Days ago when Deer­field part­ner Bruce Gold­smith jumped to helm Pas­sage Bio, he cit­ed a few rea­sons why it’s an “ex­treme­ly ex­cit­ing time” to be join­ing the gene ther­a­py play­er: IND fil­ings for three lead pro­grams, a da­ta-rich 2021 and an ex­pand­ing pipeline of ex­per­i­men­tal drugs for rare, mono­genic CNS dis­eases.

Bruce Gold­smith

It turns out there’s one more rea­son he held back: The Philadel­phia-based start­up was prep­ping an IPO.

Pas­sage Bio has pen­ciled in $125 mil­lion for its pub­lic de­but on the Nas­daq, with the ma­jor­i­ty of the pro­ceeds go­ing to the three AAV-based prod­uct can­di­dates slat­ed to en­ter the clin­ic in 2020.

Here’s the break­down on the tech be­hind each of them — of­fer­ing a glimpse of the ar­se­nal of de­liv­ery tools co-founder Jim Wil­son has as­sem­bled over the decades:

1. PBGM01 uti­lizes a next-gen­er­a­tion AAVhu68 cap­sid to de­liv­er to the brain and pe­riph­er­al tis­sues a func­tion­al GLB1 gene en­cod­ing lyso­so­mal be­ta-galac­tosi­dase, or b-gal, for in­fan­tile GM1 gan­gliosi­do­sis
2. PBFT02 uti­lizes an AAV1 cap­sid to de­liv­er to the brain a func­tion­al GRN gene en­cod­ing pro­gran­ulin, or PGRN, for FTD caused by pro­gran­ulin de­fi­cien­cy, or FTD-GRN
3. PBKR03 uti­lizes a next-gen­er­a­tion AAVhu68 cap­sid to de­liv­er to the brain and pe­riph­er­al tis­sues a func­tion­al gene en­cod­ing the hy­drolyt­ic en­zyme galac­to­syl­ce­rami­dase, or GALC, for in­fan­tile Krabbe dis­ease

There are some com­peti­tors work­ing on each of the dis­eases they are tack­ling, in­clud­ing Ax­o­vant and Lyso­gene for GM1 as well as Alec­tor and Pre­vail for FTD, but Pas­sage Bio was con­fi­dent about be­ing an in­te­grat­ed play­er ca­pa­ble of tack­ling mul­ti­ple “cross-cor­rec­tion­al ther­a­pies” in the CNS.

Wil­son, a well-re­spect­ed pi­o­neer in the gene ther­a­py field, had in­tend­ed for this to be his lega­cy com­pa­ny, Or­biMed part­ner Stephen Squin­to pre­vi­ous­ly told End­points News. Thanks to Wil­son’s con­nec­tion at the Uni­ver­si­ty of Penn­syl­va­nia, Pas­sage se­cured a li­cens­ing deal with the uni­ver­si­ty for an up­front of just $2.5 mil­lion in cash and 3,720,000 shares in stock (then val­ued at $0.9 mil­lion) — plus a promise to fund cer­tain pre­clin­i­cal ac­tiv­i­ties, the S-1 re­vealed.

The pact cov­ered rights to 12 ther­a­pies in to­tal, and should Pas­sage ex­er­cise those op­tions by the 2022 ex­piry date, up­front fees would be some­where be­tween $0.8 mil­lion to $1 mil­lion. They have al­ready made the call on six; Penn is el­i­gi­ble for up to $16.5 mil­lion in de­vel­op­ment mile­stones and $55 mil­lion in sales mile­stones for each.

That, plus the $10 mil­lion up­front Pas­sage paid Catal­ent’s Paragon sub­sidiary for man­u­fac­tur­ing work, amount­ed to the bulk of the biotech’s ex­pense. While it’s bagged two hefty megarounds, Pas­sage has on­ly burned through $58.7 mil­lion so far.

The syn­di­cate stayed ba­si­cal­ly the same through­out Se­ries A and B, fea­tur­ing Fra­zier Life Sci­ences (13.9%, rep­re­sent­ed by Wil­son’s long­time men­tor Tachi Ya­ma­da on the board), Or­biMed (19.6%), Ver­sant Ven­tures (14.8%) Lil­ly Asia Ven­tures (7.6%), New Leaf Ven­tures (7.0%), Vi­vo Cap­i­tal (7.0%) and Ac­cess In­dus­tries’ AI Pas­sage (6.5%). Wil­son re­tained 7.0% for him­self.

With his rare dis­ease ex­pe­ri­ence gleaned from years at Alex­ion, Squin­to ini­tial­ly took up the CEO role be­fore pass­ing the reins to Gold­smith. His com­pen­sa­tion pack­age for the past year to­taled $2.2 mil­lion com­pen­sa­tion, and he con­tin­ues to be part of the team as in­ter­im head of R&D.

Chief tech­ni­cal of­fi­cer Alex Fo­topou­los and chief med­ical of­fi­cer Gary Ro­mano re­ceived $2.25 mil­lion and $2.02 mil­lion, re­spec­tive­ly.

Over the past few years, the promise of blocking CD47 — a “don’t eat me” signal co-opted by cancer cells — has sent drugmakers big and small into a frenzy. But one biotech is now bowing out.

Zai Lab is deprioritizing ZL-1201, its CD47 inhibitor, scrapping plans for a Phase II trial. It will now “pursue out-licensing opportunities,” the company said in its Q2 update. The decision was based on a review of the competitive landscape, it added, without going into further details.

Less than a week after HHS Secretary Xavier Becerra declared monkeypox a national health emergency, reports have emerged that the US plans to extend its vaccine supply by opting for a different route of administration.

Officials are expected to call for intradermal injection of Bavarian Nordic’s Jynneos vaccine — the only shot approved specifically for monkeypox in the US — as opposed to subcutaneous injection, unnamed sources told both the New York Times and Washington Post on Tuesday.

The FDA’s Center for Drug Evaluation and Research on Tuesday released a warning letter sent last week to Amazon CEO Andy Jassy in Seattle for selling mole removal products over-the-counter, or, as the FDA explains, “introducing, delivering, or causing the introduction or delivery into interstate commerce of products that are unapproved new drugs.”

“There are no over-the-counter (OTC) drugs that can be legally sold for mole or skin tag removal, and FDA has safety concerns about drugs marketed OTC directly to consumers for these uses,” the agency said in its Aug. 4 warning.