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Callisto Pharmaceuticals Reports Promising Interim Phase II Data for Atiprimod in Advanced Carcinoid Cancer

NEW YORK--(BUSINESS WIRE)--May 16, 2008 - Callisto Pharmaceuticals, Inc. (AMEX: KAL; FWB: CA4), a developer of new drug treatments in the fight against cancer and gastrointestinal disorders, announced today promising interim data from the company's ongoing open-label Phase II clinical trial of Atiprimod to treat low to intermediate grade neuroendocrine carcinoma (advanced carcinoid cancer). Overall, the interim results suggest that Atiprimod is an active and well tolerated drug in the treatment of carcinoid cancer.

In this interim analysis, 25 of 46 enrolled patients had sufficient data available for evaluation. The median follow up of the patients was 6 months (range 2 to over 12 months). All patients enrolled in this study had evidence of progressing disease in the 6 months preceding enrollment. Details of this analysis will be presented at the 44th annual meeting of the American Society of Clinical Oncology (ASCO), which will be held in Chicago May 30-June 3, 2008.

Interim analysis patient selection: The efficacy reporting includes all patients for which screening baseline data and at least Cycle 2 RECIST measurements were available, as well as patients who had progressive disease before Cycle 2 at the cut off time for the analysis. The safety reporting includes all reported SAE information as of the cut off date for all 46 enrolled patients.

Tumor response analysis: Of the evaluable patients, 92% had stable disease as best response per standard RECIST criteria, with a median duration of 6 months. Actuarial progression free survival at 6 months is 76% and at 12 months it is 50%. There were no objective RECIST responses for tumor regression in the analyzed cohort. To date, 7 patients have completed all 12 planned cycles of Atiprimod therapy with stable disease and have entered an extension trial to continue treatment.

Symptom relief analysis: In this analysis, 17 patients were evaluable for relief of symptoms of carcinoid cancer (flushing, wheezing, diarrhea). 82% of patients responded with at least 1 treatment cycle's daily average frequency of at least 1 symptom that was reduced by 20% or more from the screening daily average for that symptom, as recorded by the patients in a daily diary. The breakdown in responding symptoms were wheezing (2), flushing (11) and diarrhea (5). (The number of symptom responses exceeds the number of responding patients because some patients had more than one symptom response.) Some of these symptom responses were quite clinically striking and durable; for example, one patient had a steady reduction in daily flushing frequency from nearly 6 episodes per day to less than one episode per day by Cycle 7. This patient is continuing in his 8th treatment cycle.

Side effect analysis: Serious Adverse Events (SAE's) from all 46 patients enrolled in the study and reported to date have been analyzed. 15 SAEs were reported in 13 unique patients. Nine of the 15 SAEs were assessed as unrelated to Atiprimod by the treating investigator. Four SAEs were assessed as possibly related, 1 as probably, and 1 as definitely related. Of the 6 patients with SAEs assessed as possibly, probably, or definitely related, all involved up to grade 4 AST/ALT elevations with or without nausea and vomiting. Grade 1-2 bilirubin elevations were noted in 3 of these. All of the 6 patients with SAEs of abnormal liver function have recovered and 2 of these patients were able to subsequently continue Atiprimod. Detailed dose modification guidelines for liver function abnormalities are included in the protocol. Two SAEs had an outcome of death - both were assessed as unrelated to Atiprimod and involved complicated urinary tract infections in elderly patients. Of the 13 remaining SAEs occurring in 11 unique patients in whom the outcome of the SAE was not death, 6 patients discontinued study participation because of the SAE.

Study design: The study is an open label Phase II study designed to evaluate the anti-tumor efficacy, effect on symptoms, safety and tolerability of Atiprimod over 12 treatment cycles (about 12 months) in patients with low to intermediate grade neuroendocrine carcinoma (also called carcinoid cancer) who have metastatic or unresectable cancer. Patients in the study must have either progression of their cancer or symptoms from their carcinoid tumor which is not controlled with standard octreotide therapy. Forty-six patients were enrolled in the study, all of whom had progressing disease in the six months preceding enrollment. In addition, patients were required to complete two weeks of a symptoms diary to establish their symptoms baseline before commencing Atiprimod dosing. Atiprimod is given orally according to a pharmacokinetically-driven dosing regimen in 4-week cycles.

"We are pleased with the results that Atiprimod has shown so far in this trial," said Dr. Gary S. Jacob, Chief Executive Officer of Callisto. "Importantly, in this slow growing cancer, Atiprimod has shown an ability to stabilize disease progression and to reduce the symptoms of this disease, with a side effect profile that is generally well tolerated, with reversible increases in liver transaminases as the most notable adverse event. This appears to be a drug that patients can tolerate for long term treatment in this slowly progressing disease. We hope to be able to meet with the FDA, sometime in the next twelve months, to discuss the design of a pivotal Phase III trial."

Dr. Max Sung from the Mount Sinai School of Medicine in New York, the lead investigator on the study, stated: "In this interim analysis, Atiprimod has shown a clear trend towards stabilizing patients who previously had progressive disease. This is a very important finding and I believe that this drug has the potential to become a first line therapy for this cancer."

Said Dr. Jacob: "This is the start of realizing the potential of Atiprimod in various cancers. Carcinoid is an excellent initial indication for Atiprimod. Importantly, the end point in this trial, progression free survival, has been accepted by the FDA as the primary endpoint for other recent phase III trials in this disease. In addition to a phase III trial in carcinoid cancer, we will also start to investigate possible designs of exploratory phase 2 programs in other cancers where we believe the drug has potential, such as liver and colon cancer."

Atiprimod has been given orphan drug designation to treat carcinoid cancer.

About Carcinoid cancer

Carcinoid tumors, or carcinoids, originate in hormone-producing cells of the gastrointestinal (GI) tract, the respiratory tract, the hepatobiliary (liver) system and the reproductive glands. The most common site of origin is the GI tract, especially the small bowel. There are about 7,000 new cases of carcinoid cancer diagnosed annually, with the number increasing over the past 20-30 years. Carcinoid tumors that metastasize to the liver have a poor prognosis. Traditionally, chemotherapy relieves symptoms in less than 30% of cases of metastatic carcinoid tumors, usually for less than 1 year. Very few drugs that have been tested in this cancer have shown clinically meaningful efficacy. Carcinoid tumors often produce a condition called "carcinoid syndrome" which is caused by the release of hormones from the tumors into the blood stream. The symptoms vary depending on which hormones are released by the tumors, but typically include diarrhea, facial flushing, wheezing, abdominal pain and valvular heart disease.

About Callisto Pharmaceuticals, Inc.

Callisto is a biopharmaceutical company focused on the development of new drugs to treat various forms of gastrointestinal diseases and cancer. Callisto's drug candidates include two anti-cancer agents as well as a drug for gastrointestinal disorders that is currently being developed by its wholly-owned subsidiary, Synergy Pharmaceuticals. The Company's lead drug in the clinic, Atiprimod, is presently in a Phase II clinical trial in advanced carcinoid cancer, a neuroendocrine tumor, and in a Phase II extension trial in advanced carcinoid cancer patients. Callisto's second drug in the clinic, L-Annamycin, is currently in a Phase I/II clinical trial in adult relapsed or refractory acute lymphocytic leukemia, and in a Phase I clinical trial in children and young adults with refractory or relapsed acute lymphocytic leukemia or acute myelogenous leukemia. Synergy's proprietary drug SP-304 is planned to begin clinical development in 2Q2008 for gastro-intestinal disorders. SP-304 is a synthetic analog of the human gastrointestinal hormone uroguanylin, and acts by activating the guanylate cyclase C (GC-C) receptor on epithelial cells of the colon. Callisto is also listed on the Frankfurt Stock Exchange under the ticker symbol CA4. More information is available at

Forward-Looking Statements

Certain statements made in this press release are forward-looking. Such statements are indicated by words such as "expect," "should," "anticipate" and similar words indicating uncertainty in facts and figures. Although Callisto believes that the expectations reflected in such forward-looking statements are reasonable, it can give no assurance that such expectations reflected in such forward-looking statements will prove to be correct. As discussed in the Callisto Pharmaceuticals Annual Report on Form 10-K for the year ended December 31, 2007, and other periodic reports, as filed with the Securities and Exchange Commission, actual results could differ materially from those projected in the forward-looking statements as a result of the following factors, among others: uncertainties associated with product development, the risk that products that appeared promising in early clinical trials do not demonstrate efficacy in larger-scale clinical trials, the risk that Callisto will not obtain approval to market its products, the risks associated with dependence upon key personnel and the need for additional financing


Callisto Pharmaceuticals, Inc.
Gary Jacob, Ph.D., +1-212-297-0010
Russo Partners
Tony Russo, +1-212-845-4251
Web site:

Posted: May 2008