A quiver of ar­rows for im­mune dis­or­ders: Pan­dion scores $80M in fresh fund­ing

Sci­en­tists be­gan with mak­ing re­com­bi­nant ver­sions of nat­u­ral­ly-oc­cur­ring hu­man pro­teins, then grad­u­at­ed to mon­o­clon­al an­ti­bod­ies. Now, rather than repli­cat­ing moi­eties with­in the body, re­searchers are mod­i­fy­ing these mol­e­cules to have pre­cise bi­ol­o­gy in a func­tion­al man­ner.

This tech­nol­o­gy, re­ferred to as bis­pe­cif­ic an­ti­bod­ies, is al­ready be­ing em­ployed to fight can­cer. In ear­ly 2018, Pan­dion Ther­a­peu­tics was born to re­verse-en­gi­neer the sci­ence in­to the realm of au­toim­mune and in­flam­ma­to­ry dis­or­ders.

Rahul Kakkar

Mon­o­clon­al an­ti­bod­ies are de­signed to in­hib­it a path­way, but Pan­dion is tak­ing a mol­e­cule that the body cre­ates, and en­gi­neer­ing it for the bi­ol­o­gy that we want, said com­pa­ny chief Rahul Kakkar in an in­ter­view.

As the com­pa­ny shep­herds its lead ther­a­py in­to pa­tients, on Wednes­day it raised a meaty $80 mil­lion in a fresh round of fi­nanc­ing.

Pan­dion, which counts Astel­las as a part­ner, has cre­at­ed com­po­nents that can be mixed and matched to cre­ate mol­e­cules that have both the bi­o­log­ic and the chem­i­cal ther­a­peu­tic prop­er­ties that we want, Kakkar ex­plained.

“The way I like to think about it is our mol­e­cules rep­re­sent ar­rows, with­in a quiver of ar­rows that rep­re­sents our pipeline,” he said. “So each of these ar­rows has an ar­row­head. The ar­row­head is an en­gi­neered vari­ant of some­thing our bod­ies nat­u­ral­ly use to con­trol the im­mune sys­tem.”

The ar­row­head in the com­pa­ny’s lead pro­gram — PT101 — is a mu­tat­ed vari­ant of in­ter­leukin two. Nat­u­ral­ly, the body us­es IL-2 to ex­pand reg­u­la­to­ry T cells and to en­hance con­ven­tion­al pro-in­flam­ma­to­ry T cells. Pan­dion’s IL-2 two has been en­gi­neered to be high­ly spe­cif­ic for reg­u­la­to­ry T cells, but to have no ef­fect on the oth­er cells. The ther­a­py is cur­rent­ly be­ing eval­u­at­ed in healthy vol­un­teers — and if all goes well, come 2021, the com­pound will be test­ed in ul­cer­a­tive col­i­tis pa­tients.

The ar­row­head is in charge of the bi­ol­o­gy, but the tail gives the ar­row­head phar­ma­cother­a­peu­tic prop­er­ties that we want. “So we can mar­ry an FC fu­sion, for in­stance, which gives half-life ex­ten­sion, so then that ar­row­head re­sides with­in the sys­temic cir­cu­la­tion, has sys­temic im­mune-mod­u­la­to­ry prop­er­ties and be­haves like an in­jectable bi­o­log­ic,” Kakkar said.

The next junc­ture, which Pan­dion has un­der de­vel­op­ment, is cre­at­ing a bi­func­tion­al or bis­pe­cif­ic, so the tail end ac­tu­al­ly has a func­tion, rather than just half-life ex­ten­sion.

“That tail…is de­signed as a teth­er or a dock, where it binds the ar­row­head with­in an or­gan of in­ter­est so we can, there­fore, guide the ar­row­head in­to spe­cif­ic or­gan sys­tems,” Kakkar said. “So, for in­stance, we can guide it in­to the be­ta cells of the pan­creas, which is where our col­lab­o­ra­tion with Astel­las fo­cus­es.”

The word Pan­dion is the genus name for the os­prey (or a sea hawk), a brown-and-white bird of prey. Spread­ing its wings, it swoops down to wa­ter sur­faces to seize un­sus­pect­ing fish us­ing its talons. “The im­age of a very pre­cise hit with wing­spread ba­si­cal­ly looks like an an­ti­body bind­ing to a very spe­cif­ic lo­cal­iza­tion in ge­og­ra­phy and so that’s ex­act­ly what our mol­e­cules do par­tic­u­lar­ly in the bis­pe­cif­ic for­mat,” said Kakkar.

The Se­ries B was led by Ac­cess Biotech­nol­o­gy, Box­er Cap­i­tal, RA Cap­i­tal and Or­biMed and in­clud­ed the par­tic­i­pa­tion of Po­laris Part­ners, Ver­sant Ven­tures, Roche Ven­ture Fund, SR One, JDRF T1D Fund and BioIn­no­va­tion Cap­i­tal. The Boston-based start­up raised $58 mil­lion in Jan­u­ary 2018.

De­spite the dis­rup­tions faced by the on­go­ing coro­n­avirus pan­dem­ic, since the biotech in­dus­try is con­sid­ered es­sen­tial in Boston, the com­pa­ny con­tin­ues to work on its com­pounds, al­though all non-lab per­son­nel are work­ing re­mote­ly.

“Frankly speak­ing, the need of pa­tients suf­fer­ing from au­toim­mune dis­ease con­tin­ues and so as long as that need is there, we con­tin­ue to be fo­cused on ex­e­cut­ing on our goals,” Kakkar said.

That be­ing said, work­ing from home is hard­ly a walk in the park. ” I think we’re all sup­port­ing each oth­er as best we can, but I think it’s a chal­lenge for every­one.”

Paul Hudson, Sanofi CEO (Getty Images)

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