How In­smed is Pi­o­neer­ing the Next Fron­tier in Rare Dis­ease R&D

In­smed’s R&D strat­e­gy is firm­ly root­ed in putting pa­tients at the fore­front while har­ness­ing cut­ting-edge tech­nolo­gies—strate­gi­cal­ly ac­quired and de­vel­oped over the last two years—that set us on the path to be­come one of the next great biotech­nol­o­gy com­pa­nies. What lies with­in this new fron­tier? Ar­ti­fi­cial in­tel­li­gence (AI)-dri­ven pro­tein en­gi­neer­ing to re­duce the in­nate im­muno­genic­i­ty of ther­a­peu­tic pro­teins; next-gen­er­a­tion gene ther­a­pies with tar­get­ed de­liv­ery to po­ten­tial­ly ad­dress cur­rent­ly in­tractable dis­eases like Duchenne mus­cu­lar dy­s­tro­phy (DMD); RNA end-join­ing tech­nol­o­gy to en­able de­liv­ery of genes that are too large for cur­rent ve­hi­cles, which may help tar­get con­di­tions like Star­gardt dis­ease; and pro­pri­etary, al­gae-based pro­tein man­u­fac­tur­ing to in­crease pro­duc­tion speed while re­duc­ing cost.

All of these tech­nolo­gies and ca­pa­bil­i­ties build up­on the suc­cess of our first ap­proved prod­uct, a first-in-dis­ease ther­a­py for a rare pul­monary dis­ease that we de­vel­oped en­tire­ly in-house and have since com­mer­cial­ized in three glob­al re­gions. With an un­wa­ver­ing fo­cus on pur­su­ing on­ly those pro­grams that stand to make a pro­found im­pact on pa­tients’ lives, we have cul­ti­vat­ed a ro­bust pipeline ca­pa­ble of pro­duc­ing the next gen­er­a­tion of high­ly in­no­v­a­tive med­i­cines, with nu­mer­ous clin­i­cal mile­stones set to read out in the next 12 months.

Clos­ing Crit­i­cal Re­search Gaps to Open New Pos­si­bil­i­ties

In the past sev­er­al years, gene ther­a­py has be­gun to rewrite treat­ment out­comes in ar­eas like rare blood dis­or­ders, neu­ro­mus­cu­lar dis­or­ders, and vi­sion loss.1 By fo­cus­ing on the root cause of dis­ease, gene ther­a­py can aid in slow­ing or pre­vent­ing dis­ease pro­gres­sion and of­fers pa­tients a bet­ter chance at long-term im­prove­ments. Ad­vances in the un­der­stand­ing of gene ther­a­py and a grow­ing tal­ent pool with this unique ex­per­tise have ush­ered in new hope for an in­dus­try sea change.

While the tech­nol­o­gy holds in­cred­i­ble promise, a num­ber of chal­lenges per­sist: high dose re­quire­ments, of­ten lead­ing to an in­creased risk of tox­i­c­i­ty; in­abil­i­ty to tar­get large genes with cur­rent meth­ods; im­muno­genic­i­ty that makes it chal­leng­ing to re-dose pa­tients; man­u­fac­tur­ing cost and com­plex­i­ty; and unique tech­ni­cal ca­pa­bil­i­ty and ex­pe­ri­ence need­ed in gene ther­a­py man­u­fac­tur­ing.

Sim­i­lar chal­lenges ex­ist with ther­a­peu­tic pro­teins, where im­muno­genic­i­ty con­cerns con­tin­ue to lim­it the use­ful­ness of cur­rent ther­a­pies and hin­der the de­vel­op­ment of new ones. By po­ten­tial­ly ad­dress­ing these chal­lenges, In­smed is poised to make a dif­fer­ence for the many pa­tients still wait­ing on progress.

A Re­search En­gine for the Fu­ture

We are build­ing our ear­ly-stage re­search pro­gram with ex­cep­tion­al tal­ent and dis­rup­tive ca­pa­bil­i­ties to po­ten­tial­ly bring new treat­ments to mar­ket faster and at less cost than was pre­vi­ous­ly pos­si­ble. The tech­nolo­gies we have brought in-house are high­ly com­ple­men­tary and syn­er­gis­tic, both with one an­oth­er and with In­smed’s ex­ist­ing busi­ness. While less than 20 per­cent of our ex­pen­di­tures are de­vot­ed to our ear­ly-stage pro­grams, we an­tic­i­pate pro­duc­ing at least six in­ves­ti­ga­tion­al new drug ap­pli­ca­tions (INDs) by the end of 2025, en­abling us to de­vel­op po­ten­tial cut­ting-edge ther­a­pies across a broad range of rare dis­eases.

In gene ther­a­py, we’ve po­si­tioned our­selves to be unique­ly ca­pa­ble of ad­dress­ing chal­lenges in the cur­rent land­scape with nov­el, pro­pri­etary tech­nolo­gies. Our ex­pert team is pi­o­neer­ing tar­get­ed de­liv­ery meth­ods that may of­fer sig­nif­i­cant dose re­duc­tion, with the goal of an en­hanced safe­ty pro­file while re­main­ing ef­fi­ca­cious. We plan to be­gin first-in-hu­man clin­i­cal tri­als in DMD, a ge­net­ic dis­or­der char­ac­ter­ized by pro­gres­sive mus­cle de­gen­er­a­tion and weak­ness, lat­er this year, with mus­cle biop­sy da­ta ex­pect­ed in the first half of 2024. While progress has been made in the treat­ment of this dev­as­tat­ing dis­ease, we be­lieve fur­ther ex­am­i­na­tion and in­no­va­tion are need­ed.

In par­al­lel, our unique RNA end-join­ing tech­nol­o­gy en­ables the de­liv­ery of large genes that cur­rent­ly can­not be de­liv­ered us­ing tra­di­tion­al gene ther­a­py ap­proach­es. This ad­vance­ment may help us tar­get con­di­tions such as Star­gardt dis­ease, a hered­i­tary reti­nal dis­ease that caus­es vi­sion loss, typ­i­cal­ly be­gin­ning in child­hood, and that pre­vi­ous­ly could not be ad­dressed with gene ther­a­py.

Hand in hand with these ad­vances, our pro­pri­etary pro­tein deim­mu­niza­tion plat­form has the po­ten­tial to over­come the im­muno­genic­i­ty chal­lenges as­so­ci­at­ed with bio­ther­a­peu­tics by us­ing AI to reengi­neer pro­teins with­out their im­muno­genic prop­er­ties. Us­ing this plat­form, we are work­ing to de­vel­op pro­tein ther­a­peu­tics with the goal of be­ing less im­muno­genic as well as re-dos­able gene ther­a­pies to po­ten­tial­ly un­lock new, high un­met need dis­ease tar­gets. Last­ly, our pro­pri­etary al­gae-based pro­tein man­u­fac­tur­ing meth­ods have the po­ten­tial to yield re­duc­tions in both time and cost, over­com­ing many of the cur­rent chal­lenges with gene ther­a­py pro­duc­tion.

To­geth­er, these high­ly in­no­v­a­tive ap­proach­es have the po­ten­tial to make a tremen­dous im­pact on pa­tients, their fam­i­lies, and to­day’s rare dis­ease treat­ment land­scape.

Ex­pand­ing Our Im­pact

In­smed’s de­vel­op­ment pro­grams are sin­gu­lar­ly fo­cused on over­com­ing ex­ist­ing chal­lenges to de­liv­er po­ten­tial­ly life-trans­form­ing ther­a­pies—re­gard­less of modal­i­ty—to pa­tients with ur­gent un­met needs. To get there, we will be un­re­lent­ing in build­ing the next great sus­tain­able biotech­nol­o­gy com­pa­ny, hav­ing al­ready proven our suc­cess at each stage of de­vel­op­ment from re­search through com­mer­cial­iza­tion.

Our first pro­gram was built around the pur­suit of a much-need­ed treat­ment ap­proach with the high­est im­pact po­ten­tial for pa­tients – a core tenet that con­tin­ues to de­fine our or­ga­ni­za­tion­al cul­ture to­day. As we ex­pand our re­search team, tal­ent, and ca­pa­bil­i­ties with an eye to­wards the fu­ture, we will con­tin­ue to as­sess promis­ing ar­eas of po­ten­tial in­vest­ment where In­smed is unique­ly equipped to make a dif­fer­ence. To learn more about In­smed’s new fron­tier in rare dis­ease re­search, vis­it https://in­


  1. Gene Ther­a­py For Rare Dis­eases, “Gene Ther­a­py” (2023), Avail­able at: https://raredis­­a­py/.