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Chipscreen Biosciences Announces CFDA Approval of Chidamide (Epidaza) for PTCLs in China

On January 9, 2015 Chipscreen Biosciences reported regulatory approval of Chidamide (Epidaza), the world first orally administrated and subtype-selective histone deacetylase (HDAC) inhibitor for relapsed or refractory peripheral T-cell lymphoma (PTCL) patients, in China on Dec. 23, 2014 by the Chinese Food and Drug Administration (CFDA) (Press release, Shenzhen Chipscreen Biosciences, JAN 9, 2015, View Source [SID1234551991]).

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Peripheral T-cell lymphomas (PTCL) is a set of rare and heterogeneous group of mature T- and natural killer (NK)-cell neoplasms associated with poor outcome. PTCL makes up 25 percent to 30 percent of all Non-Hodgkin’s lymphoma (NHL) cases in China, much higher than that seen in Western countries of 10 percent to 15 percent. The subtype distribution of PTCL is also significantly different between China and Western countries, in which extranodal NK/T-cell lymphoma, nasal type (ENKL), a subtype highly aggressive with very poor prognosis, to be the leading subtype in Chinese population.

"Chidamide is the first new molecular entity discovered and developed by Chipscreen scientists in China. The CFDA’s decision to approval the world first orally administrated selective HDACi for PTCLs is an important validation of the drug’s therapeutic potential for this urgent medical need for Chinese PTCLs patients. The orally administrated Chidamide not just will provide affordable innovative treatment for the Chinese patients whom otherwise have no option to obtain most up-to-dated new treatment beyond conventional chemotherapies, but also have great potential, based on its unique epigenetic mechanism of actions and existing knowledge from the field, to be easily combined with other treatment modalities in comprehensive control and management of cancer patients in fight against drug resistance and tumor recurrence," said Xian-Ping LU, Ph.D., Chief Executive Officer and Chief Scientific Officer of Chipscreen Biosciences Ltd.

About Chidamide (Epidaza)

Chidamide is an orally bioavailable, low-nanomolar inhibitor of cancer-associated histone deacetylase (HDAC) enzymes with favorable pharmacology and tolerability profiles relative to existing benzamide and non-benzamide HDAC inhibitors. It targets specifically the subtype 1, 2, 3 of Class I and subtype 10 of Class IIb HDAC and is being studied in multiple clinical trials as a single agent or in combination with chemotherapeutic agents for the treatment of various hematological and solid cancers. In clinically administrated concentrations, it demonstrated a unique epigenetic mechanism of actions against tumor cell development, involving preferential induction of growth arrest and apoptosis in blood and lymphoid-derived tumor cells, activation of NK-mediated and CD8-mediated antigen-specific cellular anti-tumor immunity, differentiation of tumor stem cells, reversal of drug-resisting tumor cells and epithelia to mesenchymal transition, which are hallmarks of treatment resistance, tumor cell metastasis and recurrence.

Information about Chidamide: www.epidaza.com

Incyte and Agenus Announce Global Alliance to Develop Novel Immuno-Oncology Antibodies

On January 9, 2015 Incyte reported a global license, development and commercialization agreement focused on novel immuno-therapeutics using Agenus’ proprietary Retrocyte Display antibody discovery platform (Press release Agenus, JAN 9, 2015, View Source [SID:1234501312]).

The alliance will initially focus on the development of checkpoint modulator antibodies directed against GITR, OX40, LAG-3 and TIM-3. Agenus and Incyte will share all costs and profits for the GITR and OX40 antibody programs on a 50:50 basis, with Agenus eligible for potential milestones; TIM-3 and LAG-3 are royalty-bearing programs to be funded by Incyte, with Agenus eligible for potential milestones and royalties. The first clinical trials are expected to be initiated in 2016.

“This alliance with Agenus adds therapeutic antibody capabilities to our proven small molecule discovery expertise, significantly expands the landscape of potential immuno-oncology targets available to us, and strengthens our ability to identify and advance novel therapeutic combinations,” said Hervé Hoppenot, President and CEO of Incyte.

“Incyte’s track record of success in oncology development and commercialization, together with our therapeutic antibody expertise and the commonality of our objectives, speak to the compelling strategic rationale for this alliance,” said Garo H. Armen, Ph.D., Chairman and CEO of Agenus. “Our Retrocyte Display technology has produced high quality antibody candidates and offers significant advantages over competing technologies. With Incyte, we believe we have an ideal partner to help define the evolving treatment paradigm of cancer immunotherapies.”

Under the terms of the agreements between the parties, Incyte will make upfront payments to Agenus totaling $25 million and invest $35 million by purchasing approximately 7.76 million newly issued shares of Agenus common stock at a price of $4.51 per share. In addition to the initial four target programs in the alliance, the parties have an option to jointly nominate and pursue additional targets within the framework of the multi-year collaboration. Terms also include:

For each royalty-bearing product, Agenus will be eligible to receive up to $155 million in future contingent development, regulatory and commercialization milestones.
Also for royalty-bearing products, Agenus will be eligible to receive tiered royalties on global net sales ranging from mid-single to low-double digit rates, and has reserved the right to elect to co-fund 30% of development costs for increased royalties.
For products from any additional programs that the parties elect to bring into the collaboration, Agenus may opt to designate them as profit-share products.
For each profit-share product, Agenus will be eligible to receive up to $20 million in future contingent development milestones.

Retrocyte Display is a proprietary retroviral technology that enables a highly diverse library (>1×109) of human IgG molecules to be displayed on the surface of B-lineage cells. This innovative cell-displayed expression platform permits the rapid generation of fully human and humanized therapeutic antibodies with high affinity and target specificity.

The closing of the transaction is conditioned on the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.

AVEO Receives Confirmation of Eligibility for Submission of a Tivozanib Marketing Authorization Application to the European Medicines Agency

On January 8, 2015 AVEO Oncology reported that it has received written confirmation from the European Medicine Agency (EMA) that tivozanib is eligible for submission of an application for a European Union Marketing Authorization under the Agency’s centralized procedure (Press release AVEO, JAN 8, 2015, View Source;p=RssLanding&cat=news&id=2004942 [SID:1234501284]). Confirmation of eligibility was given in response to the submission of a letter of intent enabling the Company to evaluate the opportunity for submitting a Marketing Authorization Application (MAA) for tivozanib with the EMA for the treatment of renal cell carcinoma (RCC). Tivozanib is an oral, potent, selective inhibitor of vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI) with a long half-life and activity against all three VEGF receptors. Tivozanib has previously been granted orphan drug designation in Europe for the treatment of RCC.

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The letter of intent, which must be filed at least seven months prior to submission of a MAA, initiates the process to address a number of pre-submission requirements, including the assignment of a Rapporteur and Co-Rapporteur, who are two appointed members of the Committee for Human Medicinal Products (CHMP). The CHMP is the committee responsible for preparing opinions on questions concerning human medicines. Confirmation of eligibility for submission is not predictive of the EMA’s approval of a MAA.

"Our letter of intent and the subsequent confirmation of eligibility by the EMA are first steps in evaluating the potential for submission of a tivozanib MAA in Europe for the treatment of RCC," said Michael Bailey, president and chief executive officer of AVEO. "AVEO and its global RCC clinical advisors continue to believe that tivozanib has the potential to offer RCC patients an alternative to existing therapies. With the European rights to tivozanib recently regained, we now have the opportunity to work with the EMA to fully evaluate the potential for a MAA submission."

AVEO remains encouraged by the clinical outcomes from its Phase 2 and Phase 3 studies in RCC and the efficacy and tolerability profile that tivozanib may offer to patients suffering from this challenging disease. AVEO recently entered into an option agreement with Ophthotech to investigate tivozanib for the potential treatment of non-oncologic diseases of the eye, and the Company is actively pursuing partnerships to advance the development of tivozanib in solid tumors.

Pfizer Provides Update on IBRANCE® (palbociclib)

On January 8, 2015 Pfizer reported that The U.S. Food and Drug Administration (FDA) has informed Pfizer that at this time there is no plan for an Oncologic Drugs Advisory Committee meeting for IBRANCE (palbociclib) (Press release Pfizer, JAN 8, 2015, View Source [SID:1234501294]). Pfizer continues to have an open and productive dialogue with the FDA as the application for IBRANCE advances. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is April 13, 2015. The Company reports that it has entered label discussions with the FDA and hopes to be able to bring IBRANCE to patients who need it as soon as possible.

CytRx Announces Positive Interim Phase 2 Aldoxorubicin Results as a Treatment for HIV-Related Kaposi’s Sarcoma (KS)

On January 8, 2015 CytRx Corporation reported positive interim results from its ongoing Phase 2 clinical trial evaluating the safety and efficacy of aldoxorubicin for the treatment of Kaposi’s Sarcoma (KS) in HIV-infected patients (Press release CytRx, JAN 8, 2015, View Source [SID:1234501287]). The clinical results reported are from 9 patients, 6 of which carried the worst KS prognosis. Also, 4 of the 9 patients had received from 1 to 8 prior liposomal doxorubicin (Doxil) cycles. Efficacy results revealed that all 9 patients (100%) exhibited a decrease in skin lesions and in the number of cancer cells expressing the KS virus DNA. Of the 6 patients with lung tumors, 4 patients (66%) demonstrated either a partial or complete response, with no patients (0%) demonstrating progression. Data thus far show that aldoxorubicin can be detected in all tumor biopsies 24 hours following drug administration. Preliminary safety results showed only 2 patients (22%) experienced a grade 4 adverse event (transient neutropenia and anemia). Other adverse events were mild and most were unrelated to aldoxorubicin.

“The current standard-of-care for severe dermatological and systemic KS is Doxil, however, many patients experience significant toxicity, or exhibit minimal to no clinical response to this agent,” said Steven Kriegsman, Chairman and CEO of CytRx. “Aldoxorubicin has demonstrated effectiveness against a range of tumors in the phase 2 clinical trial, thus we are optimistic in regard to its potential as a treatment for KS. This data provides important insight into both the safety and efficacy of aldoxorubicin in this indication, and the lack of toxicity of our drug in these patients is very impressive. We look forward to further data using aldoxorubicin in KS as this study continues.”

Assuming a positive outcome of the ongoing Phase 2 clinical trial, CytRx plans to discuss with the FDA a potential pathway for the registration of aldoxorubicin for use in KS. The Company intends to submit the Phase 2 KS data for presentation at the 2015 ASCO (Free ASCO Whitepaper) annual meeting.

This open-label Phase 2 clinical trial is expected to enroll up to 30 patients, randomly assigned to three equally sized treatment arms which will receive aldoxorubicin at 50, 100 or 150 mg/m2 by 30-minute intravenous infusion. Because the KS patients in the study have compromised immune systems, the aldoxorubicin dosages administered in the trial are lower than those administered in the Company’s clinical testing of aldoxorubicin in patients with soft tissue sarcomas. Patients with advanced KS receive aldoxorubicin on day 1, then every 3 weeks until evidence of tumor progression, unacceptable toxicity or withdrawal of consent. The primary objectives of preliminary efficacy include evaluation of the size, number and nodularity of skin lesions, change in size and number of lung lesions and changes in the number of tumor cells that express the KS virus DNA (Human Herpes Virus 8). The Company is also evaluating the level of aldoxorubicin uptake into lesions. Safety is being assessed through monitoring of adverse events and the ability to remain on assigned treatment. The trial is being conducted at the Louisiana State University Health Sciences Center in New Orleans, LA. Possible additional sites are being considered to expedite enrollment.

KS is an orphan indication in the U.S.