On September 9, 2024 Agenus Inc. ("Agenus") (Nasdaq: AGEN), a leader in developing novel immunological agents to treat various cancers, reported that updated data from the clinical trial of botensilimab and balstilimab in refractory sarcomas will be featured in a mini oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, taking place September 13-17, 2024, in Barcelona, Spain (Press release, Agenus, SEP 9, 2024, View Source [SID1234646461]).

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The presentation will feature updated efficacy and safety data from the large, ongoing Phase 1 trial, highlighting the potential of this combination therapy in treating patients with refractory sarcomas, including visceral angiosarcoma and leiomyosarcoma, populations with limited therapeutic options. Botensilimab, a novel investigational Fc-enhanced CTLA-4 inhibitor, and balstilimab, an investigational PD-1 antibody, have shown promising clinical responses in multiple tumor types, including "cold" tumors that are typically unresponsive to standard therapies.

Presentation Details:

Abstract Title: Updated efficacy and safety of botensilimab plus balstilimab in patients with refractory metastatic sarcoma from an expanded phase 1 study

Abstract Number: 1726MO

Presenting Author: Breelyn A. Wilky, MD, University of Colorado Cancer Center

Session: Mini Oral Session, Sarcoma

Session Date and Time: Friday, September 13th, 2024, at 4:00 p.m. – 5:30 p.m. CEST (10:00 a.m. – 11:30 a.m. ET)

Complete abstracts are available through the ESMO (Free ESMO Whitepaper) Congress program. The presentation will also be available in the publications section of the Agenus website following the ESMO (Free ESMO Whitepaper) Congress on Friday, September 13th.

About Botensilimab

Botensilimab is an investigational human Fc enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to "cold" tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.

Approximately 1,100 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.

On September 9, 2024 Nuvation Bio Inc. (NYSE: NUVB), a late clinical-stage, global biopharmaceutical company tackling some of the greatest unmet needs in oncology, reported that David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio, will present at the Cantor Global Healthcare Conference in New York, NY on Thursday, September 19, 2024, at 9:45 a.m. E.T (Press release, Nuvation Bio, SEP 9, 2024, View Source [SID1234646460]).

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A live webcast of the presentation will be available on the Nuvation Bio website at View Source An archived recording will be available for 90 days following the event.

On September 9, 2024 Bayer reported encouraging results from the expansion part of the ongoing Phase I/II SOHO-01 study evaluating the safety and preliminary efficacy of BAY 2927088 in advanced HER2-mutant non-small cell lung cancer (NSCLC). Data were presented during the Presidential Symposium at the IASLC 2024 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer, taking place in San Diego, United States, from September 7-10, 2024 (Press release, Bayer, SEP 9, 2024, View Source [SID1234646459]).

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"The encouraging results from the expansion phase of the SOHO-01 trial demonstrate the potential of this targeted therapy to advance outcomes for patients with HER2-mutant NSCLC, a type of lung cancer with limited treatment options and poor prognosis," said Christian Rommel, Ph.D., Head of Research and Development at Bayer’s Pharmaceuticals Division. "The development of BAY 2927088 underscores our ongoing commitment in lung cancer and our continued drive to develop precise and personalized healthcare solutions in disease areas with the highest unmet needs."

"HER2-mutant NSCLC is a challenging disease that can predominantly affect individuals who are young and never smoked a cigarette. Given the current lack of therapeutic options, there is an immediate need for effective, manageable treatments," said SOHO-01 lead trialist, Xiuning Le, MD, PhD, The University of Texas MD Anderson Cancer Center, Houston, TX. "BAY 2927088 showed promising preliminary efficacy in both response rate and duration, and a manageable safety profile, which emphasizes the importance of ongoing innovation to elevate the standard of care."

The objective of the expansion phase of the study was to determine the safety, tolerability, and pharmacokinetics of BAY 2927088 in patients with HER2-mutant NSCLC. These data support the ongoing investigation of BAY 2927088 in patients with advanced NSCLC harboring HER2 mutations. Just recently Bayer announced that the first patient has been enrolled in the global Phase III SOHO-02 trial, an open-label, randomized, multicenter clinical trial, assessing the efficacy and safety of investigational agent BAY 2927088 as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC), whose tumors have activating HER2 mutations.

Detailed Results from SOHO-01
SOHO-01 is an ongoing, open-label, multicenter Phase I/II study. Results from patients with advanced NSCLC harboring a HER2-activating mutation with disease progression after ≥1 systemic therapies for advanced disease, and who are naïve to HER2-targeted therapy were presented. In the trial, patients received oral BAY 2927088 20 mg twice daily. Forty-three out of forty-four patients enrolled were evaluable for efficacy, with a confirmed objective response rate (ORR) of 72.1% (n=31; 95% CI 56.3, 84.7) including 1 complete response (2.3%). Median duration of response (DOR) and progression-free survival (PFS) were 8.7 months (95% CI 4.5, not estimable) and 7.5 months (95% CI 4.4, 12.2), respectively. In patients with HER2 YVMA insertions, the most frequent mutation, ORR was 90.0%, DoR was 9.7 months, and PFS was 9.9 months.

The safety profile of BAY 2927088 was found to be manageable, and consistent with previous reports. Treatment-related adverse events (TRAEs) were reported in 95.5% of patients, with grade 3 TRAEs reported in 40.9%. Diarrhea was the most common TRAE (86.4%, 25.0% grade 3), followed by rash (43.2% grade 1 or 2) and paronychia (25.0% grade 1 or 2). Three patients (6.8%) discontinued due to TRAEs.

About BAY 2927088
BAY 2927088 is an investigational agent and has not been approved by any health authority for use in any country, for any indication. It is currently being evaluated as a potential new targeted treatment option for patients with NSCLC harboring HER2 activating mutations. BAY 2927088 is an oral, reversible tyrosine kinase inhibitor (TKI) that potently inhibits mutant human epidermal growth factor receptors 2 (HER2), including HER2 exon 20 insertions and HER2 point mutations, as well as epidermal growth factor receptors (EGFR), with high selectivity for mutant vs wild-type EGFR. Investigational agent BAY 2927088 is derived from Bayer’s strategic research alliance with the Broad Institute of MIT and Harvard in Cambridge, MA, USA.

About Breakthrough Therapy Designation
This Breakthrough Therapy designation for BAY 2927088 is supported by preliminary clinical evidence from the Phase I/II, open-label, multicenter first-in-human study (NCT05099172) evaluating the safety, pharmacokinetics and preliminary efficacy of BAY 2927088 in adult patients with advanced NSCLC harboring HER2 or EGFR. The Breakthrough Therapy designation is a process designed to expedite the development and review of novel medicines that are intended for the prevention or treatment of serious, life-threatening diseases or conditions that severely impact the quality of life for which there is no existing treatment, or where sufficient evidence indicates advantages of the novel drug over available treatment options.

About Non-Small Cell Lung Cancer (NSCLC)
Lung cancer is the leading cause of cancer-related deaths worldwide. NSCLC is the most common type of lung cancer, accounting for more than 85% of cases. Activating HER2 mutations are found in 2% to 4% of advanced NSCLC. 80% of people diagnosed with NSCLC have already progressed to advanced stages, which makes it more difficult to treat. Patients with HER2-mutant NSCLC currently face limited treatment options, highlighting an urgent need for more effective therapies.

On September 9, 2024 Cellworks Group Inc., a leader in Personalized Therapy Decision Support and Precision Drug Development, reported findings from a study using the Cellworks Platform to predict the benefits of adding chemotherapy to osimertinib treatment in patients with EGFR mutated non-small cell lung cancer (NSCLC) (Press release, Cellworks, SEP 9, 2024, View Source [SID1234646458]). Leveraging data from a real-world retrospective cohort, the biosimulation study confirmed that adding chemotherapy to osimertinib led to a higher predicted overall response rate (ORR). The study revealed that while all patients responded to the addition of chemotherapy, the magnitude of benefit varied among individuals and was intricately determined by underlying genomic abnormalities, enabling the identification of patients who would benefit from combination therapies, and others who would achieve similar outcomes without the addition of chemotherapy.

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Results from the study were showcased in a poster presentation (P1.06A.03) titled ‘Use of Biosimulation to Predict Concomitant Chemotherapy Benefit in NSCLC Patients with EGFR Mutations Being Treated with Osimertinib’ as part of the IASLC 2024 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer in San Diego, California on September 8, 2024.

"Osimertinib has become a standard treatment option in patients with NSCLC harboring EGFR mutations," said Dr. Charu Aggarwal, MD, MPH, Professor of Medicine, University of Pennsylvania, Associate Director, PC3I and Director, Program in Precision Oncology Innovation, Penn Center for Cancer Care Innovation; and Principal Investigator for the study. "However, while targeted therapies are generally effective for these patients, response rates can vary significantly, and the potential advantage of incorporating chemotherapy in some patients remains unclear. This study demonstrates how utilizing Cellworks biosimulation can provide valuable insights by more accurately predicting the benefit of chemotherapy, as it allows for a deeper understanding of an individual patient’s therapy response based on biosimulation of their full mutation profile."

"This study opens new potential avenues for optimizing treatment strategies in NSCLC patients with EGFR mutations," said Dr. Michael Castro, Cellworks Chief Medical Officer. "By identifying additional biomarkers that influence chemotherapy response in NSCLC patients, we gain a deeper understanding of how each patient’s unique disease profile impacts therapy effectiveness. EGFR blockade can reverse chemotherapy resistance for some patients by downregulating apoptotic blockade and DNA repair caused by EGFR. Through the use of Cellworks personalized therapy biosimulation, we can pave the way for individualized decision making to determine which patients should be offered combination therapy upfront, thereby improving survival outcomes."

Study Design

Cellworks computational biosimulation was performed in this study to evaluate the additive value of chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations. A real-world retrospective cohort of 116 frontline NSCLC patients treated with osimertinib were obtained from the nationwide (US based) de-identified Flatiron Health-Foundation Medicine NSCLC clinico-genomic database (FH-FMI-CGDB). Biosimulated efficacy scores were generated for both osimertinib alone and in combination with carboplatin and pemetrexed. The study then analyzed chemotherapy-driven improvements in predicted clinical response, using the upper 95% confidence interval of the osimertinib ES as a threshold.

Study Results

The efficacy scores for osimertinib were significantly associated with clinical outcomes, confirming the predictive power of Cellworks computational biosimulation. Importantly, the biosimulated addition of chemotherapy to osimertinib led to a higher efficacy score for some patients, allowing for a more refined selection of patients, moving beyond the generalized conclusion that chemotherapy is beneficial in combination, which may apply to some, but not all, patients. The benefit of chemotherapy is unevenly distributed in the population, and biosimulation aids in the selection of which patients are most likely to get a benefit from combination compared to sequential treatment.

On September 9, 2024 Vir Biotechnology, Inc. (Nasdaq: VIR) reported that the exclusive worldwide license agreement with Sanofi announced on August 1, 2024, has closed following expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 (Press release, Sanofi, SEP 9, 2024, View Source [SID1234646457]). The agreement provides Vir with an exclusive worldwide license to three clinical-stage masked T-cell engagers (TCEs) with potential applications in a range of cancers and exclusive use of the proprietary PRO-XTENTM masking platform for oncology and infectious disease. Key employees from Sanofi with extensive scientific and development expertise in TCEs, and in-depth experience using the PRO-XTEN platform, will join Vir. Further information about the TCEs and their respective development plans will be provided at Vir’s upcoming R&D Day in November.

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"The closing of this strategic agreement with Sanofi is a pivotal moment for Vir and a significant opportunity to help address patient unmet needs. We are excited to further advance the masked T-cell engagers in clinical development, bolstering our clinical pipeline and adding near-term value creation opportunities," said Marianne De Backer, M.Sc., Ph.D., MBA, Vir’s Chief Executive Officer. "Our proven expertise in antibody engineering and clinical development combined with the innovative PRO-XTEN masking platform offers a unique opportunity to discover and develop therapies in oncology and infectious disease."

The clinical-stage assets Vir is licensing under the agreement are:

SAR446309 is a dual-masked HER2-targeted TCE in phase 1 clinical study including participants with metastatic treatment resistant HER2+ tumors such as breast and colorectal cancers.
SAR446329 is a dual-masked PSMA-targeted TCE in phase 1 clinical study including participants with metastatic castration-resistant prostate cancer.
SAR446368 is a dual-masked EGFR targeted TCE with an active IND. A phase 1 clinical study, which is expected to begin enrollment in the first quarter of 2025, will include participants with EGFR-expressing tumors of various types.
About the PRO-XTENTM Masking Platform

The PRO-XTEN proprietary masking platform can be applied to TCEs, cytokines, and other molecules potentially broadening the therapeutic index (TI) for patients. This technology exploits the high protease activity of the tumor microenvironment (TME) to specifically activate (unmask) drug candidates in tumor tissues. The selective cleavage results in the active molecule being released preferentially in the TME, potentially increasing the TI by minimizing off-target activity and toxicity associated with the systemic immune activation seen with traditional TCEs. Vir has exclusively licensed the PRO-XTEN proprietary masking platform from Sanofi in the fields of oncology and infectious diseases.