On April 27, 2025 Abbisko Therapeutics Co., Ltd. (Abbisko Therapeutics 02256.HK) reported that it has presented four late-breaking pre-clinical research posters at the 2025 AACR (Free AACR Whitepaper) conference held in Chicago, Illinois (USA) from April 25 to April 30 (Press release, Abbisko Therapeutics, APR 27, 2025, View Source;abbisko-therapeutics-presents-late-breaking-pre-clinical-research-results-on-absk112-egfr-exon20ins-absk131-prmt5mta-and-abk-kras-1-302439218.html [SID1234652204]). Results were shared for ABSK112 (EGFR exon20ins inhibitor), ABSK131 (PRMT5*MTA inhibitor), and ABK-KRAS-1 (pan-KRAS inhibitor), as well as results from a study investigating potential resistance mechanisms to KRAS G12C inhibitors.

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Abbisko presented the following posters at the 2025 AACR (Free AACR Whitepaper):

Title1: Preclinical Evaluation of ABSK112, a Selective and CNS-penetrant Compound with Strong HER2 Inhibitory Activity for Treating HER2-Driven Solid Tumors

Session Category: Late-Breaking Research: Experimental and Molecular Therapeutics 2

Session Date and Time: April 28, 2025, 2:00 PM – 5:00 PM (CDT)

Location: Poster Section 54

Poster Board Number: 14

Poster Number: LB240

Conclusion:

Our findings establish ABSK112 as a potent, selective and CNS-penetrant HER2 inhibitor, warranting further clinical evaluation of it as a monotherapy or in combination with HER2-targeted ADCs for the treatment of HER2+ cancers with brain metastases.

Title 2: Loss-of-Function (LoF) of KEAP1 promotes cell survival through multiple mechanisms, leading to resistance to KRAS G12C inhibitors

Session Title: Late-Breaking Research: Experimental and Molecular Therapeutics 3

Session Date and Time: April 29, 2025 9: 00AM – 12: 00 PM (CDT)

Location: Poster Section 52

Poster Board Number: 1

Poster Number: LB278

Conclusion:

KEAP1 LoF mutant NSCLCs develop resistance to KRAS G12C inhibitors through reduced drug-induced ROS accumulation, metabolic adaptation, and sustained activation of MAPK and AKT signaling. Combination therapies targeting glutamine metabolism (e.g., GLS1 inhibitors), MAPK (e.g., MEK inhibitors), and PI3K-AKT-mTOR pathways (e.g., BEZ235) reverse resistance and improve therapeutic efficacy in KEAP1-mutant cell lines. These strategies may restore sensitivity to KRAS G12C inhibitors and enhance clinical outcomes.

Title 3: The MTA-Cooperative PRMT5 Inhibitor ABSK131 Exhibits Potent Activity and Broad Synergistic Potential in MTAP-Deleted Cancer Models

Session Category: Late-Breaking Research: Experimental and Molecular Therapeutics 4

Session Date and Time: April 30, 2025 9:00 AM – 12:00 PM (CDT)

Location: Poster Section 51

Poster Board Number: 9

Poster Number: LB427

Conclusion:

ABSK131 exhibits strong anti-tumor activity in MTAP-deleted lung and pancreatic cancer models and synergizes effectively with multiple therapeutic agents. These findings support the continued clinical development of ABSK131 as both a monotherapy and in combination regimens for MTAP-deleted cancers.

Title 4: Discovery and characterization of a highly potent and orally available small-molecule inhibitor for diverse KRAS mutations

Session Category: Late-Breaking Research: Experimental and Molecular Therapeutics 4

Session Date and Time: April 30, 2025 9:00 AM – 12:00 PM (CDT)

Location: Poster Section 51

Poster Board Number: 13

Poster Number: LB431

Conclusion:

Taken together, ABK-KRAS-1 exhibits broad in vitro activity against different KRAS mutations and induces dose-dependent tumor regression in KRAS mutated xenograft models. Moreover, ABK-KRAS-1 possesses favorable drug-like properties. Here, ABK-KRAS-1 is presented as a promising therapeutic candidate for the treatment of cancers harboring KRAS mutations.

On April 27, 2025 Merck KGaA ("Merck") reported and confirms late-stage discussions with SpringWorks Therapeutics, Inc. on a potential acquisition (Press release, Merck KGaA, APR 27, 2025, View Source [SID1234652203]). The parties are in discussion on the basis of a price of around $47 per share.

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Merck notes that no final decision has been taken and no legally binding agreement has been entered into.

On April 27, 2025 Oncoinvent ASA, a clinical-stage radiopharmaceutical company developing innovative treatments for solid cancers, reported the 18-month follow-up results from its Phase 1 clinical trial (RAD-18-001) evaluating Radspherin in patients with platinum-sensitive recurrent ovarian cancer and peritoneal carcinomatosis (Press release, Oncoinvent, APR 27, 2025, https://www.oncoinvent.com/press-release/oncoinvent-reports-updated-18-month-data-from-phase-1-ovarian-cancer-trial-with-radspherin-no-new-recurrences-demonstrate-continued-promise-of-preventing-disease-progression/?utm_source=mailpoet&utm_medium=email&utm_source_platform=mailpoet [SID1234652202]). The trial was closed for recruitment at the end of 2023 and patients are currently in long-term follow-up.

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In this trial, 10 patients received a single intraperitoneal dose of 7 MBq Radspherin. Oncoinvent reported 12-month data in November 2024, where only 1 out of the 10 receiving the selected dose had peritoneal recurrence. At the 18-month follow-up, no further patient had experienced recurrence. i.e., only 10% of patients treated have so far had a recurrence. In similar populations, receiving best standard of care, it is expected that approximately 40% of patients would have had disease recurrence at this time point , , .

"Ovarian cancer’s characteristic peritoneal metastasis lead to frequent recurrences despite a comprehensive treatment approach," commented Dr. Luis Chiva, Principal Investigator and Director of Department of Obstetrics and Gynecology, Clinica Universidad de Navarra, Spain. "I am proud to be part of a study program exploring whether Radspherin may become a novel therapy that can prevent disease progression, offering hope for a better and longer life for my patients."

"These compelling results underscore Radspherin’s potential to significantly reduce peritoneal recurrence in ovarian cancer patients," said Øystein Soug, CEO of Oncoinvent. "The data not only reinforce our confidence in Radspherin but also support its advancement in Phase 2 trials, including the ongoing randomized controlled Phase 2 trial assessing progression-free survival in patients with peritoneal metastasis from ovarian cancer."

To discuss these promising clinical results, provide an update on operations, and discuss the ongoing Phase 2 trial, Oncoinvent has decided to move up its Quarterly Update from the previously announced May 27 to April 30 at 11:00 CEST.

On April 27, 2025 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics ("Molecular Partners" or the "Company"), reported the presentation of three posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025, taking place April 25–30 in Chicago, IL (Press release, Molecular Partners, APR 27, 2025, View Source [SID1234652200]). The first poster includes positive Investigational New Drug (IND)-enabling data for MP0712, a Radio-DARPin targeting DLL3 and labeled with 212Pb for small cell lung cancer patients. The second poster presents initial preclinical data on the second 212Pb-based Radio-DARPin, targeting mesothelin (MSLN) in solid tumors – both programs are co-developed with Orano Med. The third poster includes additional preclinical proof-of-concept data on the logic-gated CD3 Switch-DARPin T cell engager with CD2 co-stimulation in solid tumors.

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"Our presentations at AACR (Free AACR Whitepaper) highlight the breadth of Molecular Partners’ DARPin innovation and the progress in our strategic Radio-DARPin partnership with Orano Med. Our first Radio-DARPin program, MP0712, targeting DLL3, is well advanced and on track to provide initial clinical data in the second half of 2025. Additionally, we are proud to present the first preclinical data from our second program with Orano Med, targeting MSLN. The results show substantial uptake into MSLN-positive tumors, with limited accumulation in other organs, justifying continued investment in our RDT x MSLN program for solid tumors," said Patrick Amstutz, Ph.D., CEO of Molecular Partners.

"Furthermore, we continue to advance our wholly-owned logic-gated and co-stimulated T cell engager program. Our SWITCH approach activates CD3/T-cells only when binding to tumor-associated antigens, while remaining inactive in circulation. This gating allows us to add a CD2 DARPin for co-stimulation without the risk of fratricide. This project demonstrates the value of our platform, which can be used for any target combination."

Preclinical data presented on MP0712, a DLL3-targeting and 212Pb-labeled Radio-DARPin, show a high tumor uptake and a favorable safety profile for MP0712, with good efficacy and tumor reduction in mouse models matching clinically relevant DLL3 expression levels. With these data, the IND-enabling package is complete; IND filing and initial first-in-human clinical data are expected in 2025. DLL3 is a promising target for radioligand therapy as it is highly upregulated in small cell lung cancer and other high-grade neuroendocrine tumors, while not expressed in healthy tissues.

The MSLN x 212Pb Radio-DARPin poster outlines how MSLN may be a promising target for ovarian cancer due to its differentiated expression profiles – high in tumor, and lower in healthy tissues. High levels of shed MSLN, however, can act as a decoy receptor and have historically hampered the development of MSLN-targeted therapeutics. Molecular Partners has leveraged the unique properties of DARPins to develop a Radio-DARPin able to selectively bind membrane-bound MSLN without being impacted by shed MSLN. In vivo results show a favorable biodistribution with strong tumor accumulation of the Radio-DARPin in a MSLN-overexpressing model in mice.

Preclinical proof-of-concept data on Molecular Partners’ conditionally activated CD3 Switch-DARPin shows it activates T cells specifically in the presence of cells co-expressing MSLN and epithelial cell adhesion molecule (EpCAM), increasing tumor specificity. Concurrent CD2 co-engagement leads to sustained T cell activation and cytotoxic capacity, preventing T cell dysfunction. The Switch-DARPin effectively induces significant tumor regression in mice engrafted subcutaneously with MSLN- and EpCAM-expressing cells, without signs of T cell activation in the periphery, indicating a favorable safety profile.

Click here to access the poster presentations, which will be made available on Molecular Partners’ website.

Details of the presentations:

MP0712, the first anti-DLL3 212Pb Radio-DARPin (RDT) candidate for targeted radiotherapy of small cell lung cancer (SCLC)
Session Category: Experimental and Molecular Therapeutics
Session Title: Biochemical Modulators of Cancer / Differentiation Therapeutic Strategies
Session Timing: Sunday April 27 at 2:00pm – 5:00pm CST
Location: Poster Section 16, Poster Board Number: 13
Published Abstract Number: 346

Development of 212Pb-based Radio-DARPin therapy (RDT) for the treatment of mesothelin (MSLN)-positive solid tumors
Session Category: Experimental and Molecular Therapeutics
Session Title: Biochemical Modulators of Cancer / Differentiation Therapeutic Strategies
Session Timing: Sunday April 27 at 2:00 – 5:00pm CST
Location: Poster Section 16, Poster Board Number: 6
Published Abstract Number: 339

Next-generation multi-specific and conditionally activated CD3 Switch-DARPins with CD2 co-stimulation to tackle the current limitations of T cell engagers in solid tumors
Session Category: Experimental and Molecular Therapeutics
Session Title: Therapeutic Approaches to Attack the Tumor Microenvironment
Session Timing: Monday April 28 at 2:00pm – 5:00pm CST
Location: Poster Section 24, Poster Board Number: 3
Published Abstract Number: 3119

On April 27, 2025 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing novel solutions that treat urothelial and specialty cancers, reported a duration of response of nearly four years 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, APR 27, 2025, View Source [SID1234652198]).

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Among patients from the OLYMPUS trial who achieved a complete response after primary chemoablation with JELMYTO (n=41), the median duration of response was 47.8 months, irrespective of whether their cancer was new-onset or recurrent (median follow-up 28.1 months [95% CI 13.1, 57.5]). Of these patients, 21 had new-onset UTUC, and 20 had recurrent UTUC at baseline; there were no significant differences in durability between groups, with 8 patients in each group experiencing recurrence or death not due to treatment. Twenty patients entered long-term follow-up with a median follow-up of 53.3 months (95% CI 27.9, 65.3); median duration of response was not estimable (95% CI 43.5, not estimable) due to the low event rate.

"This sub-analysis highlights new evidence for the impressive long-term benefits of JELMYTO, in both new-onset and recurrent low-grade upper tract urothelial cancer patients," said Brian Hu, MD, Associate Professor of Urology at Loma Linda University Health, CA. "These findings further establish JELMYTO as an effective treatment, providing patients with durable responses and a significant reduction in recurrence rates."

LG-UTUC is a challenging disease often managed through endoscopically guided ablation, but recurrence is common, and patients face a lifetime of surveillance and potential complications. The OLYMPUS Phase 3 trial evaluated JELMYTO, a reverse thermal gel containing mitomycin (4 mg/mL), as a primary treatment for adults with LG-UTUC. While the overall trial demonstrated the potential of JELMYTO to significantly eradicate disease, this sub-analysis focuses specifically on patients with new-onset and recurrent LG-UTUC who achieved a complete response, providing new insights into the durability and long-term effectiveness of the treatment. Limitations of this study include the post-hoc nature of the analysis and potential selection bias regarding entry of patients into long-term follow-up.

"We are encouraged by the long-term outcomes evidence observed in both new-onset and recurrent LG-UTUC patients," said Mark Schoenberg, MD, Chief Medical Officer, UroGen. "The sub-analysis provides further compelling evidence that JELMYTO offers durable disease control and clinically meaningful responses, which could significantly reduce the need for repeated interventions. We look forward to expanding our understanding of JELMYTO through the ongoing uTRACT Registry and further evaluating its potential in real-world settings."

To further explore the potential of JELMYTO in treating patients with LG-UTUC, investigators are currently enrolling participants in the JELMYTO uTRACT Registry (NCT05874921) to gather longitudinal real-world usage data. As of April 2025, 22 sites have been activated with 251 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 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

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.