Two Ligand Pharmaceuticals Inc. compounds targetingintracellular retinoid receptors involved in cell growth,differentiation and apoptosis, have shown positive PhaseI/II results for AIDS-related Kaposi's sarcoma, the SanDiego-based company said.

One compound, ALRT 1057, is being developed under ajoint venture between Ligand and Allergan Inc., of Irvine,Calif. In December 1994, the two formed a company,Allergan Ligand Retinoid Therapeutics Inc. (ALRT), tofund research on retinoid-based drugs. The othercompound, Targretin (LGD1069), is owned by Ligandalone. Both drugs are being tested in topical forms forKaposi's sarcoma, which is characterized superficially byskin lesions.

Ligand officials said Friday the interim data from thetrials of the two drugs were so encouraging that FDAapproval could come in two years.

The compounds are derived from retinoids, which arenaturally occurring hormones chemically related tovitamin A and are known to affect cell activities throughbinding to intracellular receptors. ALRT 1057, a syntheticversion of 9-cis-retinoic acid, binds to six intracellularreceptor types, which are divided into two subfamilies ofthree each called RARs and RXRs. Targretin is asynthetic compound designed to bind only to RXRs.

The compounds are being evaluated in two separate on-going Phase I/II trials. Patients had at least four lesions.Two lesions were treated with the drugs and two receivedno treatment.

Robert Stein, Ligand's chief scientific officer, said thecompounds are believed to interfere with cancer cellgrowth and may induce programmed cell death, orapoptosis.

In the ALRT 1057 studies, 44 patients have beenenrolled. Results released last week were for 20 patientstreated for eight weeks or longer. Of the 59 lesionsreceiving the drug, 7 percent were cleared and 37 percentshowed partial responses. In the untreated group oflesions partial responses were seen in only five percent.No untreated lesions were cleared.

In the Targretin trials, 57 patients have been enrolled and23 of them were evaluated after eight weeks. Of 64lesions treated, 5 percent were cleared and 23 percentshowed partial responses. Three percent of untreatedlesions showed responses and half were cleared.

Stein said more patients will be enrolled in the trials andadditional efficacy data will be collected to supportsubmissions for approval in the U.S. and Canada.Because no current topical treatment is available forKaposi's sarcoma, he speculated the compounds couldget FDA approval by 1997.

Oral forms of both compounds also are in clinical trials ina variety of cancers, including visceral manifestations ofKaposi's sarcoma.

Ligand's stock (NASDAQ:LGND) closed Friday at $9.88unchanged. Allergan (NYSE:AGN) was up 38 cents to$33.88. ALRT (NASDAQ:ALRIZ) ended the day at $16unchanged. n

-- Charles Craig

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