Signal Pharmaceuticals Inc. announced that it has completed its firstround of venture financing, raising a total of $6.1 million. The sumincludes $2.7 million in seed funding with which the company waslaunched in May 1993.

Investors in this round were Accel Partners, Venrock Associates, andKleiner, Perkins, Caufield & Byers. Harry Hixson, former president ofAmgen Inc., is also a leading investor in Signal, the company said.Only Venrock Associates was new to this latest financing round;other investors also provided seed funding for the San Diegocompany.

Signal will be headed by Alan Lewis, former vice president ofresearch at Wyeth-Ayerst Laboratories, a division of American HomeProducts Corp. Lewis joined Signal last week as president.

The company initially will seek to exploit two basic technologies,Lewis told BioWorld. Signal hopes to develop new gene transcription-based therapies through the development of small molecules thatactivate or inhibit certain transcription factors, including NF kappa Band AP1.

These factors are "clearly implicated in the initiation of inflammatorycytokine cascade," Lewis said. By finding agents that neutralize thetranscription factor that communicates between RNA and DNA, thecompany hopes to block the production of cytokines such as IL-1, IL-6 and tumor necrosis factor. Lewis distinguished this approach fromattempts to find agents that block the receptors of these proteins, astrategy being followed by other companies.

Excess production of these cytokines is implicated in a number ofdiseases, including rheumatoid arthritis and osteoarthritis, as well assepsis and inflammatory bowel disease, Lewis said. The companyalso intends to develop therapies for other inflammatory, viral andneurological diseases.

Signal also has rights to a technology patented by Fred Gage, aprofessor in the department of neurosciences at the University ofCalifornia, San Diego (UCSD), and a scientific founder of Signal.According to Lewis, Gage has found a method of maintaining a broadrange of cells and neurons in culture in such a way that theymultiply -- even if they do not do so in the body. The technology hasbeen proven for rodents, according to the company, and is now beingtested for humans.

This technology could be used for developing assay models toevaluate gene transcription modulating agents, Lewis noted, butcould also be used to evaluate the functional activity of neurons, inpotential transplant applications, or in effecting gene transfer to cellsthat do not normally divide to express a desired gene. "Truthfully,we're not sure what we'll look like in a year's time," said Lewis.While he asserted that the company will "aggressively exploit" bothof its proprietary technologies, he acknowledged that a year ofscientific discovery might reorient the company's therapeutic goals.

Signal was founded last May by Mark Carman, formerly manager ofnew product planning at Athena Neurosciences Inc. and currentlySignal's vice president of corporate development. In addition to Gage,the company's scientific founders include Michael Karin, professor ofpharmacology at UCSD, and Inder Verma, a professor in themolecular biology and virology laboratory at The Salk Institute in LaJolla, Calif.

Gage and Verma were also both scientific founders of GenesysTherapeutics, a gene therapy company that was headed by Hixsonbefore it merged with Somatix Therapy Corp. in 1991.

-- Karl A. Thiel Associate Editor

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