Simbec-Orion Case Study: Rare & Orphan, Respiratory Disease

CASE STUDY THERAPY AREA: RARE & ORPHAN, RESPIRATORY DISEASE EFFICIENT PROJECT & DATA MANAGEMENT SOLUTIONS DRIVE COMPLETION OF CONCEPT STUDY FOR RARE DISEASE, AHEAD OF PLANNED TIMELINES.

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CASE STUDY A RANDOMISED, DOUBLE BLIND, MULTI CENTRE, PLACEBO CONTROLLED DOSE ESCALATION STUDY IN HEALTHY SUBJECTS INVESTIGATING THE SAFETY, TOLERABILITY AND PHARMACOKINETIC PROPERTIES OF THE STUDY DRUG, FOLLOWED BY AN EXPANSION COHORT TREATING SUBJECTS WITH IDIOPATHIC PULMONARY FIBROSIS (IPF)

SPONSOR OBJECTIVES: The biotech Sponsor needed to report on the safety and tolerability of the lead molecule, as well as direct target engagement and biomarker effects for IPF.

PATIENT PROFILE: Part 1 – Healthy male volunteers Part 2 – Male and female patients with IPF • Male patients or female patients of non childbearing potential with adequate organ function and a clinical diagnosis consistent with IPF •

Aged between 45 and 85 years with a forced vital capacity (FVC) ≥ 45% predicted and a forced expiratory volume in one second (FEV1)/FVC ratio ≥ 0.7, oxygen saturation > 90% by pulse oximetry while breathing ambient air at rest and a diffusing capacity of lungs for carbon monoxide (DLCO) > 25%

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Patients who were able to undergo bronchoalveolar lavage (BAL)

DRUG TYPE Galectin-3 Inhibitor, Inhaled.

STUDY OBJECTIVES: •

SAD study to evaluate the safety and tolerability in healthy male subjects.

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To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of the study drug when administered as a single dose to healthy male subjects.

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To evaluate the safety and tolerability of multiple doses of the study drug in male and female patients of non childbearing potential with IPF.

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To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of the study drug when administered in multiple doses to male and female patients of non childbearing potential with IPF. Page 1 of 2

CASE STUDY STUDY CHALLENGES: IPF is a unmet medical need affecting between 200,000 – 300,000 patients in the Western world. The strict study inclusion and exclusion criteria meant that patient recruitment would be challenging. Many IPF patients were not able to be enrolled, due to the severity of their condition.

Patients not only had to meet study criteria but also had to produce a suitable FEV value to be considered for study inclusion.

Patients were admitted to the hospital sites on D1, D7 and D14, to be given the study drug for home dosing, prior to PK sampling at the hospital. Training on inhaler use to ensure optimal results was also critical to success.

OUR SOLUTIONS: Additional sites were pre-identified and set-up for inclusion in the study. Their inclusion was dependent on patient enrolment rates at other sites.

Whilst the healthy volunteer part of the study was in progress and completed in eight months, the start up and the identification of IPF patients was able to begin in parallel.

As patients were so difficult to recruit, centralised project management by a project manager (PM) located in the region was crucial to help motivate sites and communicate progress. The PM also needed to work closely with data management to ensure the entire project was kept on track.

As patients progressed on the study, Simbec-Orion data management and the PM were able to communicate efficiently because they were based on the same site. This enabled tasks to be split, operated in parallel and reviewed continuously to avoid delay.

In turn, the monitor worked with site staff to pre-empt potential discrepancies and have them resolved immediately, rather than waiting for specific timepoints.

Teamwork mitigated the risk of slow recruitment and Simbec-Orion was able to speed up the delivery of data management activities to compensate time.

The efficient, centralised set-up of the Simbec-Orion project and management teams stripped out much of the delay associated with the increased bureaucracy, complexity, and disparate geography of teams, hierarchies, and processes at larger CROs. Training was conducted by the CRA on the use of the inhaler for patient dosing, which ensured consistent dosing and use of the inhaler between both healthy volunteer and patient study populations.

RESULT FOR CUSTOMER: Simbec-Orion was able to identify the risk of slow recruitment early and then work to mitigate these risks, resulting in delivery of the final CSR ahead of time. The Sponsor has been able to report positive results on the safety and tolerability in IPF patients.

The Sponsor is now in a position to source investment to develop the compound further, or to licence the compound.

Number of countries:

01 (UK)

Number of sites:

05

Number of enrolled subjects:

36 24 36 x HEALTHY VOLUNTEERS

x IPF PATIENTS

Timelines FSI to Final Study Report:

24 MONTHS

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MISSION STATEMENT We are Simbec-Orion. An international, full service, boutique CRO; growing by bringing together the best possible people, healthcare professionals and drug developers, from all areas of clinical development.

We focus on a defined series of core therapeutic areas, where we can make best use of our skills elegantly to design, execute and deliver our clients’ clinical development needs.

We are making Simbec-Orion a highly respected and profitable boutique CRO. We do this by working for our clients with excellence, commitment and passion for our trade. We provide an environment in which our colleagues can continue to grow and develop.

We will always remember that our work leads to the improvement of patients’ lives

To find out how Simbec-Orion can help with your clinical development program email info@SimbecOrion.com Or call our business development team on +44 1753 578080 FRONT COVER: CREDITED TO: YALE ROSEN HARD METAL LUNG DISEASE/GIANT CELL INTERSTITIAL PNEUMONIA (GIP) - CASE 259

UNDER CREATIVE COMMONS LICENSING WWW.CREATIVECOMMONS.ORG/LICENSES/BY-SA/2.0/

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