Epione Therapeutics

Biomaterial-based local sustained delivery allows long term effective local drug levels resulting in lasting pain relief.

Effective, safe and long-term pain relief in osteoarthritis and chronic low back pain can be achieved by local biomaterial-based controlled release of drugs; drug-loaded biomaterials slowly release their cargo by diffusion and biomaterial degradation. A solid body of preclinical evidence was generated on intra-articular and intradiscal release of the anti-inflammatory drug celecoxib. Celecoxib is an efficient anti-inflammatory drug that has serious side effects upon oral intake, and has difficulties reaching the joint fluid and intervertebral disc at therapeutic levels via the blood. However, celecoxib delivered intra-articularly and intradiscally by biomaterial microspheres was observed to be safe and induce long-term reduction of inflammation and pain in small animals and canine patients, at doses of less than the equivalent of one single pill for daily intake. Epione Therapeutics proprietory biomaterial platform is already in human patients for other drug delivery applications. Moreover, the platform also allows for loading and delivery of other payloads including protein drugs, thereby also paving the way towards, for example, the delivery of regenerative factors.

BACKGROUND LITERATURE

 

 

Tellegen A, Beukers M, Jansen I, van Klaveren N, How KL, Woike N, Mihov G, Thies J, Teske E, Creemers L, Tryfonidou M, Meij B. Intra-articular slow-release triamcinolone acetonide from polyesteramide microspheres as a treatment for osteoarthritis. Pharmaceutics. 2021 Mar 11;13(3):372 https://doi.org/10.3390/pharmaceutics13030372 

 

Rudnik-Jansen I, Schrijver K, Woike N, Tellegen A, Versteeg S, Emans P, Mihov G, Thies J, Eijkelkamp N, Tryfonidou M, Creemers L. Intra-articular injection of triamcinolone acetonide releasing biomaterial microspheres inhibits pain and inflammation in an acute arthritis model. Drug Deliv. 2019 Dec;26(1):226-236. https://doi.org/10.1080/10717544.2019.1568625 

 

Rudnik-Jansen I, Tellegen AR, Pouran B, Schrijver K, Meij BP, Emans PJ, de Gendt E, Thomas RE, Kik MJL, de Visser HM, Weinans H, Egas A, van Maarseveen E, Woike N, Mihov G, Thies J, Tryfonidou MA, Creemers LB. Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing. Br J Pharmacol. 2019 Oct;176(20):4050-4064. https://doi.org/10.1111/bph.14817  

 

Rudnik-Jansen I, Tellegen A, Beukers M, Öner F, Woike N, Mihov G, Thies J, Meij B, Tryfonidou M, Creemers L. Safety of intradiscal delivery of triamcinolone acetonide by a poly(esteramide) microsphere platform in a large animal model of intervertebral disc degeneration. Spine J. 2019 May;19(5):905-919.

 

Rudnik-Jansen I, Woike N, de Jong S, Versteeg S, Kik M, Emans P, Mihov G, Thies J, Eijkelkamp N, Tryfonidou M, Creemers L. Applicability of a Modified Rat Model of Acute Arthritis for Long-Term Testing of Drug Delivery Systems. Pharmaceutics. 2019 Feb 7;11(2). https://doi.org/10.3390/pharmaceutics11020070 

 

Tellegen AR, Rudnik-Jansen I, Pouran B, de Visser HM, Weinans HH, Thomas RE, Kik MJL, Grinwis GCM, Thies JC, Woike N, Mihov G, Emans PJ, Meij BP, Creemers LB, Tryfonidou MA. Controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritis. Drug Deliv. 2018 Nov;25(1):1438-1447 https://doi.org/10.1080/10717544.2018.1482971 

 

Tellegen AR, Rudnik-Jansen I, Beukers M, Miranda-Bedate A, Bach FC, de Jong W, Woike N, Mihov G, Thies JC, Meij BP, Creemers LB, Tryfonidou MA. Intradiscal delivery of celecoxib-loaded microspheres restores intervertebral disc integrity in a preclinical canine model. J Control Release. 2018 Sep 28;286:439-450. https://doi.org/10.1016/j.jconrel.2018.08.019 

 

Tellegen AR, Willems N, Beukers M, Grinwis GCM, Plomp SGM, Bos C, van Dijk M, de Leeuw M, Creemers LB, Tryfonidou MA, Meij BP. Intradiscal application of a PCLA-PEG-PCLA hydrogel loaded with celecoxib for the treatment of back pain in canines: What’s in it for humans? J Tissue Eng Regen Med. 2018 Mar;12(3):642-652).

 

Rudnik-Jansen I, Colen S, Berard J, Plomp S, Que I, van Rijen M, Woike N, Egas A, van Osch G, van Maarseveen E, Messier K, Chan A, Thies J, Creemers L. Prolonged inhibition of inflammation in osteoarthritis by triamcinolone acetonide released from a polyester amide microsphere platform. J Control Release. 2017 Mar 9;253:64-72. https://doi.org/10.1016/j.jconrel.2017.03.014 

 

Willems N, Mihov G, Grinwis GC, van Dijk M, Schumann D, Bos C, Strijkers GJ, Dhert WJ, Meij BP, Creemers LB, Tryfonidou MA. Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration. J Biomed Mater Res B Appl Biomater. 2017 May;105(4):707-714. https://doi.org/10.1002/jbm.b.33579 

 

Janssen M, Timur UT, Woike N, Welting TJ, Draaisma G, Gijbels M, van Rhijn LW, Mihov G, Thies J, Emans PJ. Celecoxib-loaded PEA microspheres as an auto regulatory drug-delivery system after intra-articular injection. 2016 J. Control. Release 244, 30–40. https://doi.org/10.1016/j.jconrel.2016.11.003 

 

Willems N, Yang HY, Langelaan ML, Tellegen AR, Grinwis GC, Kranenburg HJ, Riemers FM, Plomp SG, Craenmehr EG, Dhert WJ, Papen-Botterhuis NE, Meij BP, Creemers LB, Tryfonidou MA. Biocompatibility and intradiscal application of a thermoreversible celecoxib-loaded poly-N-isopropylacrylamide MgFe-layered double hydroxide hydrogel in a canine model. 2015 Arthr Res Ther Aug 20;17(1):214. https://doi.org/10.1186/s13075-015-0727-x 

 

 Yang HY, van Dijk M, Licht R, Beekhuizen M, van Rijen M, Janstål MK, Öner FC, Dhert WJ, Schumann D, Creemers LB. Applicability of a newly developed bioassay for determining bioactivity of anti-inflammatory compounds in release studies–celecoxib and triamcinolone acetonide released from novel PLGA-based microspheres. Pharm Res. 2015 Feb;32(2):680-90.