On September 15, 2020 Exelixis, Inc. (Nasdaq: EXEL) and Iconic Therapeutics reported new preclinical data that support the continued development of ICON-2, an ADC comprised of an anti-Tissue Factor (TF) antibody and Zymeworks’ proprietary linker-payload, for the treatment of diverse solid tumors (Press release, Exelixis, SEP 15, 2020, View Source [SID1234565175]). Exelixis has an exclusive option and license agreement for ICON-2 in oncology indications under its May 2019 agreement with Iconic Therapeutics, which discovered and is developing this novel ADC. The new data, which demonstrate the superior tolerability and exposure of ICON-2 compared with an MMAE anti-TF ADC, are being presented this week in a poster at the World ADC Digital Conference, which is being held online September 15-18.

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"These data provide additional preclinical validation both of our platform of proprietary anti-TF molecules designed to efficiently but safely bind TF, which is overexpressed in a variety of solid tumors, and specifically for Iconic Therapeutics’ strategy to advance its next generation ADC targeting TF," said William L. Greene, M.D., Chief Executive Officer of Iconic Therapeutics. "Other anti-TF ADCs that use MMAE as a linker-payload have been associated with side effects that can reduce tolerability, including bleeding, neutropenia and skin toxicities. The data presented today demonstrate ICON-2 effectively kills solid tumor cells in a variety of preclinical studies with an improved tolerability profile, and support continued development of ICON-2 as a treatment for solid tumors. We are currently conducting additional preclinical and nonclinical studies in support of initiating human clinical trials of this potentially best-in-class anti-TF ADC."

TF plays a critical role in the coagulation cascade and its expression is generally restricted in normal tissue. However, solid tumors, including gastrointestinal, head and neck, cervical, ovarian and bladder tumors, frequently express TF at high levels, which is associated with poor prognosis. Although TF is an attractive target for ADC therapy, previous approaches have demonstrated the potential to interfere with the coagulation cascade and may have additional toxicities that could negatively impact their risk-benefit profile.

The data presented today include results from several preclinical studies of ICON-2. Key findings from these studies are:

ICON-2 binds to TF on human and non-human primate (NHP) cells with high affinity but does not affect coagulation as measured by FXa conversion and thrombin generation assays.
ICON-2 does not induce neutropenia in NHPs.
ICON-2 is more potent than an ADC containing MMAE conjugated to the same anti-TF antibody in mouse xenograft model of human pancreatic tumor cells.
ICON-2 is highly active in patient-derived xenograft models derived from multiple tumor types.
ICON-2 exhibits superior tolerability and exposure when compared directly with an MMAE ADC using the same anti-TF antibody in a NHP study.
"We entered into our exclusive option and license agreement with Iconic Therapeutics because its expertise in TF biology and access to proprietary ADC technology provide a robust foundation for developing potentially best-in-class therapies for solid tumor indications with significant unmet clinical need," said Peter Lamb, Ph.D., Executive Vice President, Scientific Strategy and Chief Scientific Officer of Exelixis. "The data presented today continue to support that potential and differentiate ICON-2 from other anti-TF ADCs. These promising results also underscore Exelixis’ ability to identify promising licensing opportunities as part of our ongoing pipeline expansion strategy, which includes both internally developed and in-licensed programs."

Under the terms of the May 2019 agreement, Exelixis has an exclusive option to license ICON-2 in exchange for an upfront option payment to Iconic of $7.5 million and a commitment of preclinical development funding. Exelixis can exercise its option at any time up to a potential IND application, and upon doing so would make an option exercise payment to Iconic and assume responsibilities for all subsequent clinical development and commercialization activities. Should Exelixis elect to exercise its option, Iconic will become eligible for future development, regulatory and commercialization milestone payments, as well as royalties on potential sales.