First trial of new Humanized Engineering (TM) Mab.
OURCE: XOMA Ltd.
XOMA's Human Engineered ING-1 Cancer Antibody Shows Encouraging
Clinical Safety Profile and Low Immunogenicity in Patients
Clinical Data Reported at ASCO
BERKELEY, Calif.--(BW HealthWire)--May 20, 2002--Results of a Phase I clinical study of XOMA Ltd.'s
(Nasdaq:XOMA - News) Human Engineered(TM) ING-1(heMab) monoclonal antibody in patients with solid tumors
show safety and tolerability results that support further clinical development, according to research presented at the 38th
Annual Meeting of the American Society of Clinical Oncologists (ASCO) in Orlando, Florida. Additional data presented at
the meeting suggest that XOMA's patented Human Engineering(TM) methodology effectively yields therapeutic antibodies
with minimal immunogenicity in humans, comparable to antibody humanization methods.
"We were pleased to show not only that ING-1 was well tolerated by the cancer patients treated in this study, but also that
this Human Engineered(TM) antibody is similar in immunogenicity to monoclonal antibodies than have been modified by
other humanization methods," said Marc Better, PhD, vice president of technical development at XOMA. "The Human
Engineering(TM) technology was developed at XOMA, and further demonstrates our company's long-held expertise in the
field of monoclonal antibody engineering and development."
Safety and Tolerability of ING-1
The open-label, dose-escalating Phase I study was conducted at the University of Alabama Comprehensive Cancer Center
and the Cancer Therapy and Research Center in San Antonio, Texas. This study was designed to evaluate the safety,
tolerability, immunogenicity and pharmacokinetics of intravenously administered ING-1(heMab) in patients with advanced
adenocarcinomas of the breast, GI tract (colorectal, pancreatic, gastric, esophageal), lung, ovary, and prostate refractory to
standard therapies.
Twenty-two advanced adenocarcinoma patients received a median of two courses of ING-1(heMAb) as a one-hour
infusion at one of four dose levels: 0.03, 0.1, 0.3 or 1.0 mg/kg. Dose-limiting reversible events (amylase and lipase
elevations with abdominal pain) were seen at 1 mg/kg, precluding further dose escalation. Adverse events were mild at
doses of 0.3 mg/kg or less, and included rigors, chills and mild fever that responded well to antipyretics and antihistamines.
Although efficacy was not an endpoint, investigators reported no objective tumor responses in this short-term study, but
two patients had stable disease at three months. The maximum tolerated dose of ING-1 given intravenously every 21 days
was 0.3 mg/kg and, at that dose, the ING-1(heMAb) half-life was 30.6 +/- 3.4 hours (mean +/- S.E.), and at that dose, the
antibody reached plasma concentrations that have showed anti-tumor activity in preclinical models.
"The relatively brief half-life and good tolerability seen for ING-1 in this study have encouraged our further exploration of
this antibody at a weekly dosing schedule," said Dr. Better. "We have now completed enrollment in a second ING-1 study,
and expect to begin enrollment in an additional study soon, including an evaluation of subcutaneous administration."
ING-1 Immunogenicity
ING-1 is the first Human-Engineered(TM) antibody to be administered in human clinical studies. This patented
technology is an alternative to other methods used to minimize immunological reactions by human patients to antibodies of
rodent or other non-human origins. Such reactions can preclude repeated dosing with the same antibody, among other
problems. Ideally, modified antibodies are invisible to the human patient's immune system while retaining the binding
affinity and therapeutic activity of the non-human antibody.
To evaluate ING-1's immunogenicity in patients, the investigators evaluated blood samples from the 22 participants in the
Phase I clinical trial for antibody response to ING-1. Of 17 evaluable patients, only two had a detectable immune response
to ING-1, one patient after 2 doses, and another after 3 doses of 0.3 mg/kg. These data suggest that
Human-Engineered(TM) ING-1 is comparable in immunogenicity to humans to therapeutic antibodies humanized using
other methods.
About XOMA
XOMA develops and manufactures innovative biopharmaceuticals for disease targets that include cancer, immunological and inflammatory disorders, and
infectious diseases. XOMA's programs include collaborations with Genentech, Inc. on the Xanelim(TM) antibody for psoriasis (Phase III), rheumatoid
arthritis (Phase II) and other indications; with Onyx Pharmaceuticals, Inc. to develop and manufacture its Onyx-015 product for various cancers (Phase II
and III); with Baxter Healthcare Corporation to develop NEUPREX® (rBPI21) for Crohn's disease (Phase II) and other indications; and with Millennium
Pharmaceuticals, Inc. to develop two biotherapeutic agents, CAB2 and MLN01, for cardiovascular inflammation indications (preclinical). Earlier-stage
programs include developing compounds to treat cancer, retinopathies, autoimmune diseases and infections. For more information about XOMA's pipeline
and activities, please visit XOMA's web site at www.xoma.com.
Statements made in this news release related to product development or that otherwise relate to future periods, are forward-looking statements within the
meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. These statements are based on assumptions
that may not prove accurate. Actual results could differ materially from those anticipated due to certain risks inherent in the biotechnology industry and for
companies engaged in the development of new products in a regulated market. These risks, including those related to the timing or results of pending and
future clinical trials, changes in the status of existing collaborative relationships, the ability of collaborators and other partners to meet their obligations,
market demand for products, actions by the Food and Drug Administration or the U.S. Patent and Trademark Office and uncertainties regarding the status
of biotechnology patents, are discussed in XOMA's most recent annual report on Form 10-K and in other SEC filings. Consider such risks carefully in
evaluating XOMA's prospects. |
