The Allergan-Ligand joint venture has filed its firstinvestigational new drug (IND) application for the use of 9-cis-retinoic acid compound LGD1057 as an oral therapy for cancer,the companies announced Monday.

The developmental milestone has also triggered a number ofchanges in the terms of the original agreement between thetwo companies, including a realignment of product rights andan additional equity investment in Ligand by Allergan.

Ligand Pharmaceuticals Inc. of San Diego joined forces withAllergan Inc. of Irvine, Calif., in July 1992 to develop andcommercialize pharmaceutical products based on retinoidtechnology. Retinoids are naturally occurring hormones that arechemically related to vitamin A. They are known to havemarked biological effects on a wide variety of cell types,mediated by their selective binding to intracellular receptors.

Ligand brought to the joint venture its receptor technology andAllergan brought its vast collection of retinoids.

And 9-cis-retinoic acid is the first new endogenous non-peptide hormone discovered in more than 23 years, accordingto David Robinson, president and chief executive officer ofLigand. In preclinical tests, the particular retinoic acid analogLGD1057 has been shown to inhibit cell proliferation andinduce apoptosis (programmed cell death) and celldifferentiation.

The Allergan-Ligand alliance was formed as a 50-50 jointventure, with each company splitting all research, developmentand commercialization costs, as well as any earnings fromretinoid products resulting from the venture.

Initially, both companies agreed to provide $5 million per yearfor three years to fund the venture. But they were soencouraged by the progress of the R&D program that they havedecided to increase that funding in 1994 (the amount, however,is undisclosed).

Allergan (NYSE:AGN) has also opted to exercise its warrant for400,000 shares of Ligand stock (300,000 class C shares and100,000 class A shares), thus adding another $4 million toLigand's (NASDAQ:LGNDA) coffers and increasing its sharesoutstanding to about 14.5 million, explained Susan Atkins,Ligand's vice president of corporate communications.

By exercising the warrant, Allergan also increased its equitystake in Ligand to 14.6 percent. Allergan's equity had been12.2 percent, amassed as the result of its $20 millioninvestment in the joint venture and its $7.5 million stockpurchase (together with Glaxo Inc.) during Ligand's initialpublic offering (in November 1992).

While the Ligand-Allergan joint venture is ready to enter theclinic with retinoid compound LGD1057, the companies havedeveloped a number of others as well. They have decided tochange their rights regarding compounds LGD1069 andAGN190168. Ligand has reclaimed its worldwide rights toLGD1069, systemic and topical, while Allergan has reclaimed itsworldwide rights to systemic applications of AGN190168, acompound for which Allergan already has the topical rights.These rights will be exercised outside the joint venture.

-- Jennifer Van Brunt Senior Editor

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