Neurobiological Technologies Inc.'s two kernels of news to pop last week - positive interim data from a partner with Xerecept for brain edema, plus a deal with the Buck Institute For Age Research to develop fibroblast growth factor-2 against Huntington's disease - failed to butter up investors, as the value of the firm stayed "inexplicably low," in the words of analyst Russell McAllister of Merriman Curhan Ford.
Trading around $3, NTI has plenty more in its basket. Hopes are particularly high among company watchers for Viprinex (ancrod), the Phase III stroke drug due to report final data in the third quarter of 2009, with interim results expected as early as the middle of next year.
Celtic Pharmaceutical Holdings L.P. offered the Xerecept data during the Society of Neuro-Oncology annual meeting in November and detailed the poster in a press release last week, noting that the efficacy of the compound for tumor-related swelling has been measured in the 20 of the first 32 patients enrolled, who got Xerecept daily for at least 20 weeks.
The compound - a synthetic preparation of the natural human peptide hormone corticorelin acetate or human corticotropin-releasing factor - proved well tolerated, with nine of the 20 patients discontinuing their dexamethasone treatment altogether. And in most of those given a reduced dexamethasone dose, steroid side effects resolved or improved. The Celtic trial is signing up patients with primary or secondary (metastatic) brain tumors who have already completed one of two Phase III trials with Xerecept, under way at 27 centers in the U.S., Canada, Australia and New Zealand.
In the fall of 2005, NTI sold Celtic the rights to Xerecept in a deal worth up to $48 million. Earlier this year, Celtic forked over the final non-contingent payment in the deal, $4 million, which brought the guaranteed fees to $33 million. The rest of the potential money (up to $15 million) would come as regulatory milestones are met, and NTI - off the hook for any further development costs - stands to collect double-digit royalties.
Celtic also said it would stop enrolling patients in an ongoing study called NTI 0302, due to slower-than-expected enrollment, and instead would kick off an imaging study, CPDS 0701, early next year to get a better idea of Xerecept's efficacy and safety by trying to confirm lessened edema seen in sequential brain scans during earlier trials.
The Huntington's deal aims at furthering work done with FGF-2 by scientists at Buck, who have tested the protein in cell-based and animal models, gaining a 150 percent increase in new nerve cells. FGF-2 therapy extended the lifespan of the affected mice by 20 percent, and gave them better motor performance, decreased cell death and less of the amount of toxic aggregates that typically form in the brains of those affected by Huntington's.
But the potential nearer-term star in NTI's pipeline is Viprinex, a defibrinogenating thrombin-like enzyme for stroke derived from the venom of the Malayan pit viper, a reprofusion agent like Genentech Inc.'s Activase (tissue-plasminogen activator, or t-PA), but designed to be given up to six hours after a stroke instead of within three hours, as with t-PA. Phase III trials with Viprinex so far have failed in one instance and succeeded in the other. (See BioWorld Financial Watch, Feb. 5, 2007.)
A particularly challenging indication, stroke has defeated plenty of drugs already, such as Renovis Inc.'s Cerovive, also known as NXY-059, which failed in a Phase III trial and sent partner AstraZeneca plc packing. Nuvelo Inc.'s alfimeprase, partnered with Bayer HealthCare AG, failed two Phase III studies, one in acute peripheral arterial occlusion (PAO) and the other in catheter occlusion (CO). Intended to degrade fibrin when delivered through a catheter at the site of a blood clot, alfimeprase missed its primary endpoint in avoiding open vascular surgery within 30 days of treatment in the PAO setting, and failed to hit its primary endpoint of restoring function at 15 minutes in CO, relative to placebo. Neither trial met secondary endpoints, either.
Other companies made stroke-related news last week. Stem Cell Therapeutics Corp. reported getting a "no objection" letter from Health Canada for its REGENESIS trial, a Phase II prospective, randomized, double-blind, placebo controlled study of NTx-265, a human chorionic gonadotropin and epoetin alfa in acute ischemic patients. Stem Cell wants to fully enroll 120 patients before the end of next year.
In November, the German firm Paion AG said it would seek a new U.S. partner for the lead compound desmoteplase, which Paion plans to advance despite inconclusive results in June from a Phase III stroke trial that yielded a greater-than-expected response in the placebo group. Forest Laboratories Inc. returned rights to the product in August, and Paion has completed a reanalysis of the Phase III data, determined to move desmoteplase, a plasminogen activator derived from vampire bat saliva, into another study focusing on patients with obstructed major brain arteries.
NTI already markets Namenda (memantine), an N-methyl-D-aspartate antagonist for Alzheimer's disease - a compound with "limited upside potential," noted Dawson James analyst Stephen Dunn in a recent report. Dunn is bullish on NTI, however, pointing out that Viprinex trials have passed four reviews by the data safety monitoring board, and noting that the firm's recent financing provides a "solid cushion" for ongoing research. Near the end of October, NTI priced a public offering of 21.8 million shares at $2.75 per share, for gross proceeds of $60 million. Dunn has a "speculative buy" rating on NTI, with a 12-month to 18-month target price of $7.