By Frances Bishopp
Ilex Oncology Inc. and MPI Development Inc. have formed a limited partnership for the development of piritrexim, a DNA synthesis inhibitor being developed for the treatment of bladder cancer, early stage Kaposi's sarcoma (KS) and other cancers.
Ilex and MPI will jointly own, finance and manage the new venture and share equally in the future of piritrexim, Beth Shapiro, marketing communications manager at Ilex, told BioWorld Today.
Ilex will receive an up-front licensing fee, milestone payments and royalties from the joint venture, the financial details of which have not been disclosed. In addition, MPI has made a $5 million equity investment in Ilex.
Jerry Mitchell, CEO of MPI Development, will join the board of directors of Ilex, Shapiro said, and Ilex, of San Antonio, will have an opportunity to review any new technologies in the field of oncology discovered or acquired by MPI.
MPI Development and MPI Research are affiliated drug evaluation and development companies located in Mattawan, Mich. MPI Research is a full-service contract toxicology and phamacokinetics research laboratory. MPI Development provides medical expertise, biostatistical and data management technology, and extensive clinical development experience for guiding drugs through the regulatory process under contracts or equity partnerships with pharmaceutical and biotechnology companies in the U.S., Japan and Europe.
Piritrexim is a dihydrofolate reductase inhibitor that rapidly enters tumor cells by passive diffusion and inhibits DNA synthesis. It is a member of the antifolate group of cytotoxic agents whose known mechanism of action depends on interference with the synthesis of pyrimidine and purine nucleotides and DNA. Piritrexim also has potent antiprotozoal activity against Pneumocystis carinii and Toxoplasma gondii.
Piritrexin currently is in a double-blind, placebo-controlled Phase III clinical study to determine time to progression of disease in patients with early-stage, AIDS-related Kaposi's sarcoma and two Phase II pivotal studies in patients with advanced bladder cancer, who have failed front-line therapy, Shapiro said.
In two randomized, placebo-controlled Phase II clinical trials in patients with newly diagnosed, stage 1 (good risk) AIDS-related Kaposi's sarcoma, piritrexim was highly effective in reducing the rate of appearance of new KS lesions, Shapiro said. In the same studies, there was a suggestion that there were fewer opportunistic infections in the piritrexim-treated patients than in the placebo-treated patients, she said.
Additional studies suggest that KS patients who have failed or progressed on anthracyclines respond to piritrexim.
A Phase II study of piritrexim administered a low-dose regimen (25 mb/TID) daily for five consecutive days, repeated weekly for three weeks, followed by one week of rest. Dose modification during second and subsequent courses was based on the degree of toxicity observed. Enrolled patients were all males (26-50 years) and the median time from diagnosis of KS to enrollment was four months.
Piritrexim was reasonably well tolerated: 30 percent experienced neutropenia, 15 percent, anemia, 10 percent , thrombocytopenia and 7 percent, nausea. No cases of rash, mucositis, vomiting or alopecia were reported.
Eight of the patients treated were in stage 1, five in stage II and one in stage III of AIDS-related KS. Thirteen patients were evaluable and five patients responded to treatment, all of whom were stage 1 patients, providing a response rate greater than 50 percent for stage 1 patients.
Ilex currently has a number of cancer drugs in clinical development and has filed a new drug application for Mitoguazone for refractory or relapsed AIDS-related non-Hodgkin's lymphoma.
Another product, Crisnatol, has demonstrated significant clinical activity against recurrent glioblastomas and has been generally well tolerated.
In addition to its potential use in prostate cancer, Ilex has secured an orphan drug designation for DHAC in the treatment of mesothelioma and has applied for patent protection for the use of DHAC in combination with certain hormonal treatments.
Ilex, a privately held company, was formed three years ago as a spin-off of The Cancer Therapy and Research Foundation of South Texas, a non-profit treatment and drug testing center, which owns 30 percent of the company.
As of Dec. 12, 1996, Ilex had $23.4 million in cash on hand. The company's burn rate is approximately $200,000 a month. In December of 1996, Ilex registered to sell 2.5 million shares of stock between $11 and $13 a share. (See BioWorld Today, Dec. 23, 1996, p. 1.) *