Pervasis Therapeutics announced that they have raised $9.75M to further develop their allogenic tissue engineered endothelial cell (EC) product for vascular health indications. Their Vascugel product is comprised of ECs grown in 3D collagen sponges that are implanted externally on blood vessels to prevent them from occluding. Pervasis has proven safety in a Phase I study concluded in 2006, and they have recently finished enrollment of two end stage renal disease (ESRD) Phase II studies in 2007. Pervasis will use the new cash to further develop an injectable version of Vascugel, as well as extend the technology into peripheral and coronary vascular indications in 2008. Now that they have their base safety data, new trials should have lower hurdles for iniation. Pervasis has the benefit of a star-studded (in the technology sense anyway) board and advisory panel, which includes Bob Langer, Joseph Vacanti, and Alazar Edelman – 3 top MIT/Harvard serial technology spinnout experts. This helps with fundraising but not necessarily clinical efficacy, which is the true value driver.

The Pervasis technology has actually been around for over 10 years. Vascugel was originally licensed by Reprogenesis where Dr. Helen Nugent (a co-founder of Pervasis) started her biotech career. The technology didn’t make it when Reprogenesis merged with Creative Biomolecules and Ontogeny to form Curis, and judging from Dr. Nugent’s affiliations on publications, she went back to MIT (at least for awhile) to further develop this technology in Edelman’s lab. Pervasis was formed in 2003 and they have emerged as a company focused on this single vascular health technology. The team has enhanced and optimized the technology over the last several years and journal articles can be found at the Pervasis web site that describe the science.

Their most recent publication gives a glimpse into their manufacturing strategy. This includes:

1. growing up sufficient ECs in flasks,
2. seeding these cells onto Gelfoam (pig collagen) scaffolds, and then
3. growing the ECs on the Gelfoam until the the ECs grow to a certain density within the scaffolds (see above graphic).

The manufacturing process in the manuscript seems a little complex and the quality control (QC) assays too extensive. First, the EC/collagen constructs are periodically analyzed for cell counts to determine when the constructs are ‘ready’, meaning they need to sacrifice product for testing. Not ideal. It would be nice to be able to qualify a process where some non-invasive method (alamar blue, oxygen consumption) could be used to establish EC confluence with the sponges. Secondly, they test for several biological activities that they argue are potential mechanisms for why the ECs work. While this makes nice science, it complicates the QC strategy. It is really best to just focus on one or two, to make sure that you are not tied in to all 5 assays as release criteria upon BLA. Why pay for 5 expensive assays when one will get you to where you need to go at 20% of the costs? They also culture in the presence of serum (as most cell therapy companies do), and it will be interesting to understand how they wash or rinse their product prior to human use. The other question is around the stability of the product. Are they cryopreserving the cells in the Gelfoam (not in publications), or is Vascugel a fresh product that has a finite (days to weeks) shelf-life once harvested? These are very important issues to address, as the FDA expects you to have a locked down process and strategy once you start Phase III trials, which they might not be too far away from.

Pervasis should be getting initial data from their closed Phase II trials this year. According to the trial design found at clinicaltrials.gov, it looks like they have a 6 month endpoint with 2.5 years of extended follow-up. Assuming positive results (and that my time-frame assumptions are correct), this would allow them to justify initiation of a Phase III trial in 2009. Things to track in the next year will be 1) what new indications they test clinically, 2) if they can get the injectable Vascugel product working as good at the Gelfoam-based product, and 3) if they can initiate a trial based on the injectable product technology.