BioNumerik Reports Preclinical Antitumor Data On Two Novel Supercomputer Engineered Anticancer Agents At 89th Annual AACR Conference

March 30, 1998

- Novel class of highly lipophilic camptothecins, known as Karenitecins, demonstrates potent oral antitumor activity, acceptable safety and appear to be insensitive to common tumor-associated drug resistance mechanisms

- BioNumerik's novel chemoprotecting agent BNP7787 appears to completely protect against major toxicities associated with widely used platinum anticancer drugs such as cisplatinum

New Orleans, LA - March 30, 1998 -- BioNumerik Pharmaceuticals, Inc. this week presented new research results on two novel supercomputer-engineered small molecule agents designed to help address significant existing problems in current cancer therapy. These results continue to strengthen the correlation between actual experimental observations and the computational simulations provided by BioNumerik's innovative supercomputer simulations and mechanism based approach to new pharmaceutical discovery and development.

Regarding BioNumerik's BNP7787 and Karenitecins, Martin D. Abeloff, M.D., Director of the Johns Hopkins Oncology Center, stated, "These drugs have the potential to make a significant impact on current cancer therapy. The data reported by BioNumerik is particularly meaningful because the discovery and design of both of these agents was supported by BioNumerik's mechanism based computational studies and supercomputer simulations."

Frederick H. Hausheer, M.D., BioNumerik's Chairman and Chief Executive Officer, presented these findings at the 89th Annual Meeting of the American Association for Cancer Research held March 28 - April 1, 1998.

In a presentation titled "Karenitecins: A Novel Class of Orally Active Highly Lipophilic Topoisomerase I Inhibitors", the results presented by BioNumerik of studies conducted in BALB/c mice indicate that orally administered Karenitecin had excellent antitumor activity against solid tumors (prostate, colon, breast, lung) and had superior antitumor potency compared to existing camptothecin derivatives. These results also demonstrate the ability of BioNumerik's Karenitecins to bypass common drug resistance mechanisms (MDR, MRP & LRP) to which many other camptothecins appear to be susceptible. Because its compounds are lipophilic, BioNumerik believes its Karenitecins will have enhanced tissue penetration, drug delivery and bioavailability compared to water soluble camptothecins.

Camptothecins, described as Topoisomerase I inhibitors, represent some of the most active anticancer drugs in existence. Due to formulation problems, however, the great majority of camptothecins in development or on the market have been made water soluble to allow easier drug dissolution and administration. BioNumerik believes that this approach may limit the utility of these drugs and the Company has developed a new generation of proprietary highly lipophilic (fat loving) camptothecins, known as Karentitecins, that have been designed to overcome problems that exist with camptothecin and the current camptothecin derivatives.

Using its mechanism-based approach, BioNumerik used its Cray supercomputers to construct a detailed computational model involving human Topoisomerase I and DNA in order to understand and more precisely target the key interactions between camptothecin-Topo I/DNA. BioNumerik used this information to guide and complement the discovery and optimization of novel compounds for laboratory synthesis and preclinical testing.

In a presentation titled "BNP7787: Administration In Vivo Results in Increased Therapeutic Index and Toxicity Reduction of Platinum Drugs", BioNumerik also presented data on its proprietary agent BNP7787, a novel water soluble disulfide that was engineered to increase the therapeutic index of cisplatin and carboplatin, two widely used anticancer drugs.

Although platinum chemotherapy is widespread, formulations of cisplatin and carboplatin have a major risk of kidney toxicity (cisplatin), nausea and vomiting, bone marrow suppression, neurotoxicity and other toxicities. BioNumerik has designed BNP7787 to enhance selective inactivation of toxic platinum drug species and to produce a less toxic drug relative to other protecting agents.

BioNumerik presented preclinical animal study data showing that BNP7787 can completely protect against cisplatin-induced renal, emesis and bone marrow toxicities and can increase cisplatin's antitumor activity. It also showed, for example, complete tumor remissions increased from 13% (with a 50% mortality rate due to cisplatin toxicity) in cisplatin only treated subjects to a 63% complete remission rate with no mortality or toxicity in subjects pretreated with BNP7787 prior to the same toxic dose of cisplatin. In addition to demonstrating safety and efficacy in preclinical studies, BioNumerik also confirmed that a single dose of BNP7787 could reduce the number of episodes and duration of vomiting by 75% and 89%, respectively, in a model of cisplatin induced vomiting. Preclinical studies have also shown that a single dose of BNP7787 substantially protects against cisplatin induced suppression of the bone marrow. It also showed BNP7787 is less toxic than table salt, making it non-toxic by pharmaceutical industry standards.

In presenting the data, Dr. Hausheer stated: "These preclinical studies demonstrate that BNP7787 appears to substantially protect against the common major toxicities of platinum chemotherapy and does not interfere with the antitumor activity of cisplatin. There appears to be reproducible evidence of potentiation or enhancement of cisplatin's antitumor effect by BNP7787. We have found that BNP7787 can safely and effectively protect against up to a 500% increase in the dosage of cisplatin, a 100 percent lethal dose under normal circumstances. To our knowledge, no drug has ever been reported to achieve this level of protection at such a high dose of cisplatin."

Dr. Hausheer added, "We have also obtained confirmatory preclinical data indicating that BNP7787 can protect against carboplatin associated toxicity. If we are able to safely administer higher and more effective doses of cisplatin and carboplatin to cancer patients, this may lead to improved patient response rates."

BNP7787 is currently in Phase I clinical trials in the United States at the University of Chicago Medical Center and the Roswell Park Cancer Institute and in Europe at the Free University Hospital in the Netherlands. Patient enrollment in Phase I is also scheduled to commence soon at The Johns Hopkins Oncology Center.

Richard L. Schilsky, M.D., Director of the University of Chicago Cancer Research Center and Principal Investigator for the University of Chicago BNP7787 Phase I trial indicated, "We are extremely pleased to have the opportunity to conduct Phase I trials on this exciting new drug. BNP7787 has great potential to make cisplatin and carboplatin safer and to provide meaningful increases in tumor response rates."

BioNumerik Pharmaceuticals, headquartered in San Antonio, Texas, is an emerging pharmaceutical company with an innovative, proprietary technology platform for the rapid discovery and clinical development of small molecule based pharmaceuticals for cancer. BioNumerik is a leader in a powerful new area called "mechanism based drug discovery" which integrates medicine, quantum physics, synthetic chemistry, pharmaceutical sciences and Cray supercomputing. BioNumerik views its approach as a fourth generation technology relative to drug screening, automated screening and combinatorial chemistry, and rational drug design. BioNumerik believes its approach has the potential to greatly reduce the time to discover and bring new drugs into clinical development and to reduce the risk of failure in clinical development. In less than 6 years, the Company has rapidly advanced two compounds into human clinical trials and a third new compound into late preclinical development.

***

Editor's Note: This release is also available on the Internet at: http://www.noonanrusso.com
-end-


Noonan/Russo Communications

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.