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.

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.

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.