Vion Pharmaceuticals, Inc. | Frequently Asked Questions

A: Onrigin™ (laromustine) Injection, formerly Cloretazine® (VNP40101M), is a novel cytotoxic agent that works by damaging DNA. Onrigin™ releases the DNA chloroethylating agent 90CE after entering the blood stream. 90CE is capable of chloroethylating the O6 position of guanine residues, ultimately resulting in an interstrand DNA cross-link. Interstrand DNA cross-links are difficult to be repaired and are toxic to cells. Onrigin™ demonstrated a broad spectrum of anticancer activity in preclinical studies, including activity in selected cell lines resistant to other alkylating agents such as BCNU, cyclophosphamide and melphalan. In preclinical studies, Onrigin™ has been combined with other anticancer agents such as cytarabine (Ara-C). In addition, Onrigin™ or its metabolite has been shown to be capable of crossing the blood brain barrier in preclinical models.

Q. What stage of development is Onrigin™ (laromustine) Injection in?

A: In February 2009, we filed a New Drug Application (NDA) for Onrigin™ with the U.S. Food and Drug Administration for remission induction treatment in elderly patients with de novo poor-risk AML. In September 2009 the Oncologic Drugs Advisory Committee (ODAC), which is the cancer drug advisory panel of the U.S. Food and Drug Administration (FDA), voted in favor of Vion completing a randomized study defining the efficacy and safety of the Company’s lead oncology therapeutic Onrigin™ (laromustine) Injection prior to receiving regulatory approval from the FDA. Vion had presented data for Onrigin™ for remission induction treatment for patients sixty years of age or older with de novo poor-risk acute myeloid leukemia (AML). In December 2009, we received a complete response letter from the FDA. The letter indicates that the FDA cannot approve the Company's NDA in its present form and provides recommendations to address the remaining issues. The complete response letter advised that the Company complete a randomized study or studies to define the efficacy and safety of Onrigin™ in the patient population proposed for the indication, and that the study or studies should be designed to demonstrate a survival benefit that is clearly attributable to Onrigin™ with an acceptable safety profile in a well-characterized patient population. In addition to clinical and statistical recommendations, the letter also addressed clinical pharmacology and manufacturing issues. The complete response letter also requested that the Company provide an update on Onrigin™ safety information when the issues above had been addressed.

Q. In what clinical trials is Onrigin™ (laromustine) Injection being evaluated?

A: Clinical trials of Onrigin™ are underway in: (i) AML and myelodysplastic syndrome (MDS) in combination with cytarabine; (ii) AML and MDS in combination with standard remission-induction therapy; (iii) AML with unfavorable cytogenetics in combination with standard remission-induction chemothrapy; and (iv) brain tumors in combination with temozolomide.

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Triapine®

Q. What is Triapine® and how does it work?

A: Triapine® is a small molecule that inhibits an enzyme, ribonucleotide reductase, necessary for the synthesis of DNA. Synthesis of DNA is necessary for cancer cells to replicate; therefore inhibition of the ribonucleotide reductase enzyme prevents cancer cells from dividing in the body. Disruption of DNA synthesis in some cancer cells will also cause their death.

DNA synthesis is also involved in repairing damage to cancer cells that have been treated with many of the standard cancer chemotherapy agents, which work by damaging DNA. The ability of cancer cells to rapidly repair DNA damage is one reason that cancer cells become resistant to standard chemotherapy agents. Because Triapine® inhibits DNA synthesis, it can inhibit DNA repair, and therefore it may be able to increase the antitumor effects of many of the common anticancer drugs. Experiments conducted by Vion and Yale scientists have shown that Triapine® can increase the antitumor effects of standard cancer agents such as cisplatin, cyclophosphamide, and etoposide in mouse tumor models.

Q. What is the status of Triapine® clinical trials?

A: Triapine® is being evaluated in clinical trials sponsored by the National Cancer Institute. Search "Triapine" at www.clinicaltrials.gov for a list of trials.

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