Apollon Inc., which has the first DNA-based geneticvaccine directed at AIDS in the clinic, is potentiallygetting more than $100 million through a collaborationwith Wyeth-Ayerst Laboratories.

The deal covers Apollon's Genevax-HIV product, whichis in Phase I/II testing, and a similar product beingdeveloped for herpes simplex virus and human papillomavirus (HPV). A provision of the agreement allows Wyeth-Ayerst to expand the collaboration to include othermicroorganisms.

Apollon, of Malvern, Pa., was formed in 1992 byCentocor Inc. and venture capitalists. Vincent ZurawskiJr., a co-founder of Malvern-based Centocor, started thenew company and is its president and CEO.

Apollon's technology is designed to stimulate bothantibodies and cytotoxic T cells, unlike recombinantprotein vaccines or those consisting of inactivatedpathogens, which do not trigger killer T cell production.A facilitating agent, the local anesthetic bupivacaine, hasbeen shown to enhance DNA uptake and gene expression.

Specific terms of the deal were not disclosed. Generally,however, it involves research and development fundingand developmental milestones. Apollon wouldmanufacture any products, and sell them to Wyeth-Ayerstfor worldwide distribution.

"If we advance these programs ahead towardcommercialization, we will see payments that totalgreater than $100 million," Zurawski said. "The deal isquite substantial. The real issue is we have an importantdeal that has both milestone payments and committedfunds, and we're moving ahead in a very aggressivefashion."

Last June the vaccine was injected into its first patient,who then became the first person ever to be inoculatedwith a vaccine based on viral genes rather than theproteins those genes encode. (See BioWorld Today, June19, 1995, p. 1.) That Phase I/II study called for enrollmentof 15 more patients, after the first was evaluated in detail,to gather mostly safety and immune response data.

Zurawski, while not disclosing the enrollment status, saidthere have been no adverse effects, local reactions at theinjection site, or laboratory abnormalities seen in thoseinjected thus far.

The prototype vaccine is a genetically engineeredconstruct consisting of HIV genes that encode the viralenvelope protein, gp 160, along with the rev gene, whichincreases expression of the gene. Apollon has beencollaborating on its development with David Weiner, aUniversity of Pennsylvania Medical School associateprofessor and director of the university's Institute ofBiotechnology and Advanced Molecular Medicine.

The company said the vaccine should produce selectedHIV proteins in the cells of the person vaccinated. Thenewly synthesized proteins then provoke an immuneresponse against the selected viral proteins, and arecharacterized by production of antibodies and killer Tcells. In addition, the selective immune response shouldbe stimulated without an increase in the rate of HIVreplication by the infecting virus.

There has been skepticism that injected DNA consistentlycould support levels of gene expression. That's where thefacilitating agents come in.

Among the advantages cited for the Genevax vaccines arethat the genes for several antigenic proteins of thetargeted pathogen can be combined in one vaccine; that invivo expression of genes produce proteins more similar tonative pathogens; and the plasmid vectors for thedifferent products are similar, allowing for easierdevelopment and manufacture.

Zurawski said both therapeutic and prophylacticapplications of the vaccines will be evaluated, and areincluded in the deal. The herpes and HPV vaccines, alsoDNA-based, are expected to enter clinical trials in thecoming months, Zurawski said.

In the herpes vaccine, for example, one of the targets isthe envelope protein glycoprotein D. The genes forseveral additional protein targets will be evaluated forherpes and HPV, and one or a combination of them willbe taken into the clinic, Zurawski said.

Wyeth-Ayerst, a Radnor, Pa.-based division of AmericanHome Products Corp., has a vaccine focus, which wasaccentuated with the merger of Wayne, N.J.-basedLederle-Praxis Biologicals (formerly an AmericanCyanamid Corp. company) into Wyeth-Ayerst. Zurawskisaid the partner's expertise had been beneficial.

One example he provided was the contribution by Wyeth-Ayerst of certain genetic material that was a valuable partof bringing one of the programs forward. Wyeth-Ayerstofficials could not be reached for comment.

"Our business strategy will be to develop some productsindependently," Zurawski said. "We've had someprograms that have been the result of certain molecularbiology research, which have led to potential targets forsmall molecule programs. But our primary goal with thecompany now is to commercialize the Genevaxtechnology, and follow that up with application of DNA-facilitated technology to the gene therapy field."

Additional Genevax product targets are T cell lymphoma(which may be in human studies this year), viral hepatitis,tuberculosis, certain cancers and autoimmune diseases.The company has raised more than $14 million since itsfounding in 1992. Centocor owns about one-third of thecompany, and venture capital groups and Apollonemployees own the rest. n

-- Jim Shrine

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