On March 17, 2014 Five Prime Therapeutics and Bristol-Myers Squibb Company reported that they have signed a collaboration agreement for the discovery, development and commercialization of immuno-oncology therapies directed toward targets identified in two undisclosed immune checkpoint pathways using Five Prime’s proprietary target discovery platform (Press release Bristol-Myers Squibb, MAR 17, 2014, View Source [SID:1234500292]).
Bristol-Myers Squibb will leverage Five Prime’s platform to advance its existing immuno-oncology programs by identifying the most viable drug targets for continued research and development. Drug candidates developed against these new and existing targets may be studied either as single agents or in combination with existing or potential Bristol-Myers Squibb immuno-oncology therapies.
Under the terms of the agreement, Bristol-Myers Squibb will obtain exclusive, worldwide rights to develop and commercialize products directed toward certain protein targets identified by Five Prime prior to and during the collaboration. Bristol-Myers Squibb will make an upfront payment of $20 million to Five Prime and provide up to $9.5 million in research funding over the course of the research term. Additionally, Bristol-Myers Squibb will make a payment of approximately $21 million to acquire 4.9% of Five Prime’s outstanding common stock purchased at approximately a 30% premium. Five Prime will be eligible to receive up to $300 million in future development, regulatory and sales based milestone payments per collaboration target and tiered mid-single-digit rising to low-double-digit royalty payments on net sales of each product commercialized by Bristol-Myers Squibb.

On March 13, 2014 TESARO and AnaptysBio announced an exclusive, worldwide license agreement and immuno-oncology antibody collaboration (Press release TESARO, MAR 13, 2014, View Source [SID:1234500270]). Under the terms of the agreement, TESARO receives rights to monospecific antibody drug candidates targeting TIM-3, LAG-3 and PD-1 and dual reactive antibody drug candidates targeting PD-1/TIM-3 and PD-1/LAG-3. Therapeutic antibodies selected from these programs will form the basis of a strategic platform that will enable TESARO to develop novel monotherapy and combination-based approaches with immuno-oncology and other anti-cancer agents in a variety of indications. Antibody candidates from these programs are expected to enter clinical trials over the next 18 to 24 months.
Tesaro is also interested in evaluating combinations of these antibodies with TSR-011, ALK/TRK inhibitor, and niraparib, PARP inhibitor, in addition to other anti-tumor agents with complementary mechanisms, such as immune modulating agents. The first clinical trial from this collaboration is projected to begin in mid-2015, and Tesaro expects to advance an additional candidate into clinical trials every one to two quarters thereafter.

Agreement Terms

Under the terms of this agreement with AnaptysBio, TESARO will pay an upfront license fee of $17 million, as well as provide funding of costs incurred by AnaptysBio related to the development programs. For each development program, AnaptysBio is eligible to receive milestone payments of $18 million if certain research and development events are achieved and an additional $90 million associated with certain U.S. and ex-U.S. regulatory submissions and approvals in multiple indications. AnaptysBio will also be eligible to receive tiered single-digit royalties related to worldwide net sales of products developed under the collaboration and certain commercial milestone payments if specified levels of annual worldwide net sales are attained. AnaptysBio and TESARO will together complete preclinical development of the antibody candidates, with TESARO being solely responsible for all clinical development, manufacturing, regulatory and commercial activities.

Immuno-Oncology Platform

Antibodies to immune checkpoint receptors have recently demonstrated promise in the treatment of certain solid tumors, including metastatic melanoma, renal cell carcinoma and non-small cell lung cancer. Although the normal function of immune checkpoint receptors is to maintain immune homeostasis, they are co-opted by certain tumors to evade immune surveillance. PD-1, TIM-3 and LAG-3 are each checkpoint regulators that modulate the function of the immune system via different mechanisms, and may limit the ability of the immune system to respond effectively to tumors. By blocking the interaction of PD-1, TIM-3 and LAG-3 with their respective ligands, the antibodies exclusively licensed under this collaboration aim to restore immune anti-cancer function in patients across a variety of tumor types.

PD-1, or programmed death-1, is a key immune checkpoint molecule that can limit T-cell-mediated immune responses. The presence of the PD-1 ligand, PD-L1 has been identified on many tumor types, and expression of PD-L1 has been linked to poor clinical outcomes in a variety of cancers. Anti-PD-1 antibodies have demonstrated in vivo efficacy in tumor models and have shown promising results in several clinical studies. TSR-042 is anticipated to begin clinical trials in mid-2015, and combination preclinical pharmacology studies with TSR-011, niraparib and other anti-tumor agents are planned to initiate during 2014.

TIM-3, or T-cell immunoglobulin and mucin domain-3, functions as a pattern recognition receptor that dampens the anti-tumor immune response. Anti-TIM-3 antibodies have shown preclinical anti-tumor activity and may enhance anti-tumor immunity in combination with an anti-PD-1 agent or other immune modulating molecules. In collaboration with AnaptysBio, TESARO expects to select a TIM-3 antibody for clinical development during the second quarter of 2014.

LAG-3, or lymphocyte activation gene-3, is a negative regulator of T-cell activity. Preclinical studies have demonstrated anti-tumor activity by blocking LAG-3 and PD-1 in tumor models, and LAG-3 IgG fusion protein has demonstrated promising results in clinical trials for various solid tumors. In collaboration with AnaptysBio, TESARO expects to select a LAG-3 antibody for clinical development in the third quarter of 2014.