On February 12, 2025 AbbVie (NYSE: ABBV) and Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, reported a collaboration and option-to-license agreement to develop novel tumor-activated, antibody-based immunotherapies, including masked T-cell engagers, leveraging Xilio’s proprietary technology (Press release, Xilio Therapeutics, FEB 12, 2025, View Source [SID1234650215]).

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Xilio has developed a proprietary, clinically-validated platform technology for tumor-activated biologics. The company is advancing a pipeline of novel, clinical and pre-clinical immunotherapies, including masked multispecific molecules, designed to achieve tumor-selective activation by leveraging masking and other unique components that are optimized for the specific target. This allows focused activity within the tumor microenvironment with the goal of minimizing systemic adverse events.

"AbbVie is committed to expanding our R&D efforts in oncology. This includes investigation of novel immunotherapy approaches that aim to generate improved next-generation cancer treatments for patients in need," said Theodora S. Ross, M.D., Ph.D., vice president, early oncology research and development, AbbVie. "This partnership with the Xilio team, further exemplifies our commitment."

"This collaboration with AbbVie, a global leader in developing and commercializing oncology therapies, allows us to accelerate the expansion of our technology to next-generation immunotherapies, including T-cell engagers," said Uli Bialucha, Ph.D., chief scientific officer of Xilio. "We look forward to working with the AbbVie team to apply our deep protein engineering expertise coupled with tumor-selective activation through our novel formats for masked T-cell engagers."

Under the terms of the agreement, Xilio will receive $52.0 million in total upfront payments, including a $10.0M equity investment, and will be eligible to receive up to approximately $2.1 billion in total contingent payments for option-related fees and milestones plus tiered royalties.

Xilio Investor Conference Call Information

Xilio will host a conference call and webcast today at 8:30 am EST. Viewers can access the webcast by using this link. Listeners who require dial-in access should register here to receive a unique PIN and information to join the call. Listeners are encouraged to join at least 15 minutes prior to the scheduled start time. The webcast will also be accessible under "Events & Presentations" in the Investors & Media section of the Xilio Therapeutics website at View Source A replay of the webcast will be archived on the website for 30 days following the presentation.

On February 12, 2025 Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology, reported that BOT/BAL will be featured in two presentations at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) IO Annual Meeting that will take place on February 23-26 in Los Angeles, California (Press release, Agenus, FEB 12, 2025, View Source [SID1234650218]). An oral presentation will highlight interim data from the ongoing Phase 2 study of botensilimab and balstilimab (BOT/BAL) in combination with MiNK Therapeutics’ iNKT cell therapy, AgenT-797, in patients with refractory (2L+) gastric cancer (NCT06251973). A Trial-in-Progress (TiP) poster will feature data from the ongoing Phase 1/2 study of BOT/BAL in first-line MSS colorectal cancer (NCT05627635).

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Presentation Details:

Abstract Title: First-line botensilimab and balstilimab optimization in microsatellite stable colorectal cancer (MSS-CRC) without liver metastasis (BBOpCo)

Session : Poster Session A

Session Date and Time: Monday, February 24th , 1:45-4:45 p.m. PST

Abstract Title: Biomarker analysis from phase 2 study of AgenT-797 (invariant natural killer T-cells), botensilimab (a Fc-enhanced CTLA-4 Inhibitor) with balstilimab (anti-PD-1) in PD-1 refractory gastroesophageal cancer (GEC)

Session : Proffered Papers, Session 2

Session Date and Time: Tuesday, February 25th , 1:00-1:45 p.m. PST

On February 12, 2025 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd （"Kelun-Biotech" reported that it will present efficacy and safety results from the Phase 1/2 KL264-01/MK-2870-001 study (NCT04152499) of its anti-TROP2 ADC sacituzumab tirumotecan (sac-TMT, formerly SKB-264/MK-2870) as monotherapy in patients with unresectable, locally advanced or metastatic urothelial carcinoma (UC) who progressed on or after prior anti-cancer therapies at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (GU) Cancers Symposium 2025, to be held in San Francisco, USA, from Feb. 13-15, 2025 (Press release, Kelun, FEB 12, 2025, View Source [SID1234650219]).These findings will be presented in a poster session on February 14, 2025, local time (Abstract #796).

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The abstract for the above study was also published on the official website of the ASCO (Free ASCO Whitepaper) GU Cancers Symposium 2025 on February 10, 2025, local time.

UC

Eligible participants had histologically/cytologically confirmed locally advanced or metastatic UC, had experienced progression of disease on ≥1 prior line of platinum-based therapy and had received prior anti-PD-(L)1 therapy; platinum-ineligible patients were eligible if they received prior anti-PD-(L)1 therapy (prior neoadjuvant/adjuvant therapy counted as a line of therapy if patients progressed within 12 months). Patients had Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1 and measurable disease by CT/MRI. Patients received sac-TMT 5 mg/kg every two weeks (Q2W) until progression of disease, unacceptable toxicity or withdrawal of consent.

As of data cutoff on June 30, 2024, 49 treated patients had a minimum follow-up of ≥9 weeks. Eleven patients received sac-TMT as 2L treatment; 38 received sac-TMT as 3L+ treatment. Median age was 62 and 61 years old, respectively; most patients were Asian (82%; 100%). Median (range) follow-up was 9.5 (7.5-16.2) months and 11.7 (7.8-17.4) months, respectively. Among all patients, objective response rate (ORR) was 31%. Efficacy data are shown below:

Outcome

UC 2L

sac-TMT 5 mg/kg

(n=11)

UC 3L+

sac-TMT 5 mg/kg

(n=38)

Confirmed ORRa n (%)

5 (45)

10 (26)

95% CI

16.7-76.6

13.4-43.1

CR n (%)

1 (9)

0

PR n (%)

4 (36)

10 (26)

SD n (%)

3 (27)

17 (45)

PD n (%)

2 (18)

10 (26)

Not evaluable n (%)

1 (9)

1 (3)

Median DoRb, months (range)

NE (3.5+ to 13.9+)

NE (2.1 to 15.0+)

Median PFSb, months (95% CI)

5.8 (1.7-NE)

5.0 (3.5-7.4)

Median OSb, months (95% CI)

NE (2.0-NE)

11.5 (8.9-NE)

CI=Confidence interval, CR=Complete response, PR=Partial response, SD=Stable disease, PD=Progression of disease, DoR=Duration of response, PFS=Progression-free survival, OS=Overall survival, NE=Not evaluable.

"+" No progressive disease or death as of last disease assessment.

a Includes all patients as-treated.

b Kaplan-Meier method for censored data.

By safety data cutoff (May 21, 2024), grade ≥3 treatment-related adverse events (TRAEs) occurred in 59% of patients. The most common Grade 3-4 TRAEs were anemia (39%), neutrophil count decreased (29%), white blood cells count decreased (16%), stomatitis (12%), and platelet count decreased (8%), which were generally reversible with dose modifications and/or supportive care. No Grade 5 TRAEs occurred; TRAEs led to sac-TMT discontinuation in one patient.

About sac-TMT

Sac-TMT, a core product of the Company, is a novel human TROP2 ADC in which the Company has proprietary intellectual property rights, targeting advanced solid tumors such as NSCLC, breast cancer (BC), gastric cancer (GC), gynecological tumors, among others. Sac-TMT is developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor with a drug-to-antibody-ratio (DAR) of 7.4. Sac-TMT specifically recognizes TROP2 on the surface of tumor cells by recombinant anti-TROP2 humanized monoclonal antibodies, which is then endocytosed by tumor cells and releases KL610023 intracellularly. KL610023, as a topoisomerase I inhibitor, induces DNA damage to tumor cells, which in turn leads to cell-cycle arrest and apoptosis. In addition, it also releases KL610023 in the tumor microenvironment. Given that KL610023 is membrane permeable, it can enable a bystander effect, or in other words kill adjacent tumor cells.

Previously, the National Medical Products Administration (NMPA) has approved the marketing of sac-TMT in China for 2L+ advanced triple negative breast cancer (TNBC), and accepted two supplemental new drug applications (sNDA) seeking the approvals of sac-TMT monotherapy for 2L/3L EGFR-mutant non-small cell lung cancer (NSCLC).

In May 2022, the Company licensed the exclusive rights to MSD (the tradename of Merck & Co., Inc, Rahway, NJ, USA) to develop, use, manufacture and commercialize sac-TMT in all territories outside of Greater China (which includes Mainland China, Hong Kong, Macao and Taiwan).

On February 12, 2025 Bio-Path Holdings, Inc., (NASDAQ:BPTH), a biotechnology company leveraging its proprietary DNAbilize liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid cancer and obesity drugs, reported an update from the Company’s ongoing Phase 1/1b clinical trial evaluating BP1002 for the treatment of refractory/relapsed acute myeloid leukemia (AML), including venetoclax-resistant patients (Press release, Bio-Path Holdings, FEB 12, 2025, View Source [SID1234650242]). The Company announced a meaningful patient response to treatment and the clinical trial has progressed to the fourth, higher dose cohort of 90 mg/m2.

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"We were excited to learn that one patient in the third cohort had a meaningful response to just one treatment cycle, experiencing stable disease and a significant reduction in blast count, which we believe offers promise for venetoclax-resistant AML patients with limited treatment options," said Peter Nielsen, President and Chief Executive Officer of Bio-Path Holdings. "AML patients that fail or relapse from frontline venetoclax-based therapy have very poor prognosis with a median overall survival of less than three months. The third dosing cohort completed enrollment faster than expected, which we believe reflects the urgent need for additional treatment options. We look forward to quickly advancing this study through the fourth dosing cohort and into the combination therapy segment of this Phase 1/1b study with increased levels of BP1002 for the treatment of these vulnerable patients."

The current standard of care for patients with AML not eligible for intensive chemotherapy is venetoclax, an oral Bcl-2 inhibitor that targets the BH3 domain of the Bcl-2 protein, in combination with a hypomethylating agent or with low-dose cytarabine. However, many patients become resistant to venetoclax treatment. A published study found that AML patients who had relapsed from frontline venetoclax-based treatment were refractory to salvage therapy and had a median survival of less than 3 months. By targeting Bcl-2 at the mRNA level rather than the protein, BP1002 may overcome and prevent some of the mechanisms of resistance that affect venetoclax treatment.

The Phase 1/1b clinical trial is being conducted at several leading cancer centers in the United States, including the Weill Medical College of Cornell University, The University of Texas MD Anderson Cancer Center, Scripps Health, and The University of California at Los Angeles Cancer Center. The approved treatment cycle is two doses per week over four weeks, resulting in eight doses administered over twenty-eight days. The Phase 1b portion of the study is expected to commence after completion of BP1002 monotherapy cohorts and will assess the safety and efficacy of BP1002 in combination with decitabine in refractory/relapsed AML patients.

Gail J. Roboz, M.D., is the National Principal Investigator for the Phase 1/1b trial. Dr. Roboz is a Professor of Medicine and Director of the Clinical and Translational Leukemia Program at the Weill Medical College of Cornell University and the New York-Presbyterian Hospital in New York City. Gary Schiller, M.D., The University of California at Los Angeles Cancer Center, Maro Ohanian, D.O., Department of Leukemia, University of Texas MD Anderson Cancer Center, and David Hermel, M.D., Scripps Health, are each serving as principal investigators.

On February 12, 2025 Akeso, Inc. (9926. HK) ("Akeso" or the "Company") reported the recent completion of the first patient enrollment in the Phase 3 randomized, double-blind, multicenter clinical trial (COMPASSION-30/AK104-309) for its independently developed PD-1/CTLA-4 bispecific antibody, cadonilimab (Press release, Akeso Biopharma, FEB 12, 2025, View Source [SID1234650220]). This study is evaluating the efficacy of cadonilimab compared to sugemalimab (PD-L1) as a consolidation therapy for patients with locally advanced, non-resectable, non-small cell lung cancer (NSCLC) who have not experienced disease progression following concurrent or sequential chemoradiotherapy.

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The COMPASSION-30/AK104-309 study is led by Prof. Jinming Yu, Academician of the Chinese Academy of Engineering and Director of the Oncology Hospital at Shandong First Medical University.

Currently, consolidation therapy with immune checkpoint inhibitors following concurrent or sequential chemoradiotherapy is the standard of care for patients with unresectable NSCLC. The use of immune checkpoint inhibitors as consolidation therapy has demonstrated a modest improvement in overall survival for patients. However, despite these advancements, there continues to be a significant unmet clinical need within this patient population, underscoring the urgent demand for more effective treatment options.

As a global first-in-class bispecific antibody targeting both PD-1 and CTLA-4, cadonilimab is anticipated to enhance the efficacy of immunotherapy compared to PD-1/PD-L1 single-target antibodies. Cadonilimab exerts its effects through multiple mechanisms that contribute to the "normalization" of the tumor microenvironment. Its unique tetravalent symmetric structure, combined with Fc modifications, facilitates targeted accumulation in tumor tissues. These distinctive features enable cadonilimab to potentially improve the effectiveness of cancer immunotherapy while minimizing the risk of adverse effects.

About Cadonilimab
Cadonilimab is a novel global first-in-class PD-1/CTLA-4 bi-specific immuno-therapy drug independently developed by Akeso. In June 2022, cadonilimab was granted marketing approval by the NMPA for the treatment of recurrent/metastatic cervical cancer patients who have progressed on or after platinum-based chemotherapy, and became the world’s first approved PD-1/CTLA-4 bi-specific antibody. In September 2024, cadonilimab as a first-line treatment of unresectable locally advanced, recurrent or metastatic G/GEJ adenocarcinoma was approved in China. Currently, the Company is conducting more than 23 clinical trials of cadonilimab combination therapies covering 16 indications including but not limited to cervical cancer, gastric cancer, liver cancer and lung cancer.