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Biotech / Medical : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?

To: Machaon who wrote (19145)	4/17/1998 10:42:00 AM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Bob, LGND actually has a program with LLY that includes LLY SERMs such as Evista. There are really two breast cancer markets. One is prevention and the other is treatment. LGND has already shown Panretin and Targretin to be effective in prevention models and Targretin has been shown to be very effective in treatment models. In clinical trials, LGND and its partners are very active. I believe that the upcoming presentation (at ASCO next month) will show that women treated with Evista for osteoporosis had a lower breast cancer incidence than those treated with the placebo. However, there will probably be many breast cancer prevention approaches. The recent tamoxifen prevention trial was a landmark study showing that like rats, it was possible to prevent breast cancer in women. However, the result certainly did not indicate that breast cancer would be eliminated. It is not even clear who will take tamoxifen to prevent breast cancer. The study really raised more questions than it answered. The side effects from tamoxifen are significant. In fact the mortality rates between those taking Tamoxifen and those taking a sugar pill were virtually identical. Five women taking the placebo died from breast cancer. However, five women taking Tamoxifen also died, three from breast cancer and two from blood clots in their lungs. Although the Tamoxifen trial was halted early, there are still many unanswered questions. For treatment, Tamoxifen use beyond 5 years has not been shown to produce any benefit. Thus, its not clear when women should begin taking Tamoxifen for chemoprevention or even if the same 5 year limit for treatment also applies to prevention. Investigators know that there is much room for improvement. Consequently, those in the trial who randomly received the placebo will not be offered Tamoxifen. Instead they will be offered enrollment in another prevention trial and they will be randomly assigned Tamoxifen or Evista. Evista is one of many SERMs with potential for breast cancer prevention. Recently, one of LGND's patners, PFE, elected to discontinue the registration process for Droloxifene treatment of breast cancer. Instead they chose to switch the compound into a breast cancer prevention trial. Similarly, they have another LGND selected compound, CP-366,156, in trials for osteoporosis and this compound may also have breast cancer prevention uses. Other SERMs in osteoporosis prevention trials include SBH's Idoxifene and LGND's partner AHP's TSE424. These compounds may also have prevention applications for breast cancer. LGND's retinoids and rexinoids (Panretin and Targretin) have also generated positive chemoprevention data in rat models. Moreover they synergize with Tamoxifen (and probably synergize with the other SERMs mentioned above). Consequently, both compounds could be used as mono or combination therapy for the prevention of breast cancer. In addition to prevention, the SERMs and rexinoids have treatment potential. Tamoxifen is the hormonal treatment of choice for breast cancer in humans. LGND has shown that Targretin is superior to Tamoxifen in the rat model and it also synergizes for treating the breast cancer. In the clinic Targretin is in advanced trials for treating breast cancer as monotherapy. Panretin is in advanced trials for treating as monotherpy as well as combination therapy with Tamoxifen. LGND also has a research program with LLY to identify second generation combinations (of SERMs and Rexinoids). The entire field is very young. LGND is well positioned in SERMs as well as Rexinoids. Positive human data with any of the above should translate into positive news for LGND.