Advanced Therapies Inc., which is developing a non-viral drugcarrier technology, entered into its first corporate collaboration.

Sandoz Ltd. subsidiary Genetic Therapy Inc. (GTI) agreed to payAdvanced Therapies up to $11 million in research support andmilestone payments to apply the latter's Artificial Viral Envelopetechnology to the delivery and targeting of GTI's gene therapyprograms. The collaboration will focus on products for cancer andpulmonary disease.

The Artificial Viral Envelope (AVE) mimics the form and function ofnatural viral envelopes, which are able to target and enter specificcells. AVEs are synthetic, lipid-based carriers designed to carrytherapeutic agents.

"We have the synthetic lipid-based system and [GTI] has all theexpertise with viral systems," said Hans Schreier, principal scientistat Advanced Therapies and inventor of the AVE technology."Hopefully we can come up with new systems that will utilize thegood performance characteristics of both systems."

Schreier said one goal is to engineer out the unwanted components _such as those that result in inflammatory and immune responses.

"We want to develop the technologies, not just utilize components ofeach other's technologies," Schreier said. "This is a true developmentprogram, not just a manufacturing relationship where we would justpackage something for them."

Advanced Therapies, of Novato, Calif., was incorporated in 1993 andreceived its first financing late in 1994. Calvert Social VenturePartners, of Bethesda, Md., was the original investor and El DoradoVentures, of Cupertino, Calif., led additional financing.

Schreier invented the AVE technology while at the University ofFlorida in Gainesville. Advanced Therapies got an exclusive licensefrom the university to issued and pending patents on AVEmanufacturing, composition and delivery uses.

The deal with Genetic Therapy, of Gaithersburg, Md., is for at leasttwo years. Schreier said it entails an up-front payment, researchsupport and milestones that could total about $11 million. No equitycomponent is included. Advanced Therapies also would be entitled toroyalties on resulting products.

GTI, bought out in July 1995 by Basel, Switzerland-based Sandoz,has exclusive worldwide marketing rights to any products developedfrom the collaboration.

The AVE technology is based on the idea that the membrane thatenvelopes most viruses contains the information for targeting andentering specific cells. That envelope contains proteins that recognizeand attach to discrete cell surface receptors, and lipids that facilitatefusion with cell membranes and entry into the cell.

AVEs have been constructed to mimic the form and function ofnatural viral envelopes and contain proteins and lipids in the samecomposition. Within the AVE can be carried drugs, peptides andproteins, and DNA constructs for gene therapy.

Advanced Therapies already has constructed AVEs to model the viralenvelope of HIV, including gp160 targeted to CD4 T lymphocytes;respiratory syncytial virus surface protein to epithelial cells;kininogen peptide to endothelial cells; and malarial circumsporozoitepeptide to hepatocytes. Transfection and bioactivity, the companysaid, have been demonstrated in both in vitro studies of cell uptakeand in animal studies. No toxicity was seen in preliminary studies ofsingle doses of empty AVEs.

Schreier said Advanced Therapies plans to enter additionalcollaborations much like the one formed with GTI. "What's uniqueabout this system is that it can be very selective for target areas," hesaid. n

-- Jim Shrine

(c) 1997 American Health Consultants. All rights reserved.