Therapy Areas: Respiratory
Exelixis In-Licenses Second Anti-Cancer Compound from Aurigene Following FDA Acceptance of Investigational New Drug Application for Phase 1 Clinical Trial in Non-Hodgkin's Lymphoma
15 October 2021 - - US-based Exelixis, Inc. (NASDAQ: EXEL) has exercised its exclusive option under its July 2019 agreement with Aurigene Discovery Technologies Ltd. to in-license XL114 (formerly AUR104), a novel anti-cancer compound that inhibits the CARD11-BCL10-MALT1 signaling pathway, which promotes lymphocyte survival and proliferation, the companies said.

Exelixis has now assumed responsibility for the future clinical development, commercialization and global manufacturing of XL114.

Following the US Food and Drug Administration's recent acceptance of its Investigational New Drug application, Exelixis will soon initiate a phase 1 clinical trial evaluating XL114 monotherapy in patients with Non-Hodgkin's lymphoma.

At the American Association of Cancer Research annual meeting in April of this year, Aurigene presented preclinical data (Abstract 1266) demonstrating that XL114 exhibited potent anti-proliferative activity in a large panel of cancer cell lines ranging from hematological cancers to solid tumors with excellent selectivity over normal cells.

In addition, oral dosing of XL114 resulted in significant dose-dependent tumor growth inhibition in diffuse large B-cell lymphoma (DLBCL) and colon carcinoma models.

XL114 is the second molecule that Exelixis in-licensed from Aurigene under the companies' July 2019 collaboration, option and license agreement.

Exelixis previously exercised its option to in-license XL102, a potent, selective and orally bioavailable inhibitor of cyclin-dependent kinase 7, from Aurigene in December 2020 and initiated a phase 1 trial of XL102 as a single agent and in combination with other anti-cancer agents in patients with advanced or metastatic solid tumors in January 2021.

XL114 was identified to have anti-proliferative activity in cell lines with constitutive activation of CBM signaling, including activated B-cell-like DLBCL (ABC-DLBCL), mantle cell lymphoma and follicular lymphoma cell lines.

Further characterization of XL114 in cell-based assays demonstrated a functional role in B-cell signaling pathways.

Additionally, XL114 showed dose-dependent tumor growth inhibition in an ABC-DLBCL mouse xenograft tumor model.

In preclinical development, XL114 also demonstrated a high degree of selectivity against a broad safety pharmacology panel of enzymes and receptors.

While the precise molecular mechanism underlying XL114's function in repressing BCR signaling and MALT1 activation has yet to be characterized, the fatty acid-binding protein 5 (FABP5) has been identified as a prominent XL114-binding target.

Under the terms of the July 2019 agreement, Exelixis made an upfront payment of USD10 m for exclusive options to obtain an exclusive license from Aurigene to three preexisting programs, including the compounds now known as XL102 and XL114.

In addition, Exelixis and Aurigene initiated three Aurigene-led drug discovery programs on mutually agreed upon targets, in exchange for an additional upfront payment of USD 2.5m per program.

The collaboration was expanded in 2021 to include three additional early discovery programs. Exelixis is also contributing research funding to Aurigene to facilitate discovery and preclinical development work on all nine programs.

Exelixis may exercise its option for a program at any time up until the first IND for the program becomes effective.

Having exercised options on two programs thus far (XL102 and XL114), if and when Exelixis exercises a future option, it will make an option exercise payment to Aurigene and assume responsibility for that program's future clinical development and commercialization including global manufacturing.

To exercise its option for XL114, Exelixis will make an option exercise payment to Aurigene of USD 10m.

Once Exelixis exercises its option for a program, Aurigene will be eligible for clinical development, regulatory and sales milestones, as well as royalties on future potential sales of the compound. Under the terms of the agreement, Aurigene retains limited development and commercial rights for India and Russia.

Aurigene Discovery Technologies Ltd. is a development stage biotech company engaged in discovery and clinical development of novel and best-in-class therapies to treat cancer and inflammatory diseases and a wholly owned subsidiary of Dr. Reddy's Laboratories Ltd. (BSE: 500124) (NSE: DRREDDY) (NYSE: RDY) (NSEIFSC: DRREDDY).

Aurigene is focused on precision-oncology, oral immune checkpoint inhibitors, and the Th-17 pathway.

Aurigene's programs currently in clinical development include an oral ROR-gamma inhibitor AUR101 for moderate to severe psoriasis in phase 2 under a US FDA IND and a PD-L1/VISTA antagonist CA-170 for non-squamous non-small cell lung cancer in phase 2b/3 in India.

Additionally, Aurigene has multiple compounds at different stages of pre-clinical development.

Aurigene has also partnered with several large and mid-pharma companies in the US and Europe and has multiple programs in clinical development.

Founded in 1994, Exelixis, Inc. (NASDAQ: EXEL) is an oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers.
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