TorreyPines Therapeutics Inc. laid out a plan for 2008 that includes cutting costs, advancing its three lead product candidates through clinical trials and ramping up business development activities.

The La Jolla, Calif.-based company shaved an estimated $3 million to $4 million from its operating expenses by cutting 10 employees.

Among those departing is Chief Medical Officer Michael Murphy, who the company said is leaving to pursue other interests. TorreyPines reported $39.7 million in cash and equivalents as of Sept. 30, and the cuts will reduce its projected 2008 burn rate to between $22 million and $24 million.

Most of that money will go toward clinical trials of the AMPA/kainate receptor antagonist tezampanel, its oral prodrug NGX426, and the muscarinic agonist NGX267.

Tezampanel completed a Phase IIb acute migraine trial last fall, and TorreyPines plans to discuss the data with the FDA during a clinical guidance meeting slated for the first half of 2008. During a conference call, TorreyPines President and CEO Neil Kurtz acknowledged that there has been "some confusion" in the marketplace about the results of the trial but maintained that the company "does not agree" they were negative.

In the trial, the 40-mg dose of tezampanel significantly improved headache pain compared to placebo, the primary endpoint of the trial (p=0.033). The dose also resulted in a significant improvement or trend toward improvement for several secondary endpoints such as later pain relief, disability, light sensitivity, nausea, vomiting and various composite measures. Yet the 70-mg and 100-mg doses of tezampanel did not achieve statistical significance for the primary endpoint, leading to questions regarding the drug's efficacy.

Kurtz said that the company has discussed the data with several key opinion leaders, and that "people walk away believing the drug is active and believing 40 mg is a safe dose." If the FDA agrees, TorreyPines will plan for an end-of-Phase II meeting in the second half of the year but will hold off on actually initiating a Phase III program until it finds a partner.

In the meantime, the company plans to initiate a Phase II trial of tezampanel in muscle spasticity and rigidity secondary to spinal cord trauma in the second half of the year. Positive results could expand the potential for the drug beyond pain and open the door for trials in areas like Parkinson's disease or cerebral palsy.

The company also plans to advance several clinical trials with NGX426, the oral prodrug of tezampanel. In the first half of the year, TorreyPines will complete an ongoing Phase I maximum tolerated dose trial and initiate a Phase I single dose trial in a capsaicin model for neuropathic pain. A Phase I multiple dose trial will follow in the second half of 2008.

NGX426 may be on the table for partnering discussions along with tezampanel, but Kurtz said it is premature to speculate on what a deal for the two drugs could look like or when such a deal might be expected to close.

With the muscarinic agonist NGX267, TorreyPines plans to initiate a Phase II trial in dry mouth associated with Sjogren's syndrome in the first half of the year. Data are expected toward the end of the year, and Kurtz said the company will seek a partner for the program after Phase II.

Partnering efforts also continue for Alzheimer's disease drugs phenserine, posiphen and bisnorcymserine, which TorreyPines acquired in its 2006 merger with Axonyx Inc. (See BioWorld Today, June 9, 2006.)

Additionally, the discovery phase of TorreyPines' gamma-secretase modulator collaboration with Eisai Co. Ltd. is set to end this month, and Kurtz said the two companies "could not agree to terms" to continue the partnership. All rights to the program will return to TorreyPines, which plans to seek a new partner.

Shares of TorreyPines (NASDAQ:TPTX) fell 3 cents to close at $2.12 on Thursday.