Topics. Brief company presentation. FluidCrystal Injection Depot. FluidCrystal Nanoparticles

Transcription

1 Nanostructured lipid-based liquid crystaline systems for controlled release of drug substances September 2010 Catalin Nistor Research Director, Camurus AB, Lund, Sweden 1

2 Topics Brief company presentation Technology FluidCrystal Injection Depot FluidCrystal Nanoparticles 2

3 Camurus - Snapshot profile Headquarter in Lund, Sweden Medicon Valley Member of GS Development group Strong committed investor Broad late/mid stage drug product pipeline Global technology leader in lipid-based drug delivery Strategic corporate partnerships 3 COMPANY

4 Camurus - Advancing pipeline 4 COMPANY

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6 Controlling lipid self-assembly GDO L 2 Reversed micellar cubic, space group Fd3m I 2 Reversed hexagonal H 2 Water L PC 6 TECHNOLOGY

7 Controlling lipid self-assembly Nanoparticle formation FluidCrystal NP GDO L 2 +fragmenting agent, dilution/sheari I 2 H 2 Water L PC Cubosome, Flexosome, Hexosome 7 TECHNOLOGY

8 Camurus Drug Delivery Platforms 8 TECHNOLOGY

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10 The best dose is the one you don t give Reduced frequency of administration is vital in an increasingly competitive marketplace Patient convenience Increased adherence / compliance Enhanced safety profile Dose sparing Life-cycle management strategies Enable development & new indication 10 FluidCrystal Injection depot

11 Controlled- o vs. Immediate-release e ease 100 IR CR Dru ug Concent tration, ng /ml The erapeutic wi indow Time, h 11 FluidCrystal Injection depot

12 Essential requirements Compatibility with administration device/route Demonstrated safety and tolerability Demonstrated in vivo functionality Product storage stability Manufacturability at commercial scales 12 FluidCrystal Injection depot

13 Illustration of depot product principle 13 FluidCrystal Injection depot

14 LC phase structure vs time GDO L 2 I 2 H 2 Water L PC 14 FluidCrystal Injection depot

15 In vitro release vs composition % fluoresce ein release % fluorescein rele ease wt% GMO with respect to SPC wt% GDO with respect to SPC 15 FluidCrystal Injection depot

16 Leuprolide FluidCrystal Leuprolide: gonadorelin (LHRH) analogue, linear nonapeptide The active ingredient in Procren and Eligard, approved for treatment of prostate cancer 16 FluidCrystal Injection depot

17 Leuprolide FluidCrystal : one month target duration FC leuprolide versus marketed products leuprolid de concen ntration (n ng/ml) Plasma 1000 FC leuprolide 7.5 mg Eligard 7.5 mg FC leuprolide 3.75 mg 100 Procren Depot 3.75 mg Time (days) Rats n = 6 17 FluidCrystal Injection depot

18 Leuprolide FluidCrystal : one month target duration - s.c. versus i.m. concentr ration (ng g/ml) Plasma le euprolide 100 intramuscular subcutaneous Time (days) Dogs n = 6 (SC) n=4(im) 18 FluidCrystal Injection depot

19 Leuprolide FluidCrystal : l Demonstrated long-term release in men Serum leuprolid de concen ntration (ng/ml) , ml (7.5 mg) abdominal s.c ml (7.5 mg) deep s.c , Time (days) Phase IIa data n/group = 6 n= 27 mean + sd 19 FluidCrystal Injection depot

20 Leuprolide FluidCrystal: l Demonstrated testosterone suppression Median testostero one conc centration n (ng/dl) ml l(75 (7.5 mg) abdominal s.c ml (7.5 mg) deep s.c Time (days) Phase IIa data n/group = 6 n=27 20 FluidCrystal Injection depot

21 Octreotide FluidCrystal Octreotide: somatostatin analogue, cyclic octapeptide The active ingredient in Sandostatin and Sandostatin LAR (Novartis), approved for treatment of acromegaly and carcinoid syndrome 21 FluidCrystal Injection depot

22 Octreotide FluidCrystal versus Sandostatin LAR tration (n ng/ml) ml (2.45 mg) SC 0.3 ml (7.35 mg) SC 1 ml (24.5 mg) SC 0.3 ml (7.35 mg) IM Sandostatin LAR (20mg) Astruc et al., 2005 Phase I n = 6 ctreotide e concent 1 0,1 Serum o 0, Time (days) 22 FluidCrystal Injection depot

23 Octreotide FluidCrystal : Tuning of release duration 24 hours vs. 1 week Plasma octreotid de concen ntration ( ng/ml) Saline solution SC FluidCrystal l SC one day FluidCrystal SC one week Time (hours) Rats n = 6 (SC) 23 FluidCrystal Injection depot

24 Somatostatin FluidCrystal Somatostatin: peptide hormone (14 amino acids, cyclic) with ubiquitous distribution, regulating the endocrine system and neurotransmission Possible applications in acromegaly, Cushing s syndrome, different types of cancer, etc. 24 FluidCrystal Injection depot

25 Somatostatin t ti (1-14) 14) FluidCrystal : l one week target duration Rats N = 24 (SC) Plasma a SST con ncentration n (ng/ml) mg/kg 30 mg/kg 40 mg/kg Endogenous SST Time (days) AUC (ng/ml L/days) Dose (mg/kg) 25 FluidCrystal Injection depot

26 Buprenorphine FluidCrystal Buprenorphine: partial µ-opioid receptor agonist with a wider safety window than other opioids Existing products: sublingual tablets Subutex and Subuxone, and in the s.c implant Probuphine. Aproved for treatment of drug abuse and management of pain 26 FluidCrystal Injection depot

27 Buprenorphine FluidCrystal : l one month target duration Plasma co oncentrat tion (ng/m ml) mg/kg g 50 mg/kg 75 mg/kg Time (days) Rats n = 10 (SC) 27 FluidCrystal Injection depot

28 Buprenorphine FluidCrystal : l one week target duration Plasma co oncentra ation (ng/m ml) Rats n = 6 (SC)( ) 5 mg/kg 10 mg/kg 20 mg/kg 50 mg/kg Time (days) AUC inf. (n ng/ml*d) Dose (mg/kg) 28 FluidCrystal Injection depot

29 Peptide storage stability octreotide and leuprolide in prefilled syringes % of start drug conc centration n 120 OCT 25 C/60%RH OCT 40 C/75%RH LEU 25 C/60%RH LEU 40 C/75%RH Time (months) 29 FluidCrystal Injection depot

30 Small molecule storage stability buprenorphine, benzydamine and diclofenac 120 drug con ncentratio on % of start BUP 25 C/60%RH BZD 25 C/60%RH DCF 25 C/60%RH Time (months) 30 FluidCrystal Injection depot

31 Easy manufacturing by standard processes 31 FluidCrystal Injection depot

32 FluidCrystal Injection depot: Competitive landscape example Leuprolide products Procren Depot 3.75 mg 1 ml/25g/reconstitution/s.c. Octreotide products Sandostatin LAR 10, 20, 30 mg 2.5 ml/19g/reconstitution/i.m. /i Prosenze 7.5 mg 0.25 ml/27g/ready-to-use/s.c. CAM , 20, 30 mg ml/25g/ready-to-use/s.c. Eligard 7.5 mg 0.25 ml/20g/reconstitution/s.c. Somatuline Autogel 60, 90, 120 mg ml/16g/ready-to-use/deep s.c. 32 FluidCrystal Injection depot

33 FluidCrystal Injection depot Key competitive features: Strong intellectual t l property True ready-to-use product design Easy manufacturing by standard processes High drug payloads, easily dose adjustable Subcutaneous and intramuscular administration Small needle size (23-27 gauge) Low dose dumping, consistent release Tuneable duration from one day to several months Good stability of loaded drug in the lipid matrix Demonstrated safety in clinical trials 33 FluidCrystal Injection depot

34 Self-assembled ed lipid superstructures: st uctu es Beyond emulsions and liposomes Barauskas J, Johnsson M, Tiberg F NANO LETTERS, 5 (8), , FluidCrystal NP

35 Extended somatostatin circulation time by association with reverse micellar cubic phase nanoparticles SPC/GDO/P80 (40/40/20 w/w) Cervin C, Vandoolaeghe P, et. al. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCE 36 (4-5), , FluidCrystal NP

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