Agennix Inc. said its recombinant human lactoferrin product, talactoferrin, showed substantially improved response rates in patients with non-small-cell lung cancer when combined with first-line chemotherapy.

Results from the 110-patient Phase II trial, presented at the 96th annual meeting of the American Association for Cancer Research in Anaheim, Calif., also reported the drug was safe and well tolerated.

As the first company to produce commercial quantities of human lactoferrin for pharmaceutical purposes, Agennix has several ongoing Phase II trials in cancer and wound treatment for talactoferrin alfa, an immunostimulatory protein based on a multifunctional protein found in human milk and other endocrine secretions.

Talactoferrin is designed as an orally administered liquid that binds to specific receptors in the gastrointestinal tract, and stimulates the production of cytokines that activate immune cells such as CD-8+ and NK-T cells.

The goal of the Phase II combination study was to determine whether talactoferrin alfa improves the effectiveness when added to a standard chemotherapy regimen such as carboplatin/paclitaxel in chemotherapy-na ve patients with an advanced form of the disease. Patients were randomized to receive chemotherapy plus either talactoferrin or placebo in 35-day cycles for up to three cycles or until radiological progression. The primary endpoint relied on the measure of overall response by CT scans, using RECIST (Response Evaluation Criteria in Solid Tumors).

Agennix reported results confirming response rates in all 110 patients increased from 27 percent with placebo to 42 percent with talactoferrin, a relative increase of 56 percent. Of the 100 evaluable patients (meaning they had at least one CT scan after starting treatment) their response rates increased from 29 percent to 47 percent, a relative improvement of 62 percent.

The Houston-based company said the positive findings support further development of the product in NSCLC.

Results from the other Phase II trials of talactoferrin are expected within the next few months. In addition to NSCLC, the product is being evaluated in renal cancer and as a topical gel formulation in patients with diabetic foot ulcers.

The company announced last month that it had raised $22 million in a private placement to fund continued development of talactoferrin, including the Phase II trials and the initiation of a Phase III program. (See BioWorld Today, March 31, 2005.)

In other news from AACR:

• Adventrx Pharmaceuticals Inc., of San Diego, presented CoFactor toxicity and pharmacodynamics data collected from its ongoing CoFactor Phase II trial in metastatic colorectal cancer that suggested there is negligible risk of toxicity. The metabolism of intravenously administered CoFactor (CH2FH4) at 60 mg/m2, resulted in marked RBC folate pool expansion and showed no immediate or delayed formic acid excretion. Adventrx said the product might be associated with a decrease in urinary formate.

• American BioScience Inc., of Santa Monica, Calif., gave several presentations related to its nanoparticle albumin-bound (nab) technology platform, including the demonstration of improved efficacy and lower toxicity of Abraxane vs. Taxotere (Sanofi-Aventis Group) in preclinical xenograft tumor models. Another presentation demonstrated the significantly lower toxicity of nab-docetaxel vs. Taxotere in a preclinical model and a third presentation showed the development of nab-17AAG, the nanoparticle version of the heat-shock protein 90 inhibitor.

• Array BioPharma Inc., of Boulder, Colo., presented two posters showing the activity of its ARRY-334543, a small-molecule inhibitor designed as a reversible, nanomolar potent, enzymatic and cellular inhibitor of the key growth factor receptor tyrosine kinases, EGFR and ErbB-2. The company said the compound showed improved physiochemical properties relative to compounds in clinical development directed at the same targets, and also provided superior exposure and equivalent or greater efficacy in xenograft models of human cancer. ARRY-334543 is in regulated safety assessment.

• BioVex Ltd., of Oxford, UK, presented details of its recent Phase I/II trial of OncoVEX, an oncolytic virus designed to selectively kill tumor cells while also inducing tumor cells to secrete GM-CSF, an immune stimulator to enhance the destruction of metastatic tumor deposits. Results from the administration of OncoVEX in either single or multiple doses have shown the product to be well tolerated, and substantial biological effects, including tumor necrosis, have been observed.

• CancerVax Corp., of Carlsbad, Calif., said its subsidiary, Cell Matrix Inc., presented preclinical data on a new approach in anti-angiogenesis therapy that selectively targets sites of tumor neovascularization. The data demonstrated that CancerVax's humanized anti-denatured collagen antibodies significantly inhibited tumor cell growth in a dose-dependent manner in several in vivo tumor models compared to controls. The company expects to submit an investigational new drug application in the first quarter of 2006 for D93 to treat solid tumors.

• Ciphergen Biosystems Inc., of Fremont, Calif., said studies of its SELDI ProteinChip technology for biomarker discovery, including a study using the CiphergenExpress and Biomarker Patterns Software, demonstrated good sensitivity and specificity in distinguishing a breast cancer population from patients with benign breast lesions from healthy controls.

• EntreMed Inc., of Rockville, Md., presented preclinical data for its Proteinase Activated Receptor (PAR-2) Inhibitor program indicating that PAR-2 antagonists inhibit tumor growth and the formation of new blood vessels in animal models. The antagonists of PAR-2 signaling also demonstrated a potential relationship between the onset of inflammation and the regulation of tumor growth and angiogenesis. PAR-2 is a cell-surface receptor that is known to play a critical role in mediating acute and chronic inflammation, and EntreMed said it has developed multiple peptides and small molecules designed to block that receptor's activity, including the PAR-2 antagonists.

• Genta Inc., of Berkeley Heights, N.J., said preclinical data have shown that Genasense (oblimersen sodium injection) might enhance the antitumor activity of Iressa (gefitinib, AstraZeneca plc) in non-small-cell lung cancer. Results of experimental xenograft models indicated that Genasense used alone showed somewhat greater inhibition of tumor growth in mice compared with single-agent gefitinib. However, the combination of both drugs yielded considerably enhanced antitumor activity, and researchers said it appeared the addition of Genasense might overcome naturally occurring resistance to gefitinib. Further preclinical studies evaluating Genasense in combination with Tarceva (erlotinib, OSI Pharmaceuticals Inc.) and Alimta (permetrexed, Eli Lilly and Co.) have revealed similar results.

• Oncolytics Biotech Inc., of Calgary, Alberta, expects to present a poster today supporting the use of a reovirus as a targeted therapy for melanomas. The research also showed that activation of certain classes of immune cells by the reovirus might enable additional antitumor activity beyond that of tumor cell death caused directly by the reovirus.

• OSI Pharmaceuticals Inc., of Melville, N.Y., presented a variety of data, including preclinical findings that showed cell lines and tumor xenografts that express epithelial markers might be more sensitive to Tarceva than those that express mesenchymal markers. Another study highlighted the use of RNA interference in the identification and validation of new drug targets suitable for exploration in combination with Tarceva. A final presentation showed that OSI-930, a co-inhibitor of the receptor tyrosine kinases c-kit and VEGFR, is equally active against both the mutant and wild-type versions of c-kit.

• OxiGene Inc., of Waltham, Mass., presented preclinical data for Combretastatin-A-4-P and OXi4503 that support development of the two products. One study showed that OXi4503 had single-agent activity against implanted SW1222 colon tumors and liver metastases in mice. Another study showed that CA4P-induced hypertension can be controlled with conventional anti-hypertensive agents, without compromising the reduction in tumor blood flow.

• Peregrine Pharmaceuticals Inc., of Tustin, Calif., presented data showing that the vascular targeting agent, VEGF121/rGel can inhibit tumor growth and bone metastases in mouse models of metastatic prostate cancer. Researchers reported that VEGF121/rGel inhibited tumor growth and enhanced the survival of mice by targeting the tumor vasculature, as well as by normalizing the number of mature osteoclasts found in bone. In the study, 50 percent of the drug-treated mice survived past day 140 without any sign of skeletal tumor lesions, while all the untreated mice developed significant metastatic lesions by the 67th day.

• Procyon Biopharma Inc., of Montreal, said research on PCK3145, a peptide in development for advanced metastatic prostate cancer, revealed that the product binds to the cell-surface laminin receptor and triggers a signaling cascade of events resulting in down-regulation of MMP-9 (matrix metalloproteinase 9), an enzyme involved in the breakdown of the extracellular matrix that allows tumors to spread. The company said those observations showed PCK3145's signal transduction inhibition effect and further corroborate its hit-and-run mode of action to support a once-weekly administration in the upcoming Phase IIb trial.

• Quintessence Biosciences Inc., of Madison, Wis., said it has begun preclinical studies on its Evade Ribonuclease lead candidate, QBI-139, described as a slightly modified version of a human protein. The ribonuclease after which QBI-139 is modeled is produced by the human pancreas and used in the digestion of food.

• Semafore Pharmaceuticals Inc., of Indianapolis, presented new in vivo data demonstrating the potential use of SF1126, the company's P13K inhibitor, delivered as a tumor-targeting prodrug. Semafore reported that the P13 pathway is a critical intercept point in cell signaling that controls multiple cellular functions, including angiogenesis, apoptosis, migration, invasion and metastasis.

• ZioPharm Inc., of New Haven, Conn., presented preclinical pharmacology and toxicology data for ZIO-201 (lysine-isophosphoramide mustard) demonstrating its activity in cyclophosphamide- and ifosfamide-resistant cancers. Data also showed that, because the product is directly active, there are no metabolites to cause the typical toxicities of cyclophosphamide or ifosfamide. ZIO-201 is ZioPharm's small-molecule alkylating drug in Phase I studies in patients with late-stage cancers.

• Spectrum Pharmaceuticals Inc., of Irvine, Calif., said data were presented on its synthetic prodrug Eoquin, updating results of a study performed in 12 patients with multifocal, low-grade, superficial cancer of the urinary bladder, who had received prior therapy and had recurrence of cancer. In eight out of 12 patients treated either with the recommended dose or with increasing concentrations of Eoquin, the marker tumor disappeared completely with no evidence of cancer. Two patients have been without recurrence of disease for 24 months.

• Telik Inc., of Palo Alto, Calif., said preclinical data show that Telcyta was not cross-resistant with carboplatin in carboplatin-resistant ovarian cancer cells and that the combination of Telcyta and carboplatin showed synergistic inhibition. Another study showed the synergistic inhibitory effects of both doublet and triplet combinations of Telcyta with platinum and taxane drugs as compared to the individual agents in human ovarian and non-small-cell lung cancer cells. Telik also presented data that provided details on the Telcyta-induced effects on cell-cycle progression and apoptosis.