On February 20, 2025 ReCerise Therapeutics Inc. ("ReCerise"), a company committed to research and development of first-in-class therapeutics in oncology, reported to have entered into a research partnership with the National Cancer Centre Singapore ("NCCS") to develop innovative treatments utilizing multi-omics data analyses in hepatocellular carcinoma (HCC) (Press release, ReCerise Therapeutics, FEB 20, 2025, View Source [SID1234650438]).

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This collaboration will be conducted under the PLANet programme (Precision Medicine in Liver Cancer across an Asia-Pacific Network), which was conceptualized and led by NCCS based on the intra-tumoral heterogeneity of liver tumors and its highly dynamic tumor microenvironment (TME). The longitudinal study performs comprehensive multi-omics profiling of tumor and blood samples from liver cancer patients. This collaboration will leverage the processed multi-omics data collected under the PLANet programme, and will be led by Prof. Pierce Chow Kah Hoe, a prominent global expert in the field of HCC. Prof Chow is a Senior Consultant Surgeon in the Division of Surgery and Surgical Oncology at Singapore General Hospital (SGH) and NCCS, and principal investigator of the PLANet programme.

HCC is a highly prevalent cancer with a poor prognosis due to late diagnosis and low response to existing immunotherapeutic treatment options. ReCerise was established with the purpose of investigating and developing new therapeutic modalities to address such unmet medical needs. So far, basic research and proof-of-concept studies on a liver specific protein have demonstrated promise as a potential solution. ReCerise hopes to expand upon this background knowledge by utilizing real-life evidence in collaboration with NCCS to investigate an HCC patient cohort and confirm the target’s expression and its effect on the liver microenvironment.

"We are excited to collaborate with NCCS to accelerate the development of an innovative new drug for the treatment of liver cancer that ReCerise has been working toward," said Yong-Bae Kim, CEO of ReCerise Therapeutics. "Through this joint research, we plan to conduct multi-faceted studies on the development potential of RCT1213, a hepatocellular carcinoma treatment candidate currently under development, by utilizing the various omics data and research database of Asian HCC patients at NCCS."

The research collaboration between these two parties is a research and development project funded by the Korean government and is subject to the management and supervision of the Korea Evaluation Institute of Industrial Technology (KEIT).

On February 20, 2025 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported expansion of its oncology pipeline portfolio through the acquisition of assets relating to a next-generation oncolytic virus ICVB-1042 from IconOVir Bio, Inc. (IconOVir) (Press release, UroGen Pharma, FEB 20, 2025, View Source [SID1234650421]). In addition, UroGen also announced that it has entered into multiple strategic research collaborations to explore the potential of its proprietary RTGel technology to enhance clinical effectiveness of multiple immunotherapies, including optimizing dwell time to improve treatment outcomes.

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"UroGen’s long-term growth strategy is built on advancing our uro-oncology pipeline, expanding our portfolio, and driving innovation in cancer treatment," said Liz Barrett, President and Chief Executive Officer of UroGen. "The acquisition of ICVB-1042, a next-generation investigational oncolytic virus, marks a significant milestone in our plan to develop novel, locally administered therapies for bladder cancer and other specialty cancers. This strategic investment underscores our commitment to identifying and advancing high-impact therapies that address critical unmet needs. Through targeted acquisitions and research collaborations, we are strengthening UroGen’s leadership in oncology and laying the foundation for sustained innovation and growth."

The use of biological agents to treat bladder cancer has its roots in the development of Bacillus Calmette-Guérin (BCG) therapy. Much like BCG therapy, ICVB-1042 is being developed to activate the immune system within the tumor microenvironment, but unlike BCG therapy, ICVB-1042 has the potential to selectively destroy cancer cells while retaining potency and trigger a robust immune response. A fusion of potency and cancer cell destruction would mark a groundbreaking step forward, unlocking new possibilities in the fight against cancer.

"The treatment of bladder cancer has long been shaped by immunological approaches such as BCG therapy. UroGen now seeks to advance bladder cancer treatment with highly targeted, next-generation viral immunotherapies like ICVB-1042," said Mark Schoenberg, M.D., Chief Medical Officer of UroGen. "ICVB-1042 may represent an exciting leap forward, with several attributes we believe differentiate this asset from other oncolytic viruses. Supported by a robust non-clinical data package, we are eager to develop this investigational therapy as a potential new treatment in localized cancer."

Asset Purchase

On February 14, 2025, UroGen acquired certain assets of IconOVir, including product candidate ICVB-1042, and assumed certain liabilities and obligations of IconOVir arising under certain acquired contracts. As consideration for the assets, UroGen issued IconOVir 374,843 of its ordinary shares (representing a value of approximately $4.0 million based on 30-day VWAP), agreed to pay IconOVir a one-time payment of $15.0 million in cash upon the achievement of a cumulative aggregate worldwide net sales milestone for all products, including combination products, that incorporate or comprise ICVB-1042 (ICVB Products), and agreed to pay IconOVir a certain low, single-digit percentage royalty on a ICVB Product-by-ICVB Product basis on annual worldwide net sales of such ICVB Product.

Conference Call & Webcast Information

Members of UroGen’s management team will host a live conference call and webcast today at 12:00 PM ET to discuss the Company’s long-term growth strategy. The live webcast can be accessed by visiting the Investors section of the Company’s website at View Source Please connect at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast.

On February 20, 2025 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, reported multiple oral and poster presentations, including an oral presentation of additional analyses from the ongoing Phase 2 RAMP 201 (ENGOT-ov60/GOG-3052) trial evaluating the investigational combination of avutometinib plus defactinib in patients with recurrent low-grade serous ovarian cancer (LGSOC), at the Society of Gynecologic Oncology (SGO) 2025 Annual Meeting on Women’s Cancer, to be held on March 14-17 in Seattle, Washington (Press release, Verastem, FEB 20, 2025, View Source [SID1234650424]). Verastem will also have an exhibition booth (#622) at the meeting where it will be available to discuss its ongoing cancer research.

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"The presentation of the RAMP 201 primary analysis, which served as the basis of the acceptance of our NDA that is under Priority Review with the FDA, includes additional subgroup analysis by KRAS mutational status," said Dan Paterson, president, and chief executive officer of Verastem Oncology. "We look forward to sharing these learnings with many of the world’s leading gynecologic oncologists at SGO as part of our continued commitment to people living with recurrent low-grade serous ovarian cancer. We also recognize the importance of these findings to the broader cancer community as part of our growing pool of data reinforcing the potential to change expectations in managing RAS/MAPK pathway-driven cancers."

Oral Presentation:

Abstract Title: Avutometinib + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer (ENGOT-ov60/GOG-3052/RAMP 201): Dose Intensity and Subgroup Analysis
Presenter: Rachel Grisham, M.D.
Session: Focused Forum XV: Ongoing IMPACT
Date/Time: Monday, March 17, 2025, 9:15 am PST
Oral Presentation​ – Investigator-Sponsored Trial:

Abstract Title: A Phase II Study of Avutometinib and Defactinib in Advanced or Recurrent Gynecologic Mesonephric Cancer: Interim Results
Presenter: Rachel Grisham, M.D.
Session: Focused Forum IV: Finding IMPACT: The Needle in the Haystack​
Date and Time: Saturday, March 15, 2025, 4:15 pm PST
Preclinical Virtual Poster​:

Abstract Title: Preclinical Efficacy of the Estrogen Receptor Degrader Fulvestrant in Combination with RAF/MEK clamp Avutometinib and FAK Inhibitor in Low-Grade Serous Ovarian Cancer with Acquired Resistance to Chemotherapy and Aromatase Inhibitor
Study Author: Cem Demirkiran, M.D.
About the Avutometinib and Defactinib ​​Combination

Avutometinib is an oral RAF/MEK clamp that potently inhibits MEK1/2 kinase activities and induces inactive complexes of MEK with ARAF, BRAF, and CRAF, potentially creating a more complete and durable anti-tumor response through maximal RAS/MAPK pathway inhibition. In contrast to currently available MEK-only inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of the MEK-only inhibitors.

Defactinib is an oral, selective inhibitor of focal adhesion kinase (FAK) and proline-rich tyrosine kinase-2 (Pyk2), the two members of the focal adhesion kinase family of non-receptor protein tyrosine kinases. FAK and Pyk2 integrate signals from integrin and growth factor receptors to regulate cell proliferation, survival, migration, and invasion. FAK activation has been shown to mediate resistance to multiple anti-cancer agents, including RAF and MEK inhibitors.

Verastem Oncology is currently conducting clinical trials with avutometinib with and without defactinib in RAS/MAPK-driven tumors as part of its Raf And Mek Program or RAMP. Verastem is currently enrolling patients and activating sites for RAMP 301 (GOG-3097/ENGOT-ov81/NCRI) (NCT06072781), an international Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent low-grade serous ovarian cancer (LGSOC).

Verastem was granted Priority Review and a Prescription Drug User Fee Act (PDUFA) date of June 30, 2025, for its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA), for the investigational combination of avutometinib and defactinib in adults with recurrent KRAS mutant LGSOC who received at least one prior systemic therapy. Verastem initiated a rolling NDA in May 2024 to the FDA and completed its NDA submission in October 2024. The FDA granted Breakthrough Therapy Designation for the treatment of patients with recurrent LGSOC after one or more prior lines of therapy, including platinum-based chemotherapy, in May 2021. Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by the FDA for the treatment of LGSOC.

Verastem Oncology has established a clinical collaboration with Amgen to evaluate LUMAKRAS (sotorasib) in combination with avutometinib and defactinib in both treatment-naïve patients and in patients whose KRAS G12C mutant non-small cell lung cancer progressed on a G12C inhibitor as part of the RAMP 203 trial (NCT05074810). Verastem has received Fast Track Designation from the FDA for the triplet combination in April 2024. RAMP 205 (NCT05669482), a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer, is supported by the PanCAN Therapeutic Accelerator Award. FDA granted Orphan Drug Designation to the avutometinib and defactinib combination for the treatment of pancreatic cancer.

On February 20, 2025 FibroGen, Inc. (NASDAQ: FGEN) reported the sale of its China subsidiary to AstraZeneca for approximately $160 million (Press release, FibroGen, FEB 20, 2025, View Source [SID1234650405]).

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"Today, we announced the sale of FibroGen China to AstraZeneca, our long-time strategic partner for roxadustat in China, bolstering our company on several fronts. It strengthens our financial position, meaningfully extending our cash runway into 2027, and enables us to continue progressing the clinical development program for FG-3246, our first-in-class, CD46 targeting antibody drug conjugate, and FG-3180, our companion PET imaging agent, in mCRPC," said Thane Wettig, Chief Executive Officer of FibroGen. "After a thorough evaluation of alternatives, we believe selling our China operations and repaying our term loan is in the best interest of FibroGen’s stakeholders. We are grateful for our China colleagues, and in particular Christine Chung, our Head of China Operations, for their unwavering commitment to patients and successful commercialization of roxadustat in China. Now, we turn the page to the next exciting chapter for FibroGen."

Under the terms of the agreement, FibroGen will receive an enterprise value of $85 million plus FibroGen net cash held in China at closing, currently estimated to be approximately $75 million, totaling approximately $160 million. The transaction is expected to close by mid-2025, pending customary closing conditions, including regulatory review in China. Following the close of the transaction, FibroGen will repay its term loan facility to investment funds managed by Morgan Stanley Tactical Value, further simplifying the Company’s capital structure. The combined transactions are expected to extend the Company’s cash runway into 2027.

Upon closing, AstraZeneca will obtain all rights to roxadustat in China. Roxadustat is the category leader in brand value share for the treatment of anemia in chronic kidney disease with a pending regulatory decision for chemotherapy-induced anemia.

FibroGen maintains its rights to roxadustat in the U.S. and in all markets not licensed to Astellas. The Company continues to evaluate a development plan for roxadustat in anemia associated with lower-risk myelodysplastic syndrome (LR-MDS), a high-value indication with significant unmet medical need. The Company is planning for an FDA meeting in the second quarter of 2025 to determine the potential next steps for the development program for roxadustat in the U.S.

In addition, FibroGen continues to advance the clinical development of its lead asset, FG-3246, and its companion PET imaging agent, FG-3180, with the initiation of the Phase 2 monotherapy trial of FG-3246 in patients with mCRPC expected in the second quarter of 2025.

BofA Securities, Inc. is acting as exclusive financial advisor and Ropes & Gray LLP is acting as legal advisor to FibroGen on this transaction.

Conference Call and Webcast Presentation
FibroGen management team will host a conference call and webcast presentation today, February 20, 2025 at 8:30 a.m. ET to discuss the sale of FibroGen China. A live Q&A session will follow the brief presentation. Interested parties may access a live audio webcast of the conference call here. To access the call by phone, please register here, and you will be provided with dial in details. A replay of the webcast will also be available for a limited time on the Events & Presentations page on FibroGen’s website.

On February 20, 2025 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing the tuspetinib (TUS)-based triple drug frontline therapy to treat patients with newly diagnosed AML, reported that the Cohort Safety Review Committee (CSRC) monitoring Aptose’s Phase 1/2 TUSCANY trial of tuspetinib in combination with standard of care dosing of venetoclax and azacitidine (TUS+VEN+AZA triplet) has unanimously approved escalating from 40 mg TUS to 80 mg TUS based on its favorable review of data from the first four patients in the trial (Press release, Aptose Biosciences, FEB 20, 2025, View Source [SID1234650425]). The TUS+VEN+AZA triplet is being developed as a frontline therapy to treat large, mutationally diverse populations of newly diagnosed AML patients who are ineligible to receive induction chemotherapy.

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No significant safety concerns or dose limiting toxicities (DLTs) have been reported, including no prolonged myelosuppression of subjects in remission. All four subjects treated in the 40 mg cohort remain on study while enrollment is open for the 80 mg cohort.

"With a high level of enthusiasm, our CSRC – comprised of study investigators that include key leaders in the development of therapeutic agents for AML – recommended we escalate dosing in our TUSCANY trial with tuspetinib," said Rafael Bejar, M.D., Ph.D., Chief Medical Officer of Aptose. "The lack of prolonged myelosuppression with no DLT’s and several complete responses, including an MRD-negative CRh noted early in treatment, is truly encouraging. As one our chief investigators remarked, if the TUS+VEN+AZA triplet shows efficacy and tolerability in difficult-to-treat AML populations with little myelosuppression, tuspetinib could be a game changer for frontline AML treatment."

TUSCANY: TUS+VEN+AZA Triplet Phase 1/2 Study

Tuspetinib based TUS+VEN+AZA triplet therapy is being advanced in the TUSCANY Phase 1/2 trial with the goal of creating an improved frontline therapy for newly diagnosed AML patients that is active across diverse AML populations, durable, and well tolerated. Earlier APTIVATE trials of TUS as a single agent and in combination as TUS+VEN demonstrated favorable safety and broad activity in diverse relapsed or refractory (R/R) AML populations that went beyond the more prognostically favorable NPM1 and IDH mutant subgroups. Responses to TUS were also observed in those with prior-VEN and prior-FLT3 inhibitor (FLT3i) therapies, those with highly adverse TP53 and RAS mutations, and those with mutated or unmutated (wildtype) FLT3 genes.

The TUSCANY triplet Phase 1/2 study is designed to test various doses and schedules of TUS in combination with standard dosing of AZA and VEN for patients with AML who are ineligible to receive induction chemotherapy. A convenient, once daily oral agent, TUS will be administered in 28-day cycles, beginning at 40 mg once daily, with dose escalations planned after a safety review of each dose level. Multiple U.S. sites are enrolling in the TUSCANY trial with anticipated enrollment of 18-24 patients by mid-late 2025. Data will be released as it becomes available.

In January 2025, Aptose announced the initiation of the TUSCANY trial and dosing in the first cohort of newly diagnosed AML patients with the lowest starting dose (40 mg) of TUS as part of the TUS+VEN+AZA triplet, and the early data reveal promising clinical safety and antileukemic activity:

To date, four newly diagnosed AML patients have received the lowest dose of TUS (40 mg) as part of the (TUS+VEN+AZA) combination.

Three patients with unmutated (wildtype) FLT3 (FLT3-WT) completed Cycle 1 of treatment with no dose-limiting toxicities (DLTs) and no TUS dose adjustments.

Two FLT3-WT patients achieved complete remissions (CR and CRh) by the end of Cycle 1.
Notably, a patient with biallelic TP53 mutations and a complex karyotype obtained CR.

The third FLT3-WT patient experienced significant reductions in bone marrow leukemic blasts during Cycle 1 and remains on therapy in Cycle 2.

The fourth patient, harboring FLT3-ITD and NPM1 mutations, is currently dosing in Cycle 1 and is not yet eligible for response evaluation.

Pharmacokinetic (PK) analyses for TUS show plasma levels unaffected by the addition of AZA, providing predictability and avoiding the need for dose alterations due to PK interactions.
Similarly, VEN plasma levels in Cycle 1 are consistent with published results and the prior TUS/VEN APTIVATE study in R/R AML, indicating no clinically significant interactions with TUS.

More information on the TUSCANY Phase 1/2 study can be found on www.clinicaltrials.gov.