Curis & Aurigene Announce Collaboration, License & Option Agreement

Curis, Inc. and Aurigene Discovery Technologies Limited recently announced they have entered into an exclusive collaboration 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 I 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.

“We are thrilled to partner with Aurigene in seeking to discover, develop, and commercialize small molecule drug candidates generated from Aurigene’s novel technology, and we believe that this collaboration represents a true transformation for Curis that positions the company for continued growth in the development and eventual commercialization of cancer drugs,” said Ali Fattaey, PhD, President and Chief Executive Officer of Curis. “The multi-year nature of our collaboration means that the parties have the potential to generate a steady pipeline of novel drug candidates in the coming years. Addressing immune checkpoint pathways is now a well validated strategy to treat human cancers and the ability to target PD-1/PD-L1 and other immune checkpoints with orally available small molecule drugs has the potential to be a distinct and major advancement for patients. Recent studies have also shown that alterations of the MYD88 gene lead to dysregulation of its downstream target IRAK4 in a number of hematologic malignancies, including Waldenström’s Macroglobulinemia and a subset of diffuse large B-cell lymphomas, making IRAK4 an attractive target for the treatment of these cancers. We look forward to advancing these programs into clinical development later this year.”

Dr. Fattaey continued “Aurigene has a long and well-established track record of generating targeted small molecule drug candidates with biopharmaceutical collaborators, and we have significantly expanded our drug development capabilities as we advance our proprietary drug candidates in currently ongoing clinical studies. We believe that we are well-positioned to advance compounds from this collaboration into clinical development.”

CSN Murthy, Chief Executive Officer of Aurigene, added “We are excited to enter into this exclusive collaboration with Curis under which we intend to discover and develop a number of drug candidates from our chemistry innovations in the most exciting fields of cancer therapy. This unique collaboration is an opportunity for Aurigene to participate in advancing our discoveries into clinical development and beyond, and mutually align interests as provided for in our agreement. Our scientists at Aurigene have established a novel strategy to address immune checkpoint targets using small molecule chemical approaches, and have discovered a number of candidates that modulate these checkpoint pathways, including PD-1/PD-L1. We have established a large panel of preclinical tumor models in immunocompetent mice and can show significant in vivo anti-tumor activity using our small molecule PD-L1 antagonists. We are also in the late stages of selecting a candidate that is a potent and selective inhibitor of the IRAK4 kinase, demonstrating excellent in vivo activity in preclinical tumor models.”

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.

The agreement provides that the parties will collaborate exclusively in immuno-oncology for an initial period of approximately 2 years, with the option for Curis to extend the broad immuno-oncology exclusivity.

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. Fo rmore information, visit www.curis.com in the Investors section.

Modulation of immune checkpoint pathways has emerged as a highly promising therapeutic approach in a wide range of human cancers. Immune checkpoints are critical for the maintenance of self-tolerance as well as for the protection of tissues from excessive immune response generated during infections. However, cancer cells have the ability to modulate certain immune checkpoint pathways as a mechanism to evade the immune system. Certain immune checkpoint receptors or ligands are expressed by various cancer cells, targeting of which may be an effective strategy for generating anti-tumor activity. Some immune-checkpoint modulators, such as programmed death 1 (PD-1) protein, specifically regulate immune cell effector functions within tissues. One of the mechanisms by which tumor cells block anti-tumor immune responses in the tumor microenvironment is by upregulating ligands for PD-1, such as PD-L1. Hence, targeting of PD-1 and/or PD-L1 has been shown to lead to the generation of effective anti-tumor responses.

Interleukin-1 receptor-associated kinase 4, or IRAK4 is a signaling kinase that becomes inappropriately activated in certain cancers including activated B cell-diffuse large B cell lymphoma (ABC-DLBCL), an aggressive form of lymphoma with poor prognosis. There appears to be a mechanistic link with IRAK4 in ABC-DLBCL where these tumors from approximately 35% of patients harbor oncogenic mutations in the MYD88 gene, which encodes an adaptor protein that interacts directly with IRAK4. MYD88 mutations appear to constitutively activate the IRAK4 kinase complex, driving pro-survival pathways in ABC-DLBCL disease. Oncogenic MYD88 mutations have also been identified in other cancers, including in over 90% of patients with Waldenström’s Macroglobulinemia as well as in a subset of patients with chronic lymphocytic leukemia (CLL).

Curis is a biotechnology company focused on the development and commercialization of novel drug candidates for the treatment of human cancers. Curis’ pipeline of drug candidates includes CUDC-907, a dual HDAC and PI3K inhibitor, CUDC-427, a small molecule antagonist of IAP proteins, and Debio 0932, an oral HSP90 inhibitor. Curis is also engaged in a collaboration with Genentech, a member of the Roche Group, under which Genentech and Roche are developing and commercializing Erivedge, the first and only FDA-approved medicine for the treatment of advanced basal cell carcinoma.

Aurigene is a specialized, discovery stage biotechnology company, developing novel and best-in-class therapies to treat cancer and inflammatory diseases. Aurigene’s Programmed Death pathway program is the first of several immune checkpoint programs that are at different stages of discovery and preclinical development. Aurigene has partnered with several large- and mid-pharma companies in the United States and Europe and has delivered multiple clinical compounds through these partnerships. With over 500 scientists, Aurigene has collaborated with 6 of the top 10 pharma companies. Aurigene is an independent, wholly owned subsidiary of Dr. Reddy’s Laboratories Ltd. (NYSE:RDY). For more information, visit www.aurigene.com.