CDA template to share info with the sites. Having been around since 1997 means the sites know, like and trust us. We help accelerate the process with the help of pre-‐approved templates.

13. 4sTEP Introduce sponsor to sites and discuss viability & feasibility Once we have conﬁrmed interest we coordinate a conference call with each Inves(gator so the sponsor can assess the sites’ level of engagement for themselves.

14. 5sTEP Iden(fy best ﬁt sites We typically iden(fy more sites than are required so the sponsor has the privilege of cherry-‐picking the best sites for their program.

15. 6sTEP Start-‐up & FPI (ﬁrst pa(ent-‐in) The proof is in the start-‐up and the Reverse Feasibility approach has resulted in start-‐up (mes that are rou(nely up to 50% faster than the industry average.

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17. Knowing investigators Isn’t enough What else drives Reverse Feasibility Performance?

18. REB Strategy sTart-up strategy Unlike centers in the U.S., Canadian ins(tu(ons do not have private Central Ethics Boards. Provincial review boards propose that sites iden(fy a “lead site” to coordinate with all other par(cipa(ng sites. As you can see by these ﬂowcharts it’s a complex process. That’s why it’s so cri(cal to have the right team on the ground to help you navigate the system and expedite start-‐up.

19. 21 Site Contract Strategy sTart-up strategy Scimega model Clinical Trial Agreement Process Our model CTA is US biotech friendly (addressing all key issues such as IP, indemnity, ownership and obliga(ons), and it has been nego(ated and approved with all the top cancer centers in Canada. This alleviates the administra(ve burden on the sites and removes the contract signing boDleneck, thereby expedi(ng start-‐up which leads to faster FSO and First Pa(ent In.

20. 22 sTart-up strategy Regulatory Strategy •  Parallel REB / Health Canada Review (Ame to prepare a CTA: 1-‐2 weeks) •  Having the right contacts at Health Canada (oﬃcial / unoﬃcial discussions) •  Knowing when to hold a pre-‐CTA meeAng and when to avoid it

21. Average Site Start-‐Up (me in Canada 36 weeks Scimega Site Start-‐Up (me using Reverse Feasibility 14 weeks » » Why do some trials take forever to start-‐up and then lag behind in recruitment, while other trials just seem to take oﬀ? We found that what truly mo(vates them is not a monetary incen(ve, but rather the chance to par(cipate in cuing-‐edge science, that has academic merit and publica(on opportuni(es.

22. Canadian Expansion Success Stories

23. Phase 1 dose ﬁnding HER2+ BrCa study looking at oral HER2 inhibitor in combina(on with T-‐DM1 Trial had been ongoing for 6 months at 7 sites in the U.S. Target end of recruitment by July 2015 cAse study 1 Situation:

24. challenge reason Action taken Slow Enrolment 0.1 pts/month Scarcity of comparator arm naïve subjects (comparator drug in wide use in US) 3x Repeat customer: Came to Canada aMer last study was completed 3 months ahead of schedule cAse study 1

25. Introduced Sponsor to select Reverse Feasibility Champions Conﬁrmed Inves(gator Interest (comparator arm approved but not yet covered for 2nd line) results Iden(ﬁed 5 sites in less than two weeks Selected 4 sites Average Start-‐Up: 14 weeks from CPS to SI Study closed to enrolment in April 2015 1 2 3 cAse study 1 START-UP METRICS 4

26. Enrolment Performance cAse study 1 SITES 33% Canada vs. 67% US Patients 55% Canada vs. 45% US CAN US CAN US

27. Thanks to the Reverse Feasibility Program and Scimega’s ability to aCract perEnent clinical trials to Canada, several of my paEents were able to LIVE signiﬁcantly longer.” Dr. Cristiano ferrario Montreal Jewish General hospital “2015 reverse feasibility champion”

28. cAse study 2 Situation: Sophis(cated Phase III Immuno-‐Oncology study in mRCC Global trial ongoing for 14 months Recruitment at risk Minimize logis(cal complexity

29. challenge reason Action taken cAse study 2 Slow Enrolment L o g i s ( c a l C o m p l e x i t y (required fresh tumor sample collec(on and access to leukapheresis lab) Site Expansion : Were told by exis(ng CRO that Europe was the op(on; not Canada due to lack of PI interest & sites with limited capabili(es

30. Introduced Sponsor to select Reverse Feasibility Champions Conﬁrmed Inves(gator Interest (comparator arm approved but not yet covered for 2nd line) results cAse study 2 Within 2 weeks we had conﬁrmed 6 sites Sponsor selected top 5 sites to add to exisAng four; In the end we doubled the # of sites in Canada Average Start-‐Up: 9.3 weeks from CPS to SIV 1 2 3 4 START-UP METRICS

31. Introduced Sponsor to select Reverse Feasibility Champions Conﬁrmed Inves(gator Interest (comparator arm approved but not yet covered for 2nd line) results cAse study 2 Scimega ExisAng CRO in Canada IRB TYPE Local Local # sites 5 4 Time from CPS – IRBapp 7.8 weeks 14.1 weeks Time from IRBapp – SIV 1.5 weeks total: 9.3 weeks 18.7 weeks total : 32.8 weeks START-UP METRICS

32. cAse study 2 Enrolment Performance

33. Scimega managed to expedite EC/IRB regulatory submissions at the site level, and did it much faster than our global CRO. They are nimble, aDen(ve and have an experienced oncology team that can handle all aspects of study opera(ons and site level needs” VP, Clinical and medical affairs

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35. disclaimer While some ini(al resistance from the exis(ng CROs is to be expected it is nice to see how fast their study teams mesh with ours and how quickly they appreciate that our success means the trial’s success, which ul(mately translates into their own success. NO U.S. CROs WERE HARMED DURING THE CONDUCT OF THESE TRIALS.

36. Mobilizing an expert canadian team significantly enhances study start-up & overall performance conclusion

37. UPDATE ON Patient 001 – ADC

38. PATIENT A.D.C ALDO DEL COL Since being diagnosed with Mul(ple Myeloma in 2002, Mr. Del Col co-‐founded Myeloma Canada, the only non-‐profit organiza(on uniquely focused on the needs of the Canadian myeloma community. Myeloma Canada works with regional support groups, key myeloma experts and other pa(ent organiza(ons. Their Scien(fic Advisory Board brings together Canada’s leading myeloma inves(gators and clinicians and is the founda(on of the Myeloma Canada Research Network (MCRN), a myeloma study group that ac(vated its first clinical trial early in 2012.

39. WHAT OUR CLIENTS ARE SAYING

What Your CRO Doesn't Know Could Hurt You

Roberto Lara

What Your CRO Doesn't Know Could Hurt You