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Cortice Biosciences Announces Updated Results From Clinical Trials Evaluating TPI 287 for Treatment of Brain Malignancies

– 60% overall response rate; 12.9 month median and 71% 12-month overall survival in combination with Avastin® for treatment of recurrent glioblastoma –

– Complete response and stable disease observed with radiation for treatment of breast and lung cancer metastases to the brain –

– Safety profile remains favorable; no dose-limiting toxicities to date –

SAN ANTONIO, Nov. 20, 2015 (GLOBE NEWSWIRE) -- Cortice Biosciences announced today results from three clinical trials supporting the utility of TPI 287 for treatment of brain cancers. Outcomes to date from a Phase 1/2 trial evaluating TPI 287 plus bevacizumab (Avastin®) in patients with recurrent glioblastoma (GBM) previously untreated with bevacizumab continue to compare favorably to outcomes seen with bevacizumab alone in other studies. In addition, an early read of a Phase 1 trial provides the feasibility of combining TPI 287 with radiation for treatment of cancers metastatic to the brain. Presentations will be made this evening during a poster session at the 20th Annual Meeting and Education Day of the Society for Neuro-Oncology in San Antonio, TX.

TPI 287 is a novel microtubule stabilizing agent that readily penetrates the blood-brain barrier. Prior preclinical and clinical results support the potential of this agent for the treatment of aggressive brain cancers with few therapeutic options.

“With the addition of new study participants and longer follow-up, results from our TPI 287 development program for GBM remain impressive,” said George Farmer, Ph.D., Chief Executive Officer of Cortice. “Moreover, TPI 287 may have utility beyond GBM for treating the hundreds of thousands of patients who develop brain metastases from other tumor types each year, based upon an early positive trend in an on-going Phase 1 study. We look forward to presenting further updates from these trials in the near future.”

Results in detail

Cortice is running two multi-center Phase 1/2 clinical trials with TPI 287 in combination with bevacizumab for the treatment of patients with recurrent GBM who have not received prior bevacizumab (Study CB-017) or who have progressed through a bevacizumab-containing regimen (Study CB-018). The goal of both trials is to determine the maximum tolerated dose (MTD) of TPI 287 in combination with bevacizumab as well as objective response, progression free survival, and overall survival.

Recurrent Glioblastoma

CB-017: TPI 287 plus bevacizumab for treatment of recurrent GBM naïve to prior anti-angiogenic therapy

Twenty-four patients with recurrent GBM that has progressed beyond first-line treatment have been enrolled to date, of which 20 and 23 are evaluable for overall response and overall survival, respectively. In addition to TPI 287 (140 to 220 mg/m2 administered every three weeks in seven dose cohorts), all patients received standard-of-care bevacizumab (10 mg/kg every two weeks).

Key efficacy results are as follows:

  • Overall response
    • 12 patients achieved an objective response per RANO criteria (3 complete; 9 partial), corresponding to a 60% overall response rate
    • 8 patients achieved stable disease and 1 patient had progressive disease at first assessment for response, corresponding to a 96% disease control rate
  • Survival
    • Median progression free survival is 5.5 months [95% C.I. 4.1-6.9] after a median follow-up of 13.6 months
    • Median overall survival to date is 12.9 months [95% C.I. 10.9 – 18.2] after occurrence of 48% of possible events and a median follow up 13.6 months
    • Of 14 patients with sufficient follow-up, 10 (71%) were or have been alive for at least 12 months

CB-018: TPI 287 plus bevacizumab for treatment of recurrent GBM progressing after prior bevacizumab treatment

Seventeen recurrent GBM patients have been enrolled to date, all of which are evaluable for overall survival and 11 of which were evaluable for overall response. By virtue of having progressed on a prior bevacizumab-containing regimen, patients in CB-018 had more advanced disease than those enrolled in CB-017. All received the same regimen as in CB-017 at TPI 287 doses of 140 to 180 mg/m2 in 4 dose cohorts.

Key efficacy results are as follows:

  • Overall response
    • 1 patient achieved a complete response (on-going > 6.9 months) and 3 patients achieved stable disease per RANO criteria
  • Survival
    • Median progression free survival is 1.4 months
    • Median overall survival is 4.7 months [95% C.I 2.7-10.6]
    • Of 14 patients with sufficient follow-up, 5 (36%) were or have been alive for at least 6 months

Safety data available from 32 patients treated in both studies continues to demonstrate the favorable tolerability profile of this agent. With the exception of Grade 3 myelosuppression (3 patients), all adverse events regarded as possibly related to TPI 287 have been mild-to-moderate. No dose limiting toxicities (DLTs) have been observed to date.

“These results continue to support the potential of TPI 287 for treatment of glioblastoma,” said Dr. Samuel Goldlust, Medical Director of the Brain and Spine Institute of the John Theurer Cancer Center in Hackensack, NJ and Principal Investigator of these studies. “Still below the MTD for TPI 287, patient outcomes compare quite favorably to those seen with Avastin alone in previous landmark clinical trials.”

Secondary brain metastases

TPI 287 plus radiation for treatment of breast and non-small cell lung cancer metastases to the brain

Dr. Solmaz Sahebjam of the Moffitt Cancer Center in Tampa, FL will present preliminary results from a TPI 287 dose-escalation trial in combination with fractionated stereotactic radiotherapy (FSRT). Patients with up to three brain metastases are treated with 5 fractions of standard-of-care FSRT over one day and TPI 287 infused weekly for 3 weeks.

To date, 7 patients with breast or non-small cell lung cancer brain metastases have been treated. At the time of presentation, 3 patients were evaluable for intracranial response and 5 patients were evaluable for safety:

  • 14 mg/m2 cohort: Two patients with non-small cell lung cancer experienced stable disease
  • 28 mg/m2 cohort: One patient with ER/PR/HER2 positive breast cancer has a complete response that remains on-going for greater than 4 months
  • Treatment was well-tolerated with no Grade 3 or 4 adverse events observed

About TPI 287

TPI 287 is a novel taxoid which binds to and stabilizes the assembly of microtubules similarly to commonly used taxanes, including paclitaxel (Taxol® and Abraxane®) and docetaxel (Taxotere®). In oncology treatment settings, microtubule stabilization by these agents leads to mitotic arrest and cancer cell death. TPI 287 has advantages over these taxanes due to its ability to circumvent common drug resistance mechanisms and its propensity to penetrate the central nervous system. Accordingly, TPI 287 has the potential to treat primary brain tumors and secondary brain metastases that are often shielded from systemic administration of taxanes and other chemotherapeutics. Microtubule stabilization by TPI 287 may also have potential for the treatment of neurologic disorders affected by tau protein pathology. These include tauopathies such as Alzheimer’s disease and orphan diseases, such as progressive supranuclear palsy, corticobasal degeneration, and frontotemporal dementia.

About Glioblastoma

Glioblastoma (GBM) is the most aggressive and common form of brain cancer. Five-year survival after diagnosis is about 5%. The Central Brain Tumor Registry estimates that about 23,180 primary malignant brain tumors cases will be diagnosed in the US in 2015, 46% of which will be GBM. Typical front-line treatments include stereotactic or whole brain radiotherapy plus temozolomide (Temodar®). Patients with recurrent disease are candidates for treatment with Avastin®, the last FDA approved agent for this disease.

About Metastases to the Brain

According to the American Society of Clinical Oncology, approximately 25% of all cancer patients develop secondary metastases to the brain, which translates into about 400,000 cases annually in the United States. Most commonly, brain metastases originate from lung cancers (50%), breast cancers (15-20%), and melanoma (10%). Fractionated stereotactic radiotherapy (FSRT) or whole brain radiotherapy (WBRT) remains the standard of care for treatment of patients with or without surgery. Mortality rates due to brain metastases are extremely high.

About Cortice Biosciences

Cortice Biosciences, Inc. is a clinical-stage drug development company pioneering novel therapies for the treatment of oncologic and neurologic disease indications with urgent unmet medical need. More information can be found at www.corticebiosciences.com.

Safe Harbor Statement

This media release may contain forward-looking statements about Cortice Biosciences, which can be identified by the use of terminology such as "will," "would," "should," "expects," "anticipates," "intends," "plans," "believes," "may," "estimates," "predicts," "projects,” or similar expressions intended to identify such statements. These statements reflect the current views of Cortice with respect to future events, are based on assumptions, and subject to risks and uncertainties.

Cortice Biosciences, Inc. 646-747-9090 info@corticebio.com

Source: Cortice Biosciences

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