Date: 2017-01-09
Type of information: Licensing agreement
Compound: CA-170, CA-327 and CA-4948
Company: Curis (USA - MA) Aurigene (India)
Therapeutic area: Cancer - Oncology
Type agreement: development licensing collaboration
Action mechanism: immune chekpoint antagonist/kinase inhibitor. CA-170 and CA-327 are orally-available small molecule antagonist of programmed death ligand-1 (PD-L1) in the immuno-oncology field. In addition to targeting PD-L1, CA-327 also targets TIM-3, an inhibitory checkpoint molecule that plays an important role in immune suppression and is co-expressed with programmed cell death-1 (PD-1) receptors on exhausted cytotoxic T cells in tumor tissues as well as expressed on certain regulatory T cells. CA-4948 is an orally-available small molecule inhibitor of Interleukin-1 receptor-associated kinase 4 (IRAK4)
Disease:
Details: * On January 21, 2015, Curis and Aurigene announced that they have entered into an exclusive collaboration The agreement provides that the parties will collaborate exclusively in immuno-oncology for an initial period of approximately two years, with the option for Curis to extend the broad immuno-oncology exclusivity.
agreement focused on immuno-oncology and selected precision oncology targets. The collaboration provides for inclusion of multiple programs, with Curis having the option to exclusively license compounds once a development candidate is nominated within each respective program. The partnership draws from each company's respective areas of expertise, with Aurigene having the responsibility for conducting all discovery and preclinical activities, including IND-enabling studies and providing Phase 1 clinical trial supply, and Curis having responsibility for all clinical development, regulatory and commercialization efforts worldwide, excluding India and Russia, for each program for which it exercises an option to obtain a license.
The first two programs under the collaboration are an orally-available small molecule antagonist of programmed death ligand-1 (PD-L1) in the immuno-oncology field and an orally-available small molecule inhibitor of Interleukin-1 receptor-associated kinase 4 (IRAK4) in the precision oncology field. Curis expects to exercise its option to obtain exclusive licenses to both programs and file IND applications for a development candidate from each in 2015.
Financial terms: In connection with the transaction, Curis has issued to Aurigene approximately 17.1 million shares of its common stock, or 19.9% of its outstanding common stock immediately prior to the transaction, in partial consideration for the rights granted to Curis under the collaboration agreement. The shares issued to Aurigene are subject to a lock-up agreement until January 18, 2017, with a portion of the shares being released from the lock-up in four equal bi-annual installments between now and that date.
In addition Curis has agreed to make payments to Aurigene as follows:
- for the first two programs: up to $52.5 million per program, including $42.5 million per program for approval and commercial milestones, plus specified approval milestone payments for additional indications, if any;
- for the third and fourth programs: up to $50 million per program, including $42.5 million per program for approval and commercial milestones, plus specified approval milestone payments for additional indications, if any; and
- for any program thereafter: up to $140.5 million per program, including $87.5 million per program in approval and commercial milestones, plus specified approval milestone payments for additional indications, if any.
Curis has agreed to pay Aurigene royalties on any net sales ranging from high single digits to 10% in territories where it successfully commercializes products and will also share in amounts that it receives from sublicensees depending upon the stage of development of the respective molecule.
Latest news: * On January 9, 2017, Curis announced that it has exercised its option to extend the exclusivity period with Aurigene under the collaboration, license and option agreement established in January, 2015. As previously reported, the extension of exclusivity is associated with a payment of $7.5 million to Aurigene, payable in two equal installments in the first and third quarters of 2017. The collaboration between Curis and Aurigene is focused on the discovery, development and commercialization of small molecule drug candidates in the fields of immuno-oncology and selected precision oncology targets. Licensed programs within the collaboration include CA-170, a first-in-class oral, small molecule antagonist targeting programmed death ligand-1 (PD-L1) and V-domain Ig suppressor of T cell activation (VISTA) immune checkpoints that is currently being studied in a Phase 1 trial in patients with solid tumors and lymphomas; and CA-327, an oral, small molecule immune checkpoint antagonist targeting PD-L1 and T-cell immunoglobulin and mucin domain containing protein-3 (TIM-3) and CA-4948, an oral small molecule inhibitor of Interleukin-1 receptor-associated kinase 4 (IRAK4), both of which are currently completing IND-enabling studies. * On October 11, 2016, Curis announced the expansion of its pipeline with CA-327, an oral, small molecule immune checkpoint antagonist targeting programmed death ligand-1 (PD-L1) and T-cell immunoglobulin and mucin domain containing protein-3 (TIM-3). Curis licensed the PD-1/ TIM-3 antagonist program, and designated CA-327 as the development candidate, by exercising its option under the collaboration, license and option agreement established with Aurigene in January 2015. * On October 19, 2015, Curis announced the expansion of its pipeline with the addition of two programs, the first of which is an oral, small molecule immune checkpoint antagonist targeting programmed death ligand-1 (PD-L1) and V-domain Ig suppressor of T cell activation (VISTA), and the second is focused on inhibitors of Interleukin-1 receptor-associated kinase 4 (IRAK4).Curis exercised its option to exclusively license a first-in-class oral, small molecule antagonist designated as CA-170 that targets PD-L1 and VISTA, which function as negative checkpoint regulators of immune activation. CA-170 was selected from the broad PD-L1 antagonist program that the companies have been engaged in since the collaboration was established in January 2015. Curis also exercised its option to exclusively license a program of orally available small molecule inhibitors of IRAK4 kinase. IRAK4 is a serine/ threonine kinase involved in the regulation of innate immune responses and also plays an important role in certain hematologic cancers. IRAK4 is inappropriately activated, and drives pro-survival and cytokine mediated pathways in cancers such as activated B cell-diffuse large B cell lymphoma (ABC-DLBCL), an aggressive form of lymphoma with poor prognosis. Targeting IRAK4 has potential therapeutic implications in both cancer and cytokine-driven inflammatory and autoimmune diseases.
The exercise of options for the PD-L1/VISTA and IRAK4 programs resulted in an aggregate one-time payment of $6 million by Curis to Aurigene in exchange for an exclusive, royalty-bearing license to develop, manufacture and commercialize compounds from the programs, including the development candidate, CA-170 and products containing such compounds, anywhere in the world with the exception of India and Russia, where Aurigene will hold an exclusive, royalty-free, fully paid license to commercialize such compounds.
