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Epizyme Announces Tazemetostat Granted Orphan Drug Designation for Malignant Rhabdoid Tumors by U.S. FDA

On February 8, 2016 Epizyme, Inc. (NASDAQ:EPZM), a clinical stage biopharmaceutical company creating novel epigenetic therapeutics for cancer patients, reported that the United States Food and Drug Administration (FDA) has granted orphan drug status to the company’s first-in-class EZH2 inhibitor, tazemetostat, for the treatment of malignant rhabdoid tumors (MRTs) (Press release, Epizyme, FEB 8, 2016, View Source [SID:1234508999]). In December 2015, the company initiated a phase 2 study in adults and a phase 1 study in children with genetically defined tumors, including MRTs. Tazemetostat is also being investigated in an ongoing five-arm phase 2 study in patients with non-Hodgkin lymphoma.

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"Malignant rhabdoid tumors are rare and aggressive cancers with poor outcomes. There have not yet been any targeted drugs developed specifically to treat these patients," said Peter Ho, M.D., Ph.D., Chief Medical Officer, Epizyme. "In an ongoing phase 1 study, tazemetostat has demonstrated encouraging clinical activity and an acceptable safety profile in patients with these severe types of cancer. We believe tazemetostat has the potential to become an important targeted therapy for patients with MRT and we are working aggressively to execute our clinical development program."

Orphan drug designation provides the sponsor of the drug with eligibility for various development incentives, including tax credits for qualified clinical testing and marketing exclusivity for a period of seven years. Therapies with orphan drug status are also not subject to a prescription drug user fee for the orphan indication.

Currently, treatment of MRT consists of surgery, chemotherapy and radiation therapy, which are associated with limited efficacy and significant treatment-related morbidity. MRT is a tumor defined by loss of INI1 protein as measured by immunohistochemistry. Other rhabdoid tumors, such as MRT of ovary, are characterized by loss of the protein SMARCA4 and have shown sensitivity to tazemetostat in preclinical models and in our phase 1 study. The orphan drug designation applies to both INI1-negative MRT as well as SMARCA4-negative MRT of ovary.

The ongoing phase 2 adult and phase 1 pediatric studies in patients with genetically-defined solid tumors include patients with rhabdoid tumors, other INI1-negative tumors, and synovial sarcoma. Interim data from Epizyme’s registration-supporting phase 2 clinical study of tazemetostat in adult patients with genetically defined solid tumors, including MRT, other INI1-negative tumors and synovial sarcoma, are anticipated to be presented at a medical conference in late 2016.

About EZH2 in Cancer

EZH2 is a histone methyltransferase (HMT) that is increasingly understood to play a potentially oncogenic role in a number of cancers. These include non-Hodgkin lymphoma, INI1-negative cancers such as malignant rhabdoid tumors and epithelioid sarcomas, certain SMARCA4-negative solid tumors, synovial sarcoma, and a range of other solid tumors.

About Tazemetostat

Epizyme is developing tazemetostat for the treatment of patients with non-Hodgkin lymphoma and for patients with INI1-negative solid tumors, certain SMARCA4-negative solid tumors and synovial sarcoma. Tazemetostat is a first-in-class small molecule inhibitor of EZH2 created by Epizyme using its proprietary product platform. In some human cancers, aberrant EZH2 enzyme activity results in dysregulation of genes that control cell proliferation resulting in the rapid and unconstrained growth of tumor cells. Tazemetostat is the WHO International Non-Proprietary Name (INN) for compound EPZ-6438.

Additional information about this program, including clinical trial information for the adult 5-arm NHL study, can be found here: View Source

Clinical trial information for Epizyme’s ongoing phase 2 trial in adults and phase 1 trial in children with INI1-negative solid tumors, certain SMARCA4-negative solid tumors or synovial sarcoma can be found here:

View Source

View Source

CytRx Secures $40 Million Long-Term Loan Facility

On February 8, 2016 CytRx Corporation (NASDAQ: CYTR), a biopharmaceutical research and development company specializing in oncology, reported that it has entered into a long-term loan and security agreement with Hercules Technology Growth Capital, Inc. and Hercules Technology III, L.P. for up to $40 million in financing (Press release, CytRx, FEB 8, 2016, View Source;p=RssLanding&cat=news&id=2136395 [SID:1234508998]).

CytRx has received the first $25 million of financing under the loan and security agreement. The proceeds will be used for pre-commercialization and manufacturing activities for aldoxorubicin, clinical development, and general corporate purposes. A second tranche of up to $15 million will be available on or before December 31, 2016 if CytRx announces positive data from its global pivotal Phase 3 clinical trial of aldoxorubicin for the treatment of soft tissue sarcoma and initiates a clinical trial of a second novel drug candidate based on CytRx’s LADR technology platform.

"This financing is an important step for CytRx as we complete our pivotal, global Phase 3 trial with aldoxorubicin and prepare for its commercial launch," said Steven A. Kriegsman, Chairman and CEO.

"We are pleased to team up with CytRx in advance of their results from the pivotal Phase 3 clinical trial. This financing will support CytRx through this key milestone and the future launch of aldoxorubicin," said Anup Arora, Managing Director at Hercules Technology.

The financing is in the form of a 48-month term loan bearing interest at a rate of 9.5% per annum, subject to the variability of the prime interest rate. In the first year of the long-term loan, only interest is payable. If the regulatory milestone relating to data from the aldoxorubicin Phase 3 trial is positive, the interest-only period will be extended for an additional six months. If the second tranche of $15 million is funded to CytRx under the loan and security agreement, the interest-only period will be extended for another six months.

In connection with the loan and security agreement, CytRx paid and issued to the lenders certain fees of approximately $450,000 and warrants to purchase approximately 630,000 shares of common stock of CytRx at an exercise price of $2.05 per share.

Armentum Partners, through Trump Securities, LLC and Reedland Capital Partners, through Merriman Capital, Inc., a registered broker-dealer and member FINRA/SIPC, acted as financial advisors to CytRx in connection with the transaction.

ASTRAZENECA’S COMBINATION OF DURVALUMAB WITH TREMELIMUMAB SHOWS CLINICAL ACTIVITY IN NON-SMALL CELL LUNG CANCER IRRESPECTIVE OF PD-L1 STATUS

On February 8, 2016 AstraZeneca and MedImmune, its global biologics research and development arm, reported publication in The Lancet Oncology of a Phase Ib study (study 006), showing antitumour activity of combination treatment with durvalumab and tremelimumab, in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC), irrespective of PD-L1 status (Press release, AstraZeneca, FEB 8, 2016, View Source [SID:1234508997]).1

In a cohort of 26 patients treated with durvalumab 10-20 mg/kg plus tremelimumab 1 mg/kg, and followed for ≥24 weeks, the confirmed objective response rate (ORR) was 23% (95% confidence interval 9-44%).1 Comparable ORRs were seen in patients from this cohort with PD-L1 positive and negative tumours (22% and 29% respectively). Durvalumab was administered intravenously every four weeks (q4w) for 13 doses or every 2 weeks (q2w) for 26 doses, and tremelimumab was administered q4w for six doses followed by every 12 weeks (q12w) for three doses.

Data on all 56 patients treated with durvalumab 10-20 mg/kg q2w or q4w plus tremelimumab 1 mg/kg showed a manageable safety profile for an advanced NSCLC population. Thirty per cent of patients had ≥1 related Grade 3/4 adverse events (AE) and 16% discontinued treatment due to a related adverse event.

Dr Scott J. Antonia, Chair of the Department of Thoracic Oncology at Moffitt Cancer Center, Tampa, Florida, USA, said: "Combination therapy with durvalumab and tremelimumab demonstrated antitumour activity in patients with NSCLC regardless of PD-L1 status, including in patients with no evidence of tumour cell membrane PD-L1 staining. The results suggest that this combination has potential as a treatment option for patients with PD-L1 negative tumours whose needs are not addressed by currently available therapies, including immunotherapies."

With the recent introduction of checkpoint inhibitors, the presence of PD-L1 expression in a tumour is considered a significant biomarker for response to PD-L1 blockade.2 Less than half of patients with NSCLC have tumours that are PD-L1 positive,1 leaving a significant unmet medical need in the PD-L1 negative patient population.

Dr Ed Bradley, Senior Vice President, Oncology, MedImmune, said: "The newly published data are an important milestone in our scientific understanding of the patient population likely to achieve the greatest benefit from the combination of durvalumab and tremelimumab. The latest findings reinforce our belief that the combination strategy we are pursuing is key to the future success of immuno-oncology treatment."

Durvalumab is an investigational human monoclonal antibody directed against programmed death ligand-1 (PD-L1), which blocks the interactions between PD-L1 and both PD-1 and B7.1, reversing in some tumours the ability of tumour cells to avoid detection by the immune system.3 Tremelimumab inhibits the activity of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) to boost the immune response against cancer cells.4 Preclinical data suggested that targeting both PD-L1 and CTLA-4 may have additive or synergistic effects.5

A preliminary analysis of data from Study 006 was presented at the annual meeting of the Society for Immunotherapy in Cancer (SITC) (Free SITC Whitepaper), in November 2015. The Lancet Oncology publication provides a more detailed analysis with a longer follow up period and more mature data set of confirmed responses, with a focus on those which informed the selection of durvalumab 20 mg/kg plus tremelimumab 1 mg/kg, every four weeks, for ongoing Phase III trials.1

Durvalumab and tremelimumab are pipeline products under development and, as such, are not approved by the US Food and Drug Administration, European Medicines Agency or any other regulatory agency for the uses under investigation. Information regarding these investigational products should under no circumstances be regarded as a recommendation for their use or of their safety or efficacy.

– ENDS –

NOTES TO EDITORS

About durvalumab (MEDI4736)

Durvalumab is an investigational human monoclonal antibody directed against programmed death ligand-1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system.2 Durvalumab blocks these signals, countering the tumour’s immune-evading tactics.3 Durvalumab is being investigated in an extensive clinical trial programme.

About tremelimumab

Tremelimumab is a fully human anti-CTLA-4 antibody. By blocking the activity of CTLA-4, tremelimumab "releases the brakes" on T cell activation and boosts the immune response against cancer cells.4,6 In animal models, CTLA-4 blockade by anti-CTLA-4 antibodies such as tremelimumab, has been shown to promote antitumour immune responses.4 In 2015, tremelimumab was granted Orphan Drug Designation by the US Food and Drug Administration as a potential treatment for malignant mesothelioma.

CTI BioPharma Provides Update On Investigational Agent Pacritinib

On February 8, 2016 CTI BioPharma Corp. (CTI BioPharma) (NASDAQ and MTA:CTIC) reported that the Company received written communication from the U.S. Food and Drug Administration (FDA) on February 4, 2016, that the FDA has placed a partial clinical hold on the clinical studies being conducted under the Company’s Investigational New Drug ("IND") application for pacritinib (Press release, CTI BioPharma, FEB 8, 2016, View Source [SID:1234508996]) .

This clinical hold impacts part of the clinical work currently being conducted under the IND and will also affect planned clinical trials.

Under the partial clinical hold, clinical investigators may not enroll new patients or start pacritinib as initial or crossover treatment, and patients not deriving benefit after 30 weeks of pacritinib treatment should stop using pacritinib. In addition, the FDA has recommended that the Company make certain modifications of protocols, including modifying all protocols for randomized trials to disallow crossover to pacritinib, provide certain notifications, revise relevant statements in the related investigator’s brochure and informed consent documents, and take certain other actions. The Company intends to implement the FDA’s recommendations. All clinical investigators worldwide have been delivered a notice of the partial clinical hold.

The Company intends to work together with the FDA and expects to submit modifications and revisions that address the recommendations noted above. In its written notification, the FDA cited the reasons for the partial clinical hold were that there was excess mortality and other adverse events in pacritinib-treated patients compared to the control arm in the PERSIST-1 trial. The excess mortality was most evident during the non-randomized crossover period following the initial 24 weeks of randomized treatment, during which patients in the control arm could switch to pacritinib treatment. In prior correspondence, the FDA acknowledged the difficulty addressing non-significant results, and that crossover designs can confound the interpretation of safety as well as the evaluation of survival.

After submission of the required information, the FDA has indicated that it would notify the Company whether it can continue the clinical studies under the IND.

Completion of PERSIST-2 Phase 3 Trial

Additionally, CTI BioPharma announced that as of February 3, 2016, it has completed patient enrollment in the PERSIST-2 Phase 3 clinical trial of pacritinib for the treatment of patients with myelofibrosis. PERSIST-2 is evaluating pacritinib for patients with myelofibrosis whose platelet counts are less than or equal to 100,000 per microliter (≤100,000/μL). Under the FDA partial clinical hold referenced above, patients currently receiving pacritinib may continue to do so unless they are not deriving benefit after 30 weeks of pacritinib treatment, and crossover of patients from the control arm to the pacritinib arm will not be allowed.

RedHill Biopharma Announces Collaboration With Germany’s Fraunhofer Institute for Oncology Drug RP101

On February 8, 2015 RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) ("RedHill" or the "Company"), an Israeli biopharmaceutical company primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for inflammatory and gastrointestinal diseases, including cancer, reported a research collaboration with Leipzig-based Fraunhofer Institute for Cell Therapy and Immunology (IZI), a research unit of the Fraunhofer Society, one of the largest and most prominent applied research organizations in the world, for the evaluation of RedHill’s Phase II-stage oncology drug candidate, RP101(Press release, RedHill Biopharma, FEB 8, 2016, View Source [SID:1234508994]).

The research collaboration tests RP101 in pre-clinical oncology models, including pancreatic cancer, in combination with standard-of-care chemotherapies to support existing Phase I and Phase II clinical data. RP101 is a proprietary, first-in-class, orally-administered, heat shock protein 27 (Hsp27) inhibitor intended to prevent the induction of resistance to chemotherapy (chemoresistance), thus maintaining sensitivity of the tumor to chemotherapy and potentially enhancing patient survival. RP101 has completed several clinical studies, including a Phase II study in pancreatic cancer and has been granted Orphan Drug Designation for the adjunct treatment of pancreatic cancer by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

As part of the collaboration, Fraunhofer IZI is conducting real-time monitoring of tumor engraftment, tumoricidal efficacy, and response to treatment with RP101 in combination with standard-of-care chemotherapies. Results from the studies are expected during the first half of 2016. The preclinical program is intended to support the existing Phase I and Phase II clinical data with RP101 and to assess the drug’s clinical development path.

In August 2014, RedHill entered into an exclusive option agreement with RESprotect GmbH, a privately-held Germany-based biotech company, under which RedHill obtained the option to acquire the worldwide exclusive rights to RP101 for all indications, other than for the pancreatic cancer indication in South Korea. RedHill announced in July 2015 that it had extended the term of the exclusive option agreement for an additional year.

About RP101:

RP101 is a nucleoside analogue found by Prof. Rudolf Fahrig at the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM) in Hannover, Germany, to inhibit development of chemoresistance in various cancer models. It is an orally-administered, patent-protected small molecule which binds to heat shock protein 27 (Hsp27) and inhibits its anti-apoptotic effects. Hsp27 is a chaperone protein which is found in abnormally high levels in cancer cells. The overexpression of Hsp27, which results in anti-apoptotic effects, has been linked to tumor resistance to cytotoxic drugs and the development of metastasis. By inhibiting Hsp27, RP101 may prevent the induction of resistance to chemotherapy (chemoresistance) and maintain sensitivity of tumors to chemotherapy, thus potentially enhancing patient survival. RP101 has been studied in several Phase I and Phase II clinical studies with a total of 249 subjects treated, including a Phase II study in pancreatic cancer. RP101 has been granted Orphan Drug Designation for the adjunct treatment of pancreatic cancer by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).