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.

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 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 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 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing novel solutions that treat urothelial and specialty cancers, reported results from a long-term follow-up study with JELMYTO (mitomycin) for pyelocalyceal solution, which is FDA approved for the treatment of low-grade, upper tract urothelial cancer (LG-UTUC) in adult patients (Press release, UroGen Pharma, FEB 12, 2025, View Source [SID1234650214]). Among patients from the OLYMPUS trial who achieved a complete response after primary chemoablation with JELMYTO (n=41, 20 of whom entered the long-term follow-up study), the median duration of response was 47.8 months (median follow-up 28.1 months [95% CI 13.1, 57.5]). The study results are published in the March issue of The Journal of Urology.

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"These results provide compelling evidence of the durability of JELMYTO in treating low-grade upper tract urothelial cancer," said Phillip Pierorazio, M.D., Chief, Section of Urology, Penn Presbyterian Medical Center, Professor of Surgery, Hospital of the University of Pennsylvania in Philadelphia, P.A. "The median duration of response of nearly four years in patients who achieved a complete response underscores the potential of JELMYTO to offer sustained control of the disease. These data reinforce the value of JELMYTO as an important treatment option for patients with LG-UTUC."

Of the 71 patients enrolled in OLYMPUS, 41 achieved a complete response after treatment with JELMYTO and had a median duration of response of 47.8 months (95% CI 13.0, not estimable), with median follow-up of 28.1 months (95% CI 13.1, 57.5).

"Prior research has emphasized that the main treatment objectives for LG-UTUC should focus on preventing relapse and preserving organ function, given the low likelihood of disease progression," said Mark Schoenberg, M.D., Chief Medical Officer of UroGen. "We are pleased with the study’s results, which offer strong evidence supporting the long-term effectiveness of JELMYTO as a primary treatment for LG-UTUC, with increasing data showing extended response duration."

The analysis has certain limitations, including its post-hoc nature and the inherent selection bias of the 20 patients enrolled in the long-term follow-up study.

To further explore the potential of JELMYTO in treating patients with LG-UTUC, investigators are currently enrolling participants in the JELMYTO uTRACT Registry to gather longitudinal real-world usage data. As of January 27, 2025, 21 sites have been activated with 228 patients enrolled.

About JELMYTO

JELMYTO (mitomycin) for pyelocalyceal solution is a mitomycin-containing reverse thermal gel containing 4 mg mitomycin per mL gel approved for the treatment of adult patients with low-grade-UTUC (LG-UTUC). JELMYTO is a viscous liquid when cooled and becomes a semi-solid gel at body temperature. The drug slowly dissolves over four to six hours after instillation and is removed from the urinary tract by normal urine flow and voiding. It is approved for administration in a retrograde manner via ureteral catheter or antegrade through a nephrostomy tube. The delivery system allows the initial liquid to coat and conform to the upper urinary tract anatomy. The eventual semisolid gel allows for chemoablative therapy to remain in the collecting system for four to six hours without immediately being diluted or washed away by urine flow.

About Upper Tract Urothelial Cancer (UTUC)

Urothelial cancer is the ninth most common cancer globally and the eighth most lethal neoplasm in men in the U.S. Between five percent and ten percent of primary urothelial cancers originate in the ureter or renal pelvis and are collectively referred to as UTUC. In the U.S., there are approximately 6,000 – 7,000 new or recurrent LG-UTUC patients annually. Most cases are diagnosed in patients over 70 years old, and these older patients often have multiple comorbidities. There are limited treatment options for UTUC, with the most common being endoscopic surgery or nephroureterectomy (removal of the entire kidney and ureter). Treatment with endoscopic surgery can be associated with a high rate of recurrence and relapse.