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Exelixis announced "positive" phase 1b clinical trial results for the combination of cabozantinib and atezolizumab in patients with locally advanced or metastatic solid tumors. Data from two expansion cohorts of the COSMIC-021 trial was presented during the European Society for Medical Oncology, or ESMO, Virtual Congress 2020. Results from the clear cell renal cell carcinoma cohort are being presented in the GU Proffered Paper Session on September 21, and results from the non-clear cell RCC cohort were presented as a poster available on demand for registrants beginning September 17, the company noted. "Given the broad experience with cabozantinib as monotherapy for advanced kidney cancer, it's very exciting to see the growing body of clinical evidence that demonstrates encouraging tolerability and clinical activity when combining cabozantinib with atezolizumab in this disease. We are especially encouraged to see a durable objective response in more than 50% of patients with previously untreated clear cell RCC, paired with an acceptable safety profile at both cabozantinib dose levels evaluated in combination with atezolizumab. We look forward to learning more about the potential of this combination regimen to improve outcomes for patients with advanced kidney cancer from the ongoing phase 3 CONTACT-03 trial," said Dr. Sumanta Pal, Clinical Professor, City of Hope, the principal investigator for the COSMIC-021 study.

Bristol Myers Squibb (BMY) and Exelixis (EXEL) have announced the first presentation of results from the pivotal Phase 3 CheckMate -9ER trial, in which Opdivo in combination with CABOMETYX demonstrated "significant improvements" across all efficacy endpoints, including overall survival, in previously untreated advanced renal cell carcinoma. Opdivo in combination with CABOMETYX reduced the risk of death by 40% vs. sunitinib. In patients receiving Opdivo in combination with CABOMETYX, median progression-free survival, the trial's primary endpoint, was doubled compared to those receiving sunitinib alone: 16.6 months vs. 8.3 months, respectively. In addition, Opdivo in combination with CABOMETYX demonstrated a superior objective response rate, with twice as many patients responding compared to sunitinib, and 8% vs. 5% achieved a complete response. Opdivo in combination with CABOMETYX was associated with a longer duration of response than sunitinib, with a median duration of 20.2 months vs. 11.5 months. All of these key efficacy results were consistent across the pre-specified International Metastatic Renal Cell Carcinoma Database Consortium risk and PD-L1 subgroups. Opdivo combined with CABOMETYX was well tolerated and reflected the known safety profiles of the immunotherapy and tyrosine kinase inhibitor components in previously untreated advanced RCC. The incidence of treatment-related adverse events, including any-grade and high-grade TRAEs, was slightly higher for Opdivo in combination with CABOMETYX vs. sunitinib, with a low rate of treatment-related discontinuations. Patients treated with Opdivo in combination with CABOMETYX reported significantly better health-related quality of life than those treated with sunitinib at most time points, according to National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy Kidney Symptom Index 19 scores. Based on these efficacy and safety results from CheckMate -9ER, Bristol Myers Squibb and Exelixis' partner Ipsen (IPSEY), which has exclusive rights to commercialize and develop CABOMETYX outside of the U.S. and Japan, each submitted type II variation applications for Opdivo plus CABOMETYX to the European Medicines Agency. On September 12, the EMA validated the type II variations, confirming the submissions are complete and beginning the EMA's centralized review process. In addition, Bristol Myers Squibb and Exelixis recently completed their respective U.S. Food and Drug Administration submissions for Opdivo in combination with CABOMETYX and, along with their partners, plan to discuss the CheckMate -9ER data with regulatory authorities across the world.

Ipsen (IPSEY) announced the first presentation of results from the pivotal Phase III CheckMate -9ER trial, in which Cabometyx in combination with Bristol Myers Squibb's (BMY) Opdivo demonstrated "significant improvements" across all efficacy endpoints, including overall survival, in previously untreated advanced renal cell carcinoma. Cabometyx in combination with Opdivo reduced the risk of death by 40% versus sunitinib. In patients receiving Cabometyx in combination with Opdivo, median progression-free survival, the trial's primary endpoint, was doubled compared to those receiving sunitinib alone: 16.6 months versus 8.3 months respectively. In addition, Cabometyx in combination with Opdivo demonstrated a superior objective response rate, with twice as many patients responding compared to sunitinib, and 8% versus 5% achieved a complete response. Cabometyx in combination with Opdivo was associated with a longer duration of response than sunitinib, with a median duration of 20.2 months versus 11.5 months. Additionally, patients treated with the combination had a much lower rate of treatment discontinuation versus sunitinib, and a significantly lower rate of treatment discontinuation due to disease progression versus sunitinib. All key efficacy results were consistent across the pre-specified International Metastatic Renal Cell Carcinoma Database Consortium risk and PD-L1 subgroups. Cabometyx in combination with Opdivo was well tolerated and reflected the known safety profiles of the immunotherapy and tyrosine kinase inhibitor components in previously untreated advanced RCC. The incidence of treatment-related adverse events, including any-grade and high- grade TRAEs, was slightly higher for Cabometyx in combination with Opdivo versus sunitinib, with a low rate of treatment- related discontinuations. Patients treated with Cabometyx in combination with Opdivo reported significantly better health-related quality of life than those treated with sunitinib at most time points, according to National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy-Kidney Symptom Index 19 scores. Based on these efficacy and safety results from CheckMate -9ER, Ipsen and Bristol Myers Squibb have each submitted type II variation applications for Cabometyx in combination with Opdivo to the European Medicines Agency. On September 12, the EMA validated the type II variations, confirming the submissions are complete and beginning the EMA's centralized review process. In addition, Bristol Myers Squibb and Exelixis (EXEL), which has exclusive rights to commercialize and develop Cabometyx in the U.S., recently completed their respective U.S. FDA submissions for Cabometyx in combination with Opdivo and for Opdivo in combination with Cabometyx, and along with their partners, they plan to discuss the CheckMate -9ER data with regulatory authorities across the world.

Exelixis and Iconic Therapeutics announced new preclinical data that support the continued development of ICON-2, an ADC comprised of an anti-Tissue Factor, or TF, antibody and Zymeworks' proprietary linker-payload, for the treatment of diverse solid tumors. 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. TF plays a 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 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, or 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. 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 $7.5M 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.

Exelixis (EXEL) and Catalent (CTLT) announced a partnership under which Catalent's Redwood Bioscience subsidiary will develop multiple antibody-drug conjugates, or ADCs, for Exelixis using Catalent's proprietary SMARTag site-specific bioconjugation technology. Under the terms of the agreement, Catalent will use its SMARTag bioconjugation platform to build ADCs using monoclonal antibodies, or mAbs, from Exelixis' growing preclinical pipeline. In exchange for an upfront payment to Catalent of $10M, Exelixis received an exclusive option to nominate up to a fixed number of targets using the SMARTag ADC platform over a three-year period. The companies plan to advance the ADCs into preclinical development, and, prior to filing an Investigational New Drug application, Exelixis may exercise its exclusive option to a worldwide license of the related ADC program and continue clinical development and commercialization. Exelixis will provide research and development funding, and Catalent will be eligible for development and commercial milestones and royalties on net sales of any product commercialized as part of the collaboration.

Exelixis and NBE-Therapeutics announced a partnership to discover and develop multiple antibody-drug conjugates, or ADCs, for oncology applications by leveraging NBE's expertise and proprietary platforms in ADC discovery, including site-specific conjugation and novel payloads. The agreement comes as Exelixis continues to build out its pipeline behind Cabometyx, its product that is now a global oncology franchise. Under the terms of the agreement, Exelixis will make an upfront payment of $25M to NBE in exchange for an exclusive option to nominate a defined number of target programs on NBE's ADC platform over a two-year period. Together, the companies will seek to advance multiple ADCs into preclinical development with Exelixis contributing research and development support. For each individual target program, prior to filing an Investigational New Drug application, Exelixis will be able to exercise its option to an exclusive worldwide license, and afterwards continue clinical development and commercialization activities for that target program. Upon exercise of any option, NBE will be eligible for development and commercialization milestones, as well as royalties on net sales of any potential products resulting from that target program.