James M. Wilson, MD, PhD, director of the Gene Therapy Program at the University of Pennsylvania, and a co-founder of Passage Bio.

Passage Bio has yet to spell out how much in net proceeds it expected to generate—which would depend on how much money the company agrees to raise in the IPO—or how much it would set aside toward the purposes outlined in its S-1 registration statement, filed Monday.

“We intend to use the net proceeds that we receive in this offering to advance our lead products in clinical trials, to advance our discovery and candidate selection stage programs, and for general corporate purposes,” Passage Bio stated in its preliminary prospectus.

Headquartered in Philadelphia, Passage Bio was formally launched with $115.5 million in Series A financing in February 2019—and plans for developing five therapeutic candidates that incorporate adeno-associated virus (AAV) technologies developed by Wilson and colleagues at the University of Pennsylvania (Penn) and its Gene Therapy Program (GTP).

Three of those five programs are now in IND-enabling phases and slated to begin clinical development later this year. During the first half of 2020, the company plans to submit an IND for PBGM01, designed to treat GM1 gangliosidosis by targeting the lysosomal enzyme β-galactosidase (GLB1). Passage Bio said it expects to launch a Phase I/II trial for PBGM01 in the second half of 2020, and anticipates clinical data to be available in the first half of 2021.

Passage Bio plans IND filings during the second half of this year, followed by the launch of Phase I/II trials in the first half of 2021 for two other programs: PBFT02, designed to treat frontotemporal dementia by targeting the gene encoding the lysosomal protein progranulin (PGRN); and PBKR03, aimed at treating Krabbe disease by targeting the gene encoding the hydrolytic enzyme galactosylceramidase (GALC).

Clinical data for both candidates is expected in the second half of 2021.

For its initial clinical trials, Passage Bio said, it will rely on Catalent’s Paragon Gene Therapy unit—the companies signed a manufacturing agreement in July 2019—for supply of its product candidates, and on Penn to manage the transfer of technology to Paragon that is necessary for production.

“We expect to establish our own manufacturing facility for long-term commercial market supply,” Passage Bio added.

Preclinical MLD, ALS, CMT2A programs

The company has three other preclinical programs in the discovery or candidate selection stage:

  • PBML04 for metachromatic leukodystrophy (MLD) patients who have mutations in the ARSA gene;
  • PBAL05 for amyotrophic lateral sclerosis (ALS) patients who have a gain-of-function mutation in the C9orf72 gene;
  • PBCM06 for Charcot-Marie-Tooth Type 2A (CMT2A) patients who have a mutation in the MFN2 gene.

Through its research collaboration with GTP, Passage Bio also has the option to license programs for six additional rare, monogenic CNS indications through 2022.

“We are purposefully focusing on rare, monogenic CNS disorders for which we believe our genetic medicine approach provides distinct technical advantages based on decades of research by GTP,” Passage Bio declared. “Our vision is to become the premier genetic medicines company by developing and ultimately commercializing therapies that dramatically and positively transform the lives of patients suffering from life-threatening CNS disorders with limited or no approved treatment options.”

Overseeing that vision day-to-day is the task of Passage Bio’s new CEO Bruce Goldsmith, PhD, whose appointment the company announced on January 28. Goldsmith was previously a venture partner responsible for early-stage investments at Deerfield Management, as well as interim CEO of Civetta Therapeutics since April 2019. At Passage Bio, Goldsmith succeeded interim CEO Stephen Squinto, PhD, who became acting head of R&D and remains on the company’s board of directors.

Passage Bio finished 2019 with a net loss of $45.6 million, on top of the $12.8 million net loss reported for 2018. The company said it has cash and cash equivalents of $158.9 million as of December 31, 2019.

Passage Bio licensed the CMT2A program from Penn and GTP in September 2019. That month, the company also completed a $110 million Series B financing, boosting its total capital raised to $225.5 million.

The company has attracted investments from OrbiMed Advisors, Versant Ventures, Frazier Healthcare Partners, Access Biotechnology, Lily Asia Ventures, New Leaf Venture Partners, Vivo Capital, and Boxer Capital of Tavistock Group, among others.

The largest ownership stake—27,764,440 shares or 19.6%—is held by OrbiMed, whose founding partner and co-head of Global Private Equity Carl Gordon, PhD, CFA, is a board member of Passage Bio. Gordon has told the company he will resign from its board effective immediately prior to launch of the IPO, Passage Bio stated.

Upon the completion of the IPO, Passage Bio’s authorized capital stock will consist of 300 million shares of common stock, and 10 million shares of undesignated preferred stock.

The post Gene Therapy Developer Passage Bio Files for $125M IPO appeared first on GEN – Genetic Engineering and Biotechnology News.