Pro­ject status/ re­sults

Tar­get­AMD 1.0

The Tar­get­AMD 1.0 pro­ject got fund­ing from the European Uni­on from Novem­ber 1, 2012 to April 30, 2018. To con­tin­ue the­ra­py de­vel­op­ment, the private found­a­tion Pro­visu agreed to fin­an­cially sup­port the pro­ject in two phases; the pre-clini­cal phase was thought to col­lect pre-clini­cal data re­quired to get the ap­prov­al for the clini­cal study ne­ces­sary to start the phase Ib/IIa of the clini­cal study. Phase I las­ted from March 1, 2020 to April 30, 2023, while phase II will start as soon as we will get the ap­prov­al to per­form the clini­cal tri­al, which is as­sumed for fall 2023.

The ap­proach sug­gests to ge­net­ic­ally modi­fy pa­tient-de­rived iris cells (iris pig­ment ep­ithe­lial, IPE, cells) with the gene cod­ing for the factor PEDF (pig­ment ep­ithe­li­um-de­rived factor) that is in­hib­it­ing ab­nor­mal ves­sel growth in the eye. The cells will be trans­planted between the RPE cells and the reti­na of the pa­tients. RPE, reti­nal pig­ment ep­ithe­lial cells, are sup­port­ive cells loc­ated be­low the reti­na and in dir­ect con­tact with the out­er cells of the reti­na, the visu­al cells. With­in 60 min, cells will be col­lec­ted, ge­net­ic­ally mod­i­fied and trans­planted to the same pa­tient. For the ge­net­ic modi­fic­a­tion, we are us­ing safe, non-vir­al, free-of-an­ti­gi­ot­ic-res­ist­ance-gene (pFAR4) SB100X gene trans­port vec­tors.

The main ob­ject­ives of the pro­ject are the:

1) im­prove­ment of safety of the ap­proach and its eval­u­ation,

2) es­tab­lish­ment of the treat­ment,

3) de­term­in­a­tion of the be­ne­fi­cial ef­fect in ex­per­i­ment­al mod­els of ves­sel growth in the eye,

4) pro­duc­tion of re­agents com­pli­ant to re­quired hy­giene meas­ures,

5) com­pil­a­tion of ex­per­i­ment­al data in an ap­plic­a­tion dossier to the Swiss reg­u­lat­ory au­thor­ity for ap­prov­al of a phase Ib/IIa clini­cal tri­al and its com­ple­tion,

6) pub­lic­a­tion of re­sults to the scien­tific com­munity and the pub­lic, and

7) ex­ploit­a­tion of newly de­veloped products.

Most goals were already reached in the first pro­ject phase: Drug pro­duc­tion re­quires spe­cial hy­giene meas­ures (“Good Man­u­fac­tur­ing Prac­tice”, GMP) and the Tar­get­AMD con­sor­ti­um ac­com­plished the first GMP-com­pli­ant pro­duc­tion of SB100X-pFAR4 vec­tors for non-vir­al gene the­ra­py. The con­sor­ti­um in­creased the safety of the SB100X sys­tem by com­bin­ing it with the pFAR4-mini­plas­mids, GMP-cer­ti­fied pro­duced and con­trolled. Spe­cial equip­ment, the Clinipor­at­orTM and as­so­ci­ated mi­cro­cu­vettes, and re­agents have been de­veloped, the pro­duc­tion pro­ced­ure has been con­tinu­ously im­proved and re­lease cri­ter­ia and qual­ity con­trols have been defined for the cell product, i.e., 5–10*103 freshly isol­ated, ge­net­ic­ally mod­i­fied (PEDF-trans­fec­ted) IPE cells, to be used in hu­man. The ef­fect and safety of the treat­ment were con­firmed in 3 dif­fer­ent ex­per­i­ment­al mod­els. Ne­ces­sary doc­u­ments for a GMP-com­pli­ant pro­duc­tion and per­form­ance of a clini­cal tri­al are in place. The Tar­get­AMD con­sor­ti­um raised aware­ness for the pro­ject by util­ising all avail­able me­dia from a web­site ( to in­form­a­tion events for the pub­lic and 8 pub­lished peer-re­viewed pa­pers in scien­tific journ­als, 6 of which are gold Open Ac­cess, ac­cess­ible at no costs. The planned phase Ib/IIa clini­cal tri­al will be the first study world­wide test­ing the safety of the com­bined non-vir­al SB100X-pFAR4-mini­plas­mids in hu­man be­ings, for which the can­ton­al eth­ic­al com­mis­sion of Geneva already gave its ap­prov­al. Im­ple­ment­a­tion in oph­thal­mo­lo­gic clin­ics is fa­cil­it­ated since a ded­ic­ated train­ing and the Tar­get­AMD kit are suf­fi­cient for its per­form­ance, open­ing the door for the Tar­get­AMD treat­ment to be­come a routine the­ra­py.

Devices and re­agents de­veloped in Tar­get­AMD 1.0

TargetAMD Devices and reagents

To be able to eval­u­ate posi­tively our clini­cal tri­al ap­plic­a­tion, Swiss­med­ic re­ques­ted ad­di­tion­al ef­fi­ciency and tox­icity data. In the last three years we demon­strated stable ex­pres­sion of the thera­peut­ic pro­tein PEDF for 18 months in hu­man IPE cells. A risk for can­cer de­vel­op­ment has been ex­cluded as was the tox­icity of the trans­planted cells. We are now in the pro­cess of data ana­lys­is and dossier pre­par­a­tion for the re­sub­mis­sion to Swiss­med­ic.

Trans­planted cells in ef­fi­ciency and safety stud­ies

TargetAMD Visualization of transplanted cells