Fol­licum, a Swedish biotech com­pa­ny born to find a treat­ment for hair loss, now has di­a­betes in its crosshairs

Fol­licum, a pep­tide-fo­cused vir­tu­al biotech com­pa­ny, was found­ed in 2011 out of a small re­search group at Lund Uni­ver­si­ty in Swe­den. The com­pa­ny has two ac­tive drug projects: the lead can­di­date, FOL-005, de­vel­oped to treat hair loss (alope­cia), and the di­a­betes can­di­date, FOL-014.

The seem­ing­ly dis­joint­ed project com­bi­na­tion can be ex­plained by the bi­o­log­i­cal con­nec­tion be­tween the two syn­dromes. Vas­cu­lar im­pair­ment caused by hy­per­glycemia of­ten leads to hair loss, which, there­fore, be­comes a sign of pos­si­ble ear­ly-stage type 2 di­a­betes ac­cord­ing to a re­cent pub­li­ca­tion.

As the com­pa­ny push­es its flag­ship hair loss treat­ment through Phase II clin­i­cal tri­als, FOL-014 is quick­ly mov­ing through the pre­clin­i­cal hur­dles and is ex­pect­ed to reach Phase I clin­i­cal tri­als in the be­gin­ning of 2020.

Alope­cia af­fects mil­lions of peo­ple world­wide and of­ten caus­es both phys­i­cal and men­tal suf­fer­ing for both men and women. While hair loss is in fo­cus when it comes to treat­ing alope­cia pa­tients, the psy­cho­log­i­cal ef­fects that come as a re­sult of the stig­ma as­so­ci­at­ed with the dis­or­der are of­ten ig­nored. But these of­ten pose a sig­nif­i­cant threat to the pa­tients as stud­ies have shown that in­di­vid­u­als with alope­cia run a high­er risk of sui­cide. This am­pli­fies the need for new treat­ments.

The most com­mon treat­ments avail­able to­day are mi­nox­i­dil (Ro­gaine) and fi­nas­teride (Prope­cia). Mi­nox­i­dil is an over-the-counter prod­uct for both men and women but on­ly 1/3 of pa­tients re­spond well to the treat­ment. Fi­nas­teride is a pre­scrip­tion med­ica­tion for men on­ly and 80% of pa­tients re­spond to it, mak­ing it more ef­fec­tive but al­so as­so­ci­at­ed with graver side ef­fects, in­clud­ing low li­bido and erec­tile dys­func­tion.

Fol­licum’s FOL-005, which is a syn­thet­ic pep­tide based on the hu­man pro­tein os­teo­pon­tin, has thus far shown promis­ing re­sults in clin­i­cal tri­als. The can­di­date is de­vel­oped to treat all in­di­vid­u­als with alope­cia and, as no side ef­fects have been re­port­ed through Phase II test­ing, it is con­sid­ered a po­ten­tial “first-in-class” treat­ment, giv­ing cre­dence to the fact that it could be­come a strong com­peti­tor to mi­nox­i­dil and fi­nas­teride.

The cross-sec­tion of the hair fol­li­cle shows treat­ment with FOL-005. Fol­licum’s sub­stance is marked by red and clear­ly shows the bind­ing to the cells. The green colour rep­re­sents the mem­branes bind­ing the dif­fer­ent cell lay­ers to­geth­er. Blue is the cell core. In the cen­tre the sin­gle hair is vis­i­ble. The bind­ing of FOL-005 clear­ly shows the im­pact on the fol­li­cle. De­liv­ery tar­get­ed and di­rect­ed to the hair fol­li­cle.

A Phase IIa study was per­formed last year at the Charite Hos­pi­tal in Berlin and the der­ma­tol­ogy CRO bioskin in Ham­burg test­ed the ef­fects of FOL-005 on the scalp of alope­cia pa­tients by in­tra­der­mal in­jec­tions. This year the com­pa­ny will run an­oth­er phase IIa tri­al op­ti­miz­ing the dose, dos­ing fre­quen­cy, and treat­ment time us­ing a new­ly de­vel­oped top­i­cal for­mu­la­tion. The study is sched­uled to be­gin late 2019.

In the mean­time, the com­pa­ny will fo­cus on find­ing a suit­able de­vel­op­ment part­ner for FOL-005 that can take on Phase IIb and Phase III stud­ies.

The suc­cess sto­ry that has been FOL-005 has led to Fol­licum’s sec­ond project, FOL-014, which is geared to­ward find­ing a treat­ment for di­a­betes and some of its com­pli­ca­tions. The re­la­tion­ship be­tween hair loss and di­a­betes is well doc­u­ment­ed, and Fol­licum has ob­served that their class of pep­tides is able to in­crease in­sulin pro­duc­tion as well as pro­tect pan­cre­at­ic β-cells, which are typ­i­cal­ly de­stroyed by the im­mune sys­tem in type 1 di­a­bet­ic pa­tients. By pre­serv­ing the func­tion of the cells, in­sulin re­lease can be main­tained, and thus im­prove the body’s ca­pac­i­ty to de­lay the on­set of type 1 di­a­betes.

Fol­licum’s pep­tide shows a good ef­fect com­pared to GLP-1, a sub­stance cur­rent­ly used in di­a­betes treat­ment.

The com­pa­ny al­so tar­get type 2 di­a­betes where FOL-014, a spin-off of their FOL-005, has pro­duced promis­ing da­ta so far. In vi­vo stud­ies have shown that FOL-014 is able to in­crease in­sulin pro­duc­tion at the same, or even high­er, rate than a com­mon GLP-1 re­cep­tor ag­o­nist, which are cur­rent­ly among the most com­mon treat­ments for di­a­betes pa­tients.

Di­a­betes af­fects close to 500 mil­lion peo­ple world­wide, and glob­al preva­lence among adults has al­most dou­bled since 1980, from 4.3%t to 9% in 2014. These num­bers are not ex­pect­ed to come down any time soon, which means the eco­nom­ic bur­den on so­ci­ety will on­ly get worse.

Ac­cord­ing to the Amer­i­can Di­a­betes As­so­ci­a­tion, glob­al health­care costs re­lat­ed to di­a­betes are es­ti­mat­ed to dou­ble by 2030, reach­ing close to $2.5 tril­lion. Much of the cost is due to se­ri­ous com­pli­ca­tions such as heart at­tack, stroke, nerve dam­age or kid­ney dis­ease caused by the un­der­ly­ing in­abil­i­ty of the di­a­bet­ic pa­tient to ab­sorb sug­ar (glu­cose) from the blood and use it as en­er­gy to the sur­round­ing cells of the body.

And that’s where Fol­licum hopes to make an im­pact in a chal­lenge to its com­peti­tors. The da­ta re­trieved thus far from FOL-014 sug­gests that the com­pound could be ef­fec­tive in great­ly re­duc­ing such com­pli­ca­tions, some­thing that drugs cur­rent­ly on the mar­ket are not able to do ef­fec­tive­ly. This could, there­fore, have a sub­stan­tial im­pact on the di­a­betes mar­ket.

Fol­licum has laid out a sol­id foun­da­tion for its di­a­betes project and has tak­en key steps to make sure the project con­tin­ues to grow on sta­ble foot­ing. The project it­self is run in col­lab­o­ra­tion with one of the world-lead­ing di­a­betes re­search groups, Jan Nils­son’s group based at Lund Uni­ver­si­ty’s Di­a­betes Cen­tre in Malmö.

Through that col­lab­o­ra­tion, Fol­licum has placed it­self in good com­pa­ny with ma­jor phar­ma play­ers such as No­vo Nordisk, Pfiz­er, and John­son & John­son In­no­va­tion by join­ing the in­ter­na­tion­al di­a­betes con­sor­tium, LUDC-IRC, al­so based in Malmö. More­over, in No­vem­ber 2018, the com­pa­ny pro­ceed­ed to broad­en its patent port­fo­lio by sub­mit­ting a new patent ap­pli­ca­tion to pro­tect new as­pects of its di­a­betes pep­tide class.

The fact that the com­pa­ny is part of LUDC-IRC gives Fol­licum — in ad­di­tion to a def­i­nite seal of qual­i­ty — ac­cess to a large net­work and val­i­dat­ed di­a­betes mod­els. Through its in­ter­na­tion­al net­work, Fol­licum has been giv­en the op­por­tu­ni­ty to dis­cuss how to tai­lor its re­search in the most op­ti­mal man­ner. This has re­sult­ed in a de­ci­sion to dif­fer­en­ti­ate it­self from its com­peti­tors by fo­cus­ing on the re­duc­tion of di­a­betes com­pli­ca­tions.

The com­pa­ny aims to out-li­cense the can­di­date dur­ing pre­clin­i­cal phase/Phase I at the lat­est.

One of the biggest chal­lenges Fol­licum faces is be­ing able to se­cure fi­nanc­ing to ad­vance its projects ac­cord­ing to plan. Just re­cent­ly, the com­pa­ny raised 15 MSEK through war­rants as­so­ci­at­ed with a rights is­sue from 2018. Ac­cord­ing to the vir­tu­al­ly-led Fol­licum, who con­tracts var­i­ous spe­cial­ists on a need-by-need ba­sis, the mon­ey raised will al­low the com­pa­ny to main­tain suf­fi­cient pace in both projects and to ad­vance busi­ness de­vel­op­ment ac­tiv­i­ties.

Fur­ther cap­i­tal will like­ly be nec­es­sary, nonethe­less, to ac­com­mo­date the com­mence­ment of the phase IIa study in­volv­ing a top­i­cal for­mu­la­tion for FOL-005.

Re­gard­less of the struc­ture of the busi­ness mod­el, the biggest risk with­in phar­ma­ceu­ti­cal de­vel­op­ment is the in­her­ent in­se­cu­ri­ty of the projects: there is sim­ply no way to pre­dict with cer­tain­ty if a study will achieve pos­i­tive re­sults. Thus, by tak­ing its main can­di­date FOL-005 through an­oth­er clin­i­cal study, Fol­licum is tak­ing a risk. How­ev­er, as there is pos­i­tive Phase II da­ta on the in­ject­ed ver­sion of the can­di­date, the fol­low-up study with the top­i­cal for­mu­la­tion presents sig­nif­i­cant­ly low­er risks than an av­er­age Phase II study. In ad­di­tion, the top­i­cal can­di­date re­cent­ly showed promis­ing re­sults in an in vi­vo-mod­el. Hence, the up­com­ing clin­i­cal study is like­ly to pay off in the long run if the com­pa­ny is able to catch the at­ten­tion of po­ten­tial out-li­cens­ing part­ner, as Fol­licum cur­rent­ly lacks clin­i­cal da­ta on the fi­nal prod­uct.

Over­all, Fol­licum seems to be in good po­si­tion to out-li­cense FOL-005, as com­pe­ti­tion with­in hair growth is lim­it­ed, mak­ing the com­pa­ny’s in­no­v­a­tive ap­proach a good base for a fu­ture part­ner­ship.

Fol­licum has been trad­ing its shares on the Spot­light Stock Mar­ket (tick­er: FOL­LI) since the end of 2014. Dur­ing that pe­ri­od Fol­licum has been able to reach all mile­stones with­in the com­mu­ni­cat­ed bud­get and time, which shows that the com­pa­ny has the ca­pac­i­ty to man­age its pep­tide-based projects ef­fi­cient­ly and sig­nals that the com­pa­ny is in a strong po­si­tion to move for­ward.

A full sta­tus re­port on Fol­licum by Bio­S­tock can be viewed here.

Im­age cred­it: Shut­ter­stock