SCLC trial results are Good so far!!

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Gemin X Announces Positive Results in Small Cell Lung Cancer from Phase 1b Trial of Obatoclax at Annual Meeting of the American Society of Clinical Oncology

100% Objective Response Rate in First Line Patients Supports Optimal Dose in Ongoing Phase 2 Portion of Study

MALVERN, Pa. & MONTREAL--(BUSINESS WIRE)--Gemin X Pharmaceuticals, a clinical stage biopharmaceutical company developing novel, targeted cancer therapeutics, today presented positive results from a Phase 1b clinical trial of its lead product candidate obatoclax (GX15-070) for the treatment of first line patients with extensive-stage small cell lung cancer (SCLC). Data from this study, which included 12 previously untreated patients, support that the three-hour infusion schedule of obatoclax can meaningfully enhance the effects of standard chemotherapy in SCLC patients. After six cycles of therapy, and based on RECIST measures, researchers observed a significant response rate among patients dosed with the obatoclax-chemotherapy combination – a confirmed Objective Response, defined as either a Partial Response or a Complete Response, was seen in 100% of patients, including two patients with Complete Responses. Importantly, no patients progressed during the planned six cycles of combination chemotherapy with obatoclax, and early trends suggest that duration of response will be similarly enhanced. These data were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Orlando, Florida.

Obatoclax is a small-molecule inhibitor of the Bcl-2 family of proteins, including the key protein Mcl-1. This Phase 1b dose-escalation study is instrumental in establishing safety and identifying an optimal dose for obatoclax, when administered in combination with standard doses of the chemotherapy agents carboplatin and etoposide, as both front-line and second-line therapy. After their planned six cycles of chemotherapy, patients achieving a response are eligible to receive single agent obatoclax as maintenance therapy - this portion of the clinical trial is ongoing.

“We are very pleased to be presenting this Phase 1b data at ASCO, as they reinforce the safety of obatoclax and directly support the design of our ongoing Phase 2 study of obatoclax in patients receiving first line therapy for extensive stage, small cell lung cancer. We view this unique Bcl-2 inhibitor – an antagonist of all of the relevant Bcl-2 prosurvival proteins – as having important and broad applicability in cancer treatment,” said Jean Viallet, M.D., Chief Medical Officer at Gemin X. “We are very encouraged by the 100% response rate seen in these previously untreated SCLC patients who enrolled in this Phase 1b trial. It is our hope that obatoclax’s differentiated mechanism will lead to substantial improvements in response to treatment, tolerability and survival for these patients.”

The Phase 1b study (total patients = 25) was designed to assess safety and select a dose from two dose schedules of obatoclax in combination with carboplatin and etoposide for a randomized Phase 2 clinical trial. The two schedules of obatoclax assessed in this trial were a three-hour and 24-hour infusion schedule. The objective response rate seen in previously untreated patients with the 24-hour infusion (n=6) was 66%. Previously treated patients (n=7) in the trial demonstrated a response rate of 43%.

This Phase 1b study was conducted as the first portion of an ongoing multi-center, randomized, open-label Phase 2 study that was initiated in March 2009. In this Phase 2 trial the clinical effect of a combination of carboplatin, etoposide and obatoclax (the “CEO” regimen) is being compared to the standard chemotherapeutic therapy alone (carboplatin and etoposide - the control arm) in patients with SCLC. The primary endpoint of the Phase 2 portion of the study, expected to enroll approximately 150 patients with SCLC, is comparison of overall response rate (ORR) for the obatoclax-containing arm versus the control arm. Secondary endpoints include comparison of progression free survival (PFS) and overall survival (OS), as well as safety. Enrollment for the trial is expected to be completed by the end of the third quarter of this year.

About Obatoclax

Obatoclax, Gemin X’s potential first-in-class small molecule antagonist of Bcl-2, is specifically designed to inhibit all relevant members of the Bcl-2 family of proteins, including the dominant member, Mcl-1. Inhibition of Mcl-1 and other Bcl-2 related proteins enhances cancer cell death by facilitating apoptosis and/or autophagy. These proteins have been shown to have a pro-survival effect in malignant cells; thus their inhibition by obatoclax could increase the activity of the drug’s tumor killing effect. Obatoclax has been shown to activate cancer cell death in vitro, to exhibit anti-tumor activity in animal models, and to enhance the effects of chemotherapy in various models including with the drugs carboplatin and etoposide. It has also shown single-agent biological and clinical activity in Phase 1 studies in a variety of cancer indications. Further, obatoclax has demonstrated an early ability to mechanistically evade the resistance built up by cancer cells to traditional chemotherapeutic agents.

Gemin X’s global development plan for obatoclax is focused on diseases marked by up-regulation of Mcl-1, including small cell lung cancer (in combination with carboplatin and etoposide), refractory acute lymphoblastic leukemia (in combination with dexamethosone) and systemic mastocytosis (as a single agent).

Small Cell Lung Cancer

Small cell is an aggressive form of lung cancer, and accounts for about 15% of all lung cancer cases, according to the American Cancer Society. Chemotherapy alone or combined with radiation is the usual treatment of choice for small cell lung cancer. According to the Journal of Clinical Oncology, the median survival time is approximately nine to 12 months with currently available therapies and the five-year survival rate for patients with extensive stage SCLC is less than 1%. Improved diagnostic and surgical techniques and novel combination therapies that can further extend patient survival are desperately needed to positively impact these outcomes.

About Gemin X Pharmaceuticals

Gemin X is developing first-in-class cancer therapeutics based on reinitiating programmed cell death, or apoptosis, inducing cancer cell self-digestion, or autophagy, and the inhibition of metabolism in cancerous cells. Gemin X currently has several clinical development programs underway, including Phase 2 clinical trials for its lead product candidates obatoclax (GX15-070), an innovative pan Bcl-2 inhibitor, and GMX1777, a novel inhibitor of NAD+ synthesis, and preclinical studies for its Telomere Capping and SMAC Mimetic programs. Potential treatment indications for the full scope of pipeline programs span a broad range of hematological and solid tumors, including chronic lymphocytic leukemia (CLL), melanoma, small cell lung cancer (SCLC), refractory acute lymphoblastic leukemia (ALL) and systemic mastocytosis. Founded in 1998, Gemin X is privately held with drug development and executive headquarters in Malvern, Pennsylvania and drug discovery operations in Montréal, Canada. For more information, please visit www.geminx.com.

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