Can a new protein bring RNA drugs where they can’t reach?

Amber Tong

Senior Editor

Sue Dil­lon re­mem­bers the un­cer­tain­ty when she first left J&J to start her own biotech around a new kind of mol­e­cules called cen­tyrins.

Sue Dil­lon

J&J had al­ready li­censed the tech, which was de­vel­oped by her co-founder Karyn O’Neil at the phar­ma gi­ant’s Cen­tyrex unit, to two com­pa­nies for use in CAR-T and ra­dio­phar­ma­ceu­ti­cals. But Aro Bio­ther­a­peu­tics want­ed to ap­ply it to what was still a nascent area: RNA med­i­cines, en­com­pass­ing both an­ti­sense oligonu­cleotides and siR­NA ther­a­pies.

“There was a lot of skep­ti­cism out there around whether or not oligonu­cleotides would be­come a sig­nif­i­cant drug plat­form,” she told End­points News. “I don’t think any­body doubts that now.”

For all the progress, though, the need that the duo saw re­mains. Out­side the liv­er and cer­tain dis­eases primed for lo­cal de­liv­ery, drug ­mak­ers have had trou­ble de­liv­er­ing these drugs to oth­er tis­sues. Aro’s pro­posed so­lu­tion was promis­ing and per­ti­nent enough that af­ter J&J pro­vid­ed the ini­tial $13 mil­lion to get things off the ground, Io­n­is, a gi­ant in the an­ti­sense nu­cleotide field, signed up for a dis­cov­ery pact at the be­gin­ning of 2020.

One year lat­er, Dil­lon and O’Neil are ready to steer their own can­di­dates to­ward the clin­ic, armed with $88 mil­lion in Se­ries A fund­ing pro­vid­ed by the ex­ist­ing in­vestors at John­son & John­son In­no­va­tion – JJDC, Io­n­is and Bio­Mo­tiv, as well as new back­ers led by North­pond Ven­tures and Cowen Health­care (the oth­ers are Health­Cap, BVF Part­ners and Ridge­back Cap­i­tal).

If the con­cept checks out — and Aro is lean­ing on some se­ri­ous proof-of-con­cept from O’Neil’s J&J days that it would — it promis­es to change not just an­ti­sense but a slew of ge­net­ic med­i­cines that are re­shap­ing the de­f­i­n­i­tion of a drug.

Cen­tyrins, Dil­lon ex­plained, are mod­eled on a hu­man pro­tein from the fi­bronectin fam­i­ly that vague­ly re­sem­bles an anti­gen bind­ing do­main of a very large an­ti­body. They are small (just one-fif­teenth the size of an an­ti­body) but bind to cell sur­face re­cep­tors with high affin­i­ty, and they can be eas­i­ly man­u­fac­tured in E. coli in the lab.

Karyn O’Neil

Not on­ly has O’Neil fig­ured out a way to con­ju­gate them to RNA mol­e­cules, her team can al­so cre­ate bis­pe­cif­ic or mul­ti­spe­cif­ic cen­tyrins to se­lect for cer­tain cells that have all the re­cep­tors.

The com­pa­ny isn’t say­ing much about the pipeline oth­er than that the ini­tial pro­grams will tar­get mus­cle dis­eases and im­munol­o­gy — Dil­lon’s ex­pert area at J&J — and range from the rare, or­phan dis­or­der to more com­mon ail­ments. As is com­mon for an ear­ly-stage ven­ture, the CEO al­so re­frained from com­mit­ting to a time­line for en­ter­ing the clin­ic but not­ed the fund­ing should last them two to three years.

In par­al­lel with the lead pro­grams, the team of 20 is al­so ex­plor­ing ways to sys­tem­i­cal­ly de­liv­er mR­NA, DNA or CRISPR/Cas ma­chin­ery — any­thing that’s wrapped in nanopar­ti­cles — to tar­get tis­sues.

“I think that the biggest sin­gle thing over the last 3 years is the emer­gence of broad­ly ge­net­ic med­i­cines as the ma­jor class of med­i­cines for the fu­ture, and along with that, the recog­ni­tion that a ma­jor chal­lenge fac­ing the en­tire field of any of those types of med­i­cines is the chal­lenge of tis­sue spe­cif­ic de­liv­ery,” Dil­lon said. “That’s where Aro comes in. And that’s why I be­lieve even more than I did in 2018 when we first start­ed the com­pa­ny that there is just enor­mous po­ten­tial here for us to re­al­ly make a dif­fer­ence.”