Structural GenomiX Inc. brought onboard a clinical-stage cancer drug, bolstering its early stage oncology pipeline.

The San Diego-based company acquired worldwide rights from Shire BioChem Inc. to Troxatyl, a product in Phase I/II trials for acute myelogenous leukemia (AML). It's the first clinical candidate for SGX, which plans to complete the ongoing studies and advance Troxatyl into a Phase II proof-of-principle program early next year.

"It's a very important step in our strategic plan to accelerate the development of our oncology pipeline," Stephen Burley, the company's chief scientific officer, told BioWorld Today. "And we've got a good team to take Troxatyl forward."

In exchange for rights to the drug, SGX will make an up-front payment to Laval, Quebec-based Shire, a unit of Shire Pharmaceuticals Group plc, and would pay milestone payments based on successful development and approval of Troxatyl. It also would pay royalties on net sales. Burley noted that SGX remains sufficiently capitalized to support terms of the deal and proceed with further development plans.

The company was drawn to the drug, which represents a new class of cancer drugs, for a couple of reasons. SGX said it is not subject to common de-activating mechanisms that can cause resistance to existing therapies, and its potential in multiple cancers is appealing. Preclinical studies have demonstrated activity against both solid tumors and hematological malignancies.

But AML remains Troxatyl's lead indication, as positive early clinical results were observed in a study of the drug delivered by intravenous bolus in that indication.

"Results from the AML trial thus far show promising anti-leukemic activity at doses that are well tolerated by the patients," Burley said. "We need to complete the dose-escalation study so that we can choose the Phase II dose."

Clinical studies to date in about 700 patients have tested the drug delivered by bolus intravenously, though SGX said recent studies have shown that Troxatyl is more effective when intravenously administered as a continuous infusion over four or five days. An ongoing continuous infusion study of AML patients who have failed two or more chemotherapy regimens, and, in some cases, bone marrow transplantations, has shown that continuous infusion can result in improved response rates, compared to intravenous bolus administration.

Burley noted that those findings mirror results obtained from preclinical studies using a similar delivery strategy. To that end, the eventual Phase II trial would make use of administration by continuous infusion.

Other studies have pointed to Troxatyl's potential in other hematological cancers, including blast-phase chronic myelogenous leukemia and myeloid dysplastic syndrome, as well as in various solid tumors. A Phase I/II study in solid tumors is in progress.

"Troxatyl is a non-natural nucleoside analogue," Burley said, "that acts as a DNA-chain terminator during DNA replication in rapidly dividing cells."

He added that advantages inherent in the drug's mechanism include its avoidance of drug metabolism and resistance associated with natural nucleoside analogues.

"Our goal, at present, is to take the drug all the way [through development]," Burley said. "Of course, that doesn't rule out the opportunity of partnering later on."

Beyond Troxatyl, products already in SGX's oncology pipeline stem from the application of its fragment-based lead discovery technology, FAST (Fragments of Active Structures). It relies on libraries of synthetically enabled fragments developed by SGX for hit-to-lead optimization, and later employs high-throughput co-crystallography, computational scoring and automated parallel synthesis.

The company's preclinical pipeline includes programs in leukemias, urological cancers and other solid tumors.

In one area of focus, SGX is studying Gleevec-resistant chronic myelogenous leukemia by targeting wild-type and Gleevec-resistant Bcr-Abl with compounds that hit both forms of the enzyme. (Gleevec is marketed by Novartis AG.) The program is in pharmacokinetic animal studies, and Burley said the company expects to establish in vivo efficacy by next year, followed by an investigational new drug application. Another area of focus is kinase targets for urological cancers. SGX is conducting the bladder and prostate cancer research in collaboration with UroGene SA, of Evry, France.

The FAST technology has produced programs in other disease areas as well, which are partnered.