A company developed to commercialize work in the area of naturallyprocessed peptides discovered at Harvard University secured its firstround of venture financing.

Pangaea Pharmaceuticals believes the approach has applications inviral infections and cancer by stimulating the immune system and inautoimmune diseases by down-regulating the T cells. The companyuses a delivery system called Biotopes, which are small circularpieces of DNA encoding a particular peptide and the signals thatprovide for their intracellular trafficking.

Pangaea was founded in 1992 to house the work coming from theHarvard scientific founders: Roman Chicz, Mary Lynn Hedley,Robert Urban and Jack Strominger. The business founders were TerriChernick, Neupogen product manager at Amgen Inc., of ThousandOaks, Calif. and J. Thomas Hexner, a founder of Cambridge, Mass.-based Genetics Institute Inc.

Pangaea raised $3.25 million in Series A financing led by MedicalScience partners, of Wellesley, Mass., and Walden, of San Francisco.Proceeds will go toward setting up a laboratory and offices inCambridge, Mass., and to fund ongoing preclinical work.

The work sprung from scientists' ability to identifyimmunomodulatory peptides from major histocompatibility complex(MHC) molecules, the receptors that communicate to T cells. Inresearching the receptors, they started "knocking out" the actualpeptides that were in the groove, or mouth, of the molecules,Chernick said. The researchers were able to knock out both antigenicpeptides, such as virus particles, and self-peptides, which normallyare non-immunogenic but can cause inflammatory responses whenmistakenly identified as foreign.

The peptide sequences, since they are derived from the naturallyprocessed peptides, represent the exact information antigenpresenting cells use naturally to communicate with T cells. TheBiotopes precisely fit MHC molecules, and are delivered to the MHCassembly site of the cell. Together those features could provideincreased potency and efficiency.

"We would use the peptides themselves as therapeutics butsubstantial research has shown peptides are inadequate because theyrapidly degrade in the blood and don't readily exchange withnaturally processed peptides," Chernick said. Pangaea overcomesthose problems using an "inside-out" DNA approach, which uses thecell's own machinery for producing the desired peptide.

The company has more than 400 MHC bound peptides in its database of epitopes. The DNA-based in vivo expression system(Biotopes) empowers antigen presenting cells with the ability tosynthesize large amounts of a specific peptide.

Peptides derived from tumor antigens or pathogenic organisms wouldactivate a specific immune response. Expression of a Biotopeencoded inert self-peptide by antigen presenting cells preventsbinding of autoreactive peptides.

The company said an advantage of delivering a naturally processedpeptide vs. an entire immunogenic protein is that only the relevantinformation needed for a response is expressed. In addition, theBiotopes do not integrate into the genome, alleviating some of theconcerns with other DNA-based therapeutics.

Pangaea's first viral target will be human papilloma virus, which canlead to cervical carcinoma. The company expects to have animal databy the end of the year. Other viral targets include genital warts,hepatitis B and C, herpes and HIV.

For autoimmune diseases, the company has in vitro and preliminarymice data showing the ability to down-regulate an up-regulatedimmune process. Data from diseased animal models of myastheniagravis and multiple sclerosis are expected by the second quarter of1997. Pangaea is in the early stages of applying the technology to theHER2/neu oncogene for application in breast and ovarian cancers. n

-- Jim Shrine

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