Af­ter some ear­ly hic­cups in its man­u­fac­tur­ing pro­ce­dures for its gene ther­a­py drug tar­get­ing wet age-re­lat­ed mac­u­lar de­gen­er­a­tion, Cal­i­for­nia biotech Ad­verum has ad­dressed those con­cerns and is prim­ing the pump for a com­mer­cial launch.

The oc­u­lar and oth­er rare dis­ease-fo­cused gene ther­a­py com­pa­ny will in­vest $80 mil­lion in a new cGMP man­u­fac­tur­ing fa­cil­i­ty in North Car­oli­na’s bustling Re­search Tri­an­gle Park that by 2023 will be ready to man­u­fac­ture com­mer­cial sup­ply of AD­VM-022, Ad­verum’s in­trav­it­re­al ther­a­peu­tic, the com­pa­ny said Thurs­day.

The 174,000 square-foot fa­cil­i­ty will in­clude four 1,000-liter biore­ac­tors, with space for fu­ture ex­pan­sion, and will cre­ate more than 200 jobs. In ad­di­tion to its $80 mil­lion in­vest­ment, Ad­verum will gain up to $9 mil­lion in North Car­oli­na state and lo­cal in­cen­tives.

An­gela Thedin­ga

“Our new in-house com­mer­cial man­u­fac­tur­ing fa­cil­i­ty sets the foun­da­tion of our over­all man­u­fac­tur­ing strat­e­gy,” An­gela Thedin­ga, Ad­verum’s chief tech­nol­o­gy of­fi­cer, said in a state­ment. “Our new site will pro­vide ded­i­cat­ed com­mer­cial sup­ply, while we con­tin­ue to lever­age CMO part­ner­ships for flex­i­ble clin­i­cal and ad­di­tion­al com­mer­cial sup­ply.”

In 2020, Phase I tri­al da­ta from AD­VM-022 start­ed to turn a cor­ner af­ter some weak read­outs in the past. In­ves­ti­ga­tors in May re­port­ed that two of three co­horts con­tin­ued to re­spond to treat­ment, with the ma­jor­i­ty still free of the need for res­cue in­jec­tions, while the third co­hort ex­pe­ri­enced few­er side ef­fects than oth­er an­ti-VEGF ther­a­peu­tics.

Lau­rent Fis­ch­er

The year 2019 was more dif­fi­cult for the biotech. In April of that year, the FDA im­posed a clin­i­cal hold on the ap­pli­ca­tion to test AD­VM-022 in hu­mans, ask­ing Ad­verum for more da­ta on the chem­istry, man­u­fac­tur­ing and con­trol process, End­points News re­port­ed. The hold was lift­ed short­ly af­ter.

Then in Sep­tem­ber, Ad­verum re­vealed da­ta that in­di­cat­ed pa­tients with AMD saw their vi­sion de­te­ri­o­rate when treat­ed with AD­VM-022, de­spite signs that the treat­ment was im­prov­ing reti­nal anato­my. Those pa­tients who saw a vi­sion de­te­ri­o­ra­tion lost vi­su­al acu­ity by two let­ters on av­er­age in a 90% con­fi­dence in­ter­val of -9.1 let­ters to +5.1 let­ters, the com­pa­ny re­port­ed from the 24-week OP­TIC tri­al.

In late 2019, the biotech al­so aban­doned de­vel­op­ment of its then-lead ex­per­i­men­tal drug, AD­VM-043, for treat­ing A1AT de­fi­cien­cy.

In a press re­lease an­nounc­ing Ad­verum’s new fa­cil­i­ty, CEO Lau­rent Fis­ch­er was down­right bull­ish on the com­pa­ny’s fu­ture.

“We are build­ing a team with ex­cep­tion­al AAV-gene ther­a­py ex­pe­ri­ence and we are thrilled to join the high­ly-skilled and di­verse North Car­oli­na biotech com­mu­ni­ty,” he said. “This state-of-the-art fa­cil­i­ty will sup­port our com­mer­cial­iza­tion of AD­VM-022, the po­ten­tial first mass mar­ket­ed gene ther­a­py for wet AMD and DME.”

While Boston and San Francisco are the unquestioned leading biotech hubs in the US, drugmakers — particularly contract manufacturers — are looking elsewhere for cheaper real estate and untapped potential. Now, a San Diego-based biologics maker looking to rapidly scale up is setting down roots in North Carolina.

CDMO Abzena will add 325 jobs in Sanford, NC, as part of a $200 million biologics plant that will eventually house around 24,000 square feet of bioreactor capacity, the company said.

Where other companies have gone big, Avrobio is going small. Its manufacturing operation is no different.

Instead of trying to keep up with the validation of new facilities — and spending money and precious time in the process — the company has opted for a different approach: small, automated pods that can be installed in rented clean rooms anywhere. Though production output isn’t as high as other companies, Avrobio avoids brick-and-mortar and is able to stay flexible and nimble to respond to fluctuations.