Cayman Pharma Neratovice, Czech Republic

Cayman Pharma s.r.o. Site Layout

NORTH

C5500 warehouse

B5170

C549A

C5490

History of CP Operations

• 1978 - Prostaglandin development was initiated in Spolana with

Chemical Institute of Technology in Prague

• 1979 - (±)-Cloprostenol production launched

• 1990 - Human PGs, Alprostadil, and Dinoprostone launched

• 1993, 1996, 2000, 2003, 2011, 2014 - FDA audits

• 2002 - NeraPharm established as an independently operating

subsidiary of Spolana

• 2006 – Acquisition of Cayman Pharma s.r.o. by Cayman Chemical

• 2007 - Production of Epoprostenol launched

• 2008 - Production of Travoprost launched

• 2009 – Production of Latanoprost launched

• 2012 – Production of Entecavir launched

• 2014 - Technology transfer of Bimatoprost from CC

Senior Management Senior Management Team

• Frank Cox, PhD – V.P. Global GMP Operations, 28 years of

experience in the Pharmaceutical Industry

• Ing. Petra Miketová, MBA, PhD - Managing Director, 20+ years of

experience in pharmaceutical field

• Ing. Jana Hartmanová –Director of Quality, Master of Chemistry,

20 + years of experience in pharmaceutical industry

• Ing. Jan Velík– Operations Director, Master of Chemistry,

20 + years of experience in fine chemicals and API production

• Jiřina Lidová – Commercial Director, Graduated specialist, 30+

years of experience in sales and marketing

• Ladislava Tintěrová – Finance Director, Graduate economist, 30+

years of experience in a financial management, accounting, and

controlling

• Jan Pavlík, PhD – R & D Director, Doctor of Pharmacy

10+ years of experience in chemical and biochemical synthesis

Key Competencies- Cayman Pharma s.r.o.

• API production under cGMP conditions

• Research and development of prostaglandin substances

and specialty chemicals

• Custom chemical synthesis

• Cooperation with end-user in registration procedure

• Scaling-up of production

• Validation and qualification of processes and facilities

• Development and validation of analytical methods

Cayman Pharma APIs Portfolio

Cayman Pharma APIs Portfolio

Quality Management System

• Quality System was developed in compliance with the

Act on Pharmaceuticals No. 378/2007 Coll.

• GMP system based on requirements stated in Decree

No. 411/2004 Coll., ICH Q7, CFR 21 and further

guidelines EMEA / FDA

• System subjected to regular audits

• Part of Integrated Management System (IMS);

certification according to ISO norms

Integrated Management System (IMS)

QMS (Quality Management System) ISO 9001:2008

EMS (Environmental Management System) ISO

14001:2004

SMS (Safety Management System) OHS&S 18001:2007

• QMS was certified in 2004 and extended in 2007, 2010

and 2013.

• IMS certificate was granted by Lloyd's Register Quality

Assurance (LRQA) in 2014.

• Internal policies were approved during development of

IMS; these policies define engagements of the company

members on all levels.

GMP Audits

• Audits of regulatory authorities (SÚKL, ÚSKVBL, FDA)

• Internal audits – revision of GMP and IMS compliance in

individual departments based on annual plan

• GMP Audits performed by customers

• CP audits of key suppliers to verify fulfillment of GMP

rules

History of GMP Audits – Regulatory Authorities

*State Institute for Drug Control, Czech Republic

**Institute for the State Control of Veterinary Biologicals and Medicaments, Czech Republic

Name Date Product Result

FDA Jun 2-4, 2003 (+/-)-Cloprostenol Na In compliance

SÚKL* Feb 10-11, 2004 PGE1 and PGE2 In compliance

ÚSKVBL** Jan 13, 2005 4 Veterinary API In compliance

SÚKL Feb 7-8, 2007 PGE1, PGE2, PGI2 Na In compliance

ÚSKVBL Feb 7-8, 2007 4 Veterinary API In compliance

SÚKL Jul 15, 2008 Travoprost In compliance

SÚKL May 14, 2009 Alprostadil-Alfadex In compliance

SÚKL Oct 6-7, 2009 PGE1, PGE2, PGI2 Na,

Travoprost, Latanoprost

In compliance

ÚSKVBL Mar 16-17, 2010 4 Veterinary API In compliance

FDA Mar 14-17, 2011 Travoprost, GMP In compliance

SÚKL Oct 14-15, 2012 Entecavir, GMP In compliance

ÚSKVBL Mar 12-13, 2013 4 Veterinary API In compliance

FDA March 24-27,2014 Epoprostenol, GMP In compliance

SUKL Dec 2-3, 2014 Bimatoprost, GMP In compliance

Research and Development

• Expansion of product portfolio and enhancement of

competitive ability of current production (production

scale-up, identification of critical synthesis parameters,

etc.)

• Original Corey synthesis has been modified by CP’s

unique procedures; CP claimed approx. 80 original

patents

• Cooperation with drug product manufacturers regarding

marketing applications (impurity standards preparation,

impurity profile determination)

• Creating development program of the company

Support of R&D Activities - State and EU Funds

Grant Potential

• EU fund supports the development of the Research Center –

reconstruction of the building, purchase and installation of

equipment, including safety glove boxes, which are necessary for

handling of certain active substances (incl. Epoprostenol).

Grant TIP

• Cayman Pharma has been granted a state subsidy to support

development of prostaglandins for ophthalmological purposes

(antiglaucoma APIs - Latanoprost, Bimatoprost, Travoprost).

Grant TAČR

• The Czech Technological Agency supports the development of new

veterinary derivatives.

Thank you for Your Attention