Str e n g t h e n i n g S i te R e lati o n s h i p s Th r o u g h R e v e r se Fe a si b i l i t y -

Why so many US oncology drug developers have enhanced their clinical trial performance by leveraging Canada for successful study expansion.

It could be a friend, colleague or family member.

We all know at least one person, be it a friend, colleague or family member, that has been diagnosed with some form of cancer. This news becomes even harder to accept for those unable to access cutting-

edge compounds that could potentially extend their lives, because they are being developed and tested elsewhere in North America.

It’s situations like these that give meaning to what we do and why we are so passionate about our mission, which is to attract cutting-edge trials to Canada and to connect sponsors with a network of highly motivated investigators and their patients.

Scimega’s mission:

How the Reverse Feasibility Program was born & why it works? Real-life Canadian Expansion Success Stories & Results Dr. Stephen Welch - Canadian Investigator: A Reverse Feasibility Champion.

Contents

What are investigators looking for?

The questions we seek to answer often revolve around how we can help attract 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 investigators are looking for!

Others just go through the motions and don't seem very motivated… Why some trials just seem to run

by themselves?

?

Why some investigators just seem to “get the science” and grasp the urgency of one program but not another?

?

To do so we need To understand:

Meanwhile:

Next we needed to understand:

What drive site performance? Why do some trials take forever to start-up and then lag behind in recruitment, while other trials just seem to take off?

We asked ourselves these questions and decided to reach out to a few investigators with whom we had privileged relationships and discovered that, like everybody else on the planet, they have their own needs and wants – things

they are passionate about. We found that what truly motivates them is not a monetary incentive, but rather the chance to participate in cutting-edge science, that has academic merit and publication opportunities.

and so just like that...

Average Site Start-Up time in Canada

36 weeks

»

Average Site Start-Up time using Reverse Feasibility

12-15 weeks »

The Reverse Feasibility Program was born

2008

www.reversefeasibility.com

The Reverse Feasibility Program is Scimega's collaborative network of Canada's top performing medical oncologists that routinely share their academic interests and trial needs in an effort to assist us in promoting Canada's oncology clinical research capabilities.

Continuous survey of Canadian investigator 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, indications and lines of therapy. We do this on a regular basis.

sTEP 1a

Preliminary results Here are some preliminary results from our most recent Investigator Survey that will be published in a quarterly report to showcase the indications and lines of therapy that would be very successful in Canada today.

# of Sites

Phase 1 trials Interested

1st line Non-Small Cell Lung Cancer (NSCLC) Acute Myelogenous Leukemia (AML) Small Cell Lung Cancer (SCLC) Acute Lymphocytic Leukemia (ALL) Colon Cancer Gastric Cancer Malignant Mesothelioma Melanoma Stomach (Gastric) Cancer Bladder Cancer Renal Cell Carcinoma (RCC) Triple Negative Breast Cancer

7 6 6 5 5 5 5 5 5 4 4 4

10

Non-Small Cell Lung Cancer (NSCLC) Acute Myelogenous Leukemia (AML) Colon Cancer Small Cell Lung Cancer (SCLC) Gastric Cancer Melanoma Acute Lymphocytic Leukemia (ALL) Stomach (Gastric) Cancer Renal Cell Carcinoma (RCC) Breast HER2 Gastrointestinal Stromal Tumors (GIST)

6 6 6 5 5 5 4 4 4 4 4

# of Sites 2nd line

Find U.S. biotech sponsors in need of oncology study expansion. Once we have an idea of what is needed, we actively attend key oncology events like AACR, ASCO and ASH in an effort to meet with sponsors developing in the key indications Canadian sites are in need of for their patients.

sTEP 1b

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.

2 sTEP

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.

3 sTEP

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

4 sTEP

Identify best fit sites We typically identify more sites than are required so the sponsor has the privilege of cherry-picking the best sites for their program.

5 sTEP

Start-up & FPI (first patient-in) The proof is in the start-up and the Reverse Feasibility approach has resulted in start-up times that are routinely up to 50% faster than the industry average.

6 sTEP

Canadian Expansion

Success Stories

Phase I/II study looking at a novel pathway inhibitor in combination with an EGFR inhibitor in CRC. Trial had been ongoing for 7 months at 13 sites in the U.S. The sponsor had an aggressive target for end of recruitment

cAse study 1

Situation:

challenge reason Action taken prior to RFPr

Slow Enrolment (0.18) pts/month

Scarcity of treatment naïve subjects

(comparator drug was in wide use in the US)

Hired well-known SMO to no avail

cAse study 1

Introduced Sponsor to select Reverse Feasibility Champions Confirmed Investigator Interest (NB: Comparator arm was approved in Canada but not yet covered for 2nd line)

results

48-hours later we had confirmed five (5) sites 2-weeks later we had 11 sites to choose from Sponsor selected the top eight

1

2

1

2

3

cAse study 1 REVERSE FEASIBILITY APPROACH

Active case study:

S ta r t- u p m e t r i c s

Phase I/II, 8 sites; CRC Population; Mutational Analysis

Academic IRB TYPE Hospital Central

# sites 4 4

Time from CPS to IRBapp 11.3 weeks

Time from IRBapp – SIV 1st site in 6 days 3 weeks

ENROLLMENT (pts/site/mo)

Scimega Actual = 0.42

Prior to RFPr = 0.18

cAse study 1

E n r o l m e n t c u r v e cAse study 1

0

5

10

15

20

25

30

Num

ber o

f pat

ient

s

Sponsor's Target Enrolment Actual Enrolment

EOS (end of study) was completed 3 months ahead of schedule

an additional program awarded for expansion: Q1-14 : Phase I dose finding Her2+ BrCa pts

• Identified 5 sites in less than two weeks • Kept 4 • Avg start-up ;15-weeks CPS-SIV • Recruited 55% of pts with 33% of sites

1

Sponsors must carefully weigh the cost of supplying comparator drugs against the potential cost of time-to-market delay due to prolonged enrollment. ... we found that Canadian investigators were highly engaged in our studies and that their participation helped to significantly improve our enrollment times.”

VP, Clinical Operations – U.S. Biotech

Sophisticated Phase III Immuno-Oncology study in mRCC Global trial ongoing for 14 months Recruitment at risk Minimize logistical complexity

Situation:

cAse study 2

challenge reason Action taken prior to RFPr

Slow Enrolment Logistical Complexity (requires fresh tumor

sample collection and access to leukapheresis lab)

1 Hiring of Regional MSLs 2 Financial support for sites/patients

cAse study 2

Site Expansion : Were told by existing CRO that Europe was the option; not Canada due to lack of PI interest & sites with limited capabilities

REVERSE FEASIBILITY APPROACH

Introduced Sponsor to select Reverse Feasibility Champions Confirmed Investigator Interest

results

48-hours later had confirmed two sites

Then 6 more

Sponsor selected top five sites to add to existing four;

In the end we doubled the # of sites in Canada

1

2

1 2 3 4

cAse study 2

Scimega

Existing CRO in Canada

IRB TYPE Local Local

# sites 5 4

Time from IRBsub – 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

Active case study: Phase III, 9 sites; mRCC Population; Immunotherapy

cAse study 2 S ta r t- u p m e t r i c s C o m p a r i n g P E R F O R M A N C E O F E x i s t i n g C R O T O R F P r

Having a TRUSTED PARTNER IN CANADA helped us tap into high performing INVESTIGATIVE sites. ...They worked closely with us and HAVE delivered on everything we expected.”

global director, scientific affairs

Phase II study of a novel pathway inhibitor in combination with an ALK inhibitor in ALK+ NSCLC Trial had been ongoing for 19 months in U.S. and Western Europe Extensive delays were made worse by introduction of competing 2nd and 3rd Gen Inhibitors into the clinic Target end of recruitment - July 2015

Situation:

cAse study 3

challenge reason Action taken prior to RFPr

Slow Enrolment (scarcity of patient

population)

Protocol restrictions Competition with 2nd and 3rd Generation inhibitors Rare patient population

++ Protocol amendments Study criteria changed to allow patients that have received new gen inhibitors Expand the # of sites:

existing CRO reported ZERO opportunity (no PI interest)

cAse study 3

Introduced Sponsor to select Reverse Feasibility Champions Confirmed Investigator Interest

results

72-hours later we had confirmed three sites

2 weeks later we had five

Where there were none… we found five

1

2

1 2 3

cAse study 3 REVERSE FEASIBILITY APPROACH

Active case study:

S ta r t- u p m e t r i c s

Phase I/II, 5 sites; ALK+ NSCLC Population

Academic IRB TYPE Local

Time from CPS to SIV 18.7 weeks*

*Note: 1. Start-up activities during summer

Enrolment Have met every study milestones (FSI, ASI, FPI, ½TPI)

cAse study 3

Additional program has since been awarded for expansion: Q1-15 : Phase II Hematologic Malignancy –

• After months of “searching” existing CRO reported ZERO interest in Canada

• Scimega added four (4) sites in less than two weeks;

EOS (end of study) set to be completed 1 month ahead of schedule

cAse study 3

Subscribe to our blog to follow the progress of this ongoing clinical trial.

http://www.scimega.com/blog

disclaimer

While some initial resistance from the existing 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 ultimately translates into their own success.

NO U.S. CROs WERE HARMED DURING THE CONDUCT OF THESE TRIALS.

And now a word from Dr. Stephen Welch, a Canadian Investigator & Reverse Feasibility Champion from the Regional Cancer Center in London, Ontario.

Mobilizing AN expert Canadian team significantly enhances study start-up and OVERALL

performance

conclusion

WHAT OUR CLIENTS ARE SAYING

To di scu s s yo u r o n c o l o gy cli n i c a l tr i a l e xpa n si o n n e e ds Contact us

Roberto Lara Director of Business Development (450) 629-2200 ext. 226 rlara@scimega.com

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