On December 12, 2024 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company that intends to change its name to BeOne Medicines Ltd., reported it has entered into a global licensing agreement with CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. ("CSPC") for SYH2039, a novel methionine adenosyltransferase 2A (MAT2A)-inhibitor being explored for solid tumors (Press release, BeiGene, DEC 12, 2024, View Source [SID1234649091]).

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SYH2039 targets solid tumors that have a mutation called MTAP deletion, which is estimated to be present in approximately 15 percent of all cancer types with the most common including glioblastoma, pancreatic cancer and non-small cell lung cancer.

"With one of the most dynamic solid tumor portfolios in the industry, we are continually assessing opportunities that align with our strategic focus and address significant unmet needs for patients. This MAT2A inhibitor is a valuable addition to our solid tumor pipeline, and we’re eager to explore its potential, particularly in combination with our internally developed PRMT5 inhibitor, BGB-58067. Together, these assets hold promise for advancing treatment across a range of solid tumors," said Lai Wang, Ph.D., Global Head of R&D at BeiGene.

BGB-58067, which is on track to enter the clinic before the end of the year, is designed to avoid on-target hematological toxicity seen with first-generation PRMT5 inhibitors. It has best-in-class potential with high potency, selectivity, and brain penetrability.

Under the terms of the agreement, BeiGene has an exclusive license to develop, manufacture and commercialize SYH2039 worldwide. CSPC will receive upfront and time-based payments totaling $150 million and will be eligible for payments upon the achievement of certain development and commercial milestones and tiered royalties.

BeiGene is focused on growing its leadership in solid tumors with its PD-1 inhibitor TEVIMBRA (tislelizumab) and by advancing potential best-in-class assets for lung, breast and gastrointestinal cancers, including several differentiated antibody drug conjugates, multi-specific antibodies, targeted protein degraders, and small molecule inhibitors. The Company recently announced its intent to change its name to BeOne, reaffirming its commitment to develop innovative medicines to eliminate cancer by partnering with the global community to serve as many patients as possible.

On December 12, 2024 Laekna (2105.HK) reported that the company will present an internally discovered preclinical candidate at the 2024 San Antonio Breast Cancer Symposium (SABCS) on December 13, 2024 (Press release, Laekna Therapeutics, DEC 12, 2024, View Source [SID1234649090]). The presentation will feature preclinical characterization of LAE118, a novel allosteric pan-mutant selective PI3Kα inhibitor.

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"We appreciate this recognition of our expertise and strength in pre-clinical developments of novel drugs", said Dr. Justin Gu, Chief Scientific Officer of Laekna. "The development of LAE118 was led by Dr. Ming Li, with collaborative contributions from the Med Chem, Biology and AIDD (AI-driven Drug Discovery) teams of Laekna. We have significantly accelerated the development of our preclinical drug candidate with cutting-edge artificial intelligence tools".

"As a novel allosteric inhibitor, LAE118 demonstrates excellent potency and selectivity towards various PI3Kα mutants. With superior efficacy and higher tolerability than its competitors in animal models, LAE118 has great potential to become the best-in-class pan-mutant-selective PI3Kα inhibitor. We look forward to bringing this novel therapy to the patients", said Dr. Justin Gu.

PI3Kα mutations are prevalent in patients with breast, colorectal, lung, endometrial, and numerous other cancers. Targeting PI3Kα in cancer has been validated as a therapeutic strategy, as evidenced by the approved drugs. However, the first-generation drugs inhibit the wild-type PI3Kα with equal potency, which raises concerns of tolerability and therapeutic efficacy. Therefore, there is a pressing need to develop novel PI3Kα-targeted therapies that can minimize on-target toxicities and overcome drug resistance.

While making significant progress in pre-clinical developments of drug candidates in cancer, Laekna has also established a comprehensive Activin-ActRII portfolio in metabolism. Following the clinical collaboration with Eli Lilly on LAE102 (ActRIIA selective antibody), Laekna has progressedLAE103, an ActRIIB selective inhibitor and LAE123, a dual inhibitor against ActRIIA/IIB, into IND-enabling studies, aiming to advance them to the clinical stage swiftly.

The San Antonio Breast Cancer Symposium is an annual event cosponsored by the AACR (Free AACR Whitepaper) and UT Health San Antonio’s Mays Cancer Center. The meeting is the largest and most prestigious scientific gathering on breast cancer research.

Presentation details are as follows:

Abstract Number: SESS-3548

Poster Number: P5-06-16

Title: Preclinical characterization of LAE118, a novel allosteric pan-mutant selective PI3Kα inhibitor

Authors: Ming Li, Ruipeng Zhang, Junyan Chen, Meijuan Hu, Xiaofen Lin, Minhua Zhang, Xiang-Ju Justin Gu

Time: Friday, Dec. 13, 2024, 12:30 p.m. – 14:00 p.m. CST

Location: Halls 2-3, Henry B. Gonzalez Convention Center, San Antonio, Texas

Abstract Highlights:

LAE118 is a novel allosteric pan-mutant selective PI3Kα inhibitor. LAE118 demonstrates excellent in vitro anti-proliferation activities in PI3Kα mutant cell lines and remains active against cells resistant to orthosteric PI3Kα inhibitors. LAE118 shows strong anti-tumor growth effect in Xenograft models at a dose that is much lower than other allosteric inhibitors and has less effect on glucose homeostasis compared to orthosteric PI3Kα inhibitors. In pre-clinical toxicology studies, LAE118 also demonstrated good tolerability. These data indicate that LAE118 offers improved efficacy and larger safety window. LAE118 is currently in IND enabling stage and Laekna aims to submit the IND application at the earliest opportunity.

On December 12, 2024 The Menarini Group ("Menarini"), a leading international pharmaceutical and diagnostics company, and Stemline Therapeutics, Inc. ("Stemline"), a wholly-owned subsidiary of the Menarini Group focused on bringing transformational oncology treatments to cancer patients, along with MEDSIR, a leading global independent clinical research company in oncology and part of Oncoclínicas & Co., the largest specialized oncology treatment group in Latin America, reported research on the pioneering clinical trial ADELA (Press release, Menarini, DEC 12, 2024, View Source [SID1234649089]). This important research addresses therapeutic resistance in advanced ER+/HER2- breast cancer. Presented at the San Antonio Breast Cancer Symposium 2024 (SABCS), the study represents a key milestone in the quest for more effective and personalized treatment options for patients with disease progression.

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The standard first-line treatment for advanced ER+/HER2- breast cancer combines endocrine therapy with CDK4/6 inhibitors. ESR1 mutations develop as a result of prior exposure to endocrine therapy during metastatic treatment, and up to 50% of ER+, HER2- advanced or metastatic breast cancers will develop these mutations. ESR1 mutations cause the tumors to become resistant to endocrine therapy, in turn causing the cancer to progress; therefore, it is important to test for ESR1 whenever mBC progresses. Longer exposure to endocrine therapy during first-line treatment increases the chance of a patient’s tumor developing an ESR1 mutation. With the goal of addressing this unmet medical need, the ADELA phase III clinical trial investigates a new therapeutic option combining elacestrant, a next generation, oral selective estrogen receptor degrader, with everolimus, an mTORC1 inhibitor.

This combination is being evaluated in patients with advanced ER+/HER2- breast cancer that harbors ESR1 mutations, and who have experienced progression after standard first-line treatment. Results from the phase III EMERALD study were the basis for elacestrant’s approval. Meanwhile, everolimus has shown efficacy in inhibiting other resistance mechanisms in this type of cancer. The elacestrant and everolimus combination has demonstrated preliminary efficacy with a manageable safety profile in the phase 1b/2 ELEVATE study (NCT05563220).

"We at Menarini Stemline are delighted to announce the collaboration with MEDSIR to continue advancing the clinical research to explore the combination therapy with elacestrant," said Nassir Habboubi, MD, Chief Medical Officer of Stemline Therapeutics. "We are committed to driving innovation in cancer treatment by delivering transformational therapies aiming to extend the lives of people living with cancer."

The primary objective of this international, randomized, double-blind trial is to evaluate whether the combination of elacestrant and everolimus offers greater efficacy in delaying disease progression compared to elacestrant monotherapy. Additionally, it investigates other crucial aspects, such as overall survival, toxicity profile, and the impact on patients’ quality of life.

The ADELA study represents a critical step in understanding how to overcome tumor resistance challenges in patients with ESR1 mutations, with the goal of advancing towards more effective and safer treatments.

"At MEDSIR, we understand innovation not only as achieving clinical results but as the ability to transform patients’ lives on a global scale. With ADELA, we take a decisive step toward accomplishing less invasive and more accessible treatments, aiming to offer new hope to those facing the most complex forms of the disease. This advancement reinforces our commitment to increasingly personalized and patient-centered medicine, a fundamental pillar in shaping the future of oncology," said Dr. Antonio Llombart-Cussac, Senior Scientific Leader at MEDSIR.

The phase III study not only has significant clinical objectives, but also holds the potential to pave the way for regulatory approval of this therapeutic combination, enabling its use in a broader population of patients with advanced breast cancer. Moreover, the international scope of the study, which includes participation from multiple countries, including Spain, Italy, France, Austria, the Czech Republic, Greece, Germany, and the United Kingdom, underscores the study’s global importance and relevance in the scientific community.

The presentation of the ADELA study at an event as prominent as SABCS 2024 reinforces MEDSIR’s leadership in excellence-driven oncology research and highlights its focus on addressing unmet needs in breast cancer treatment. The ADELA study is active and already recruiting patients.

About ORSERDU (elacestrant)

U.S. Indication: ORSERDU (elacestrant), 345 mg tablets, is indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.

Full prescribing information for the U.S. can be found at www.orserdu.com.

Important Safety Information
Warning and Precautions

Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia occurred in patients taking ORSERDU at an incidence of 30% and 27%, respectively. The incidence of Grade 3 and 4 hypercholesterolemia and hypertriglyceridemia were 0.9% and 2.2%, respectively. Monitor lipid profile prior to starting and periodically while taking ORSERDU.

Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, ORSERDU can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the final dose.

Adverse Reactions

Serious adverse reactions occurred in 12% of patients who received ORSERDU. Serious adverse reactions in >1% of patients who received ORSERDU were musculoskeletal pain (1.7%) and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of patients who received ORSERDU, including cardiac arrest, septic shock, diverticulitis, and unknown cause (one patient each).
The most common adverse reactions (≥10%), including laboratory abnormalities, of ORSERDU were musculoskeletal pain (41%), nausea (35%), increased cholesterol (30%), increased AST (29%), increased triglycerides (27%), fatigue (26%), decreased hemoglobin (26%), vomiting (19%), increased ALT (17%), decreased sodium (16%), increased creatinine (16%), decreased appetite(15%), diarrhea(13%), headache (12%), constipation (12%), abdominal pain (11%), hot flush (11%), and dyspepsia (10%).

Drug interactions

Concomitant use with CYP3A4 Inducers and/or inhibitors: Avoid concomitant use of strong or moderate CYP3A4 inhibitors with ORSERDU. Avoid concomitant use of strong or moderate CYP3A4 inducers with ORSERDU.

Use in specific populations

Lactation: Advise lactating women to not breastfeed during treatment with ORSERDU and for 1 week after the last dose.
Hepatic Impairment: Avoid use of ORSERDU in patients with severe hepatic impairment (Child-Pugh C). Reduce the dose of ORSERDU in patients with moderate hepatic impairment (Child-Pugh B).
The safety and effectiveness of ORSERDU in pediatric patients have not been established.

To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

On December 12, 2024 Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel therapies that address emerging targets in oncology, reported an update on clinical progress and data in the Phase II program RVU120, its fully-owned first-in-class dual CDK8/19 inhibitor, currently being developed to treat hematologic malignancies (Press release, Ryvu Therapeutics, DEC 12, 2024, View Source [SID1234649088]).

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Paweł Przewięźlikowski, co-founder and Chief Executive Officer of Ryvu Therapeutics said:

– 2024 has been transformative for RVU120 development plan in hematologic malignancies, marked by activating over 100 clinical sites across Europe and North America. By the year-end, we expect to enroll almost 100 patients across all four Phase II studies launched this year, demonstrating the scale and efficiency of our global clinical efforts. This progress aligns with the budget we planned back in 2023. As we enter 2025, we are poised to carry strong enrollment momentum and the ambition to generate informative efficacy readouts in the coming months.

KEY OVERALL UPDATES

Ryvu successfully launched all four RVU120 Phase II clinical studies planned for 2024: RIVER-52, RIVER-81, POTAMI-61 and REMARK – with all studies progressing on track toward key efficacy analyses in H1 2025.
Study sites: As of December 11, 2024, Ryvu activated 106 clinical sites in Poland, Italy, Spain, France, Germany, and Canada. The Company estimates that across all four RVU120 Phase II studies, 113 sites will have been activated by the end of 2024.
Study enrollment: Enrollment is accelerating, with 78 patients enrolled as of December 11, 2024. Ryvu anticipates dosing ~100 patients by year-end. The pace of recruitment has picked up significantly since September 2024, with nearly three times as many patients expected to be treated in Q4 2024 alone compared to the combined total from Q1 to Q3.
Safety: RVU120 demonstrates a favorable safety profile compared to other drugs used to treat acute myeloid leukemia (AML).
Efficacy:
o In the RIVER-81 study (RVU120 in combination with venetoclax in patients with relapsed/refractory AML, r/r AML, who have failed a previous venetoclax/HMA-based regimen), within eight patients treated with RVU120 at 250 mg (RP2D) that had at least one evaluable post-baseline assessment, one patient achieved a complete remission (CR), and another patient achieved a significant blast reduction. Part 1 of the study (combination dose escalation) was completed, and Part 2 is currently enrolling at the full doses of RVU120 (250 mg) and venetoclax (400 mg).
o In the RIVER-52 study (RVU120 as a monotherapy in patients with r/r AML and high-risk myelodysplastic syndromes; HR-MDS), one of two evaluable patients in cohort 2 (NPM1 mutation) achieved a 50% blast reduction, while disease stabilizations and reduction of peripheral blasts were observed in patients in cohort 3 (DNMT3A mutation).
o Key efficacy readouts in both RIVER-52 and RIVER-81 studies and the first efficacy data in the POTAMI-61 and REMARK trials are expected in H1 2025.
All studies align with the originally planned budgets, while Ryvu’s cash runway guidance to Q1 2026 remains unchanged.
Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics said:

– The growing body of evidence confirms that RVU120 appears to have a favorable safety profile compared to other drugs used for treating similar hematologic malignancies, both in monotherapy and in combination with venetoclax. The RIVER-81 study has progressed to Part 2 with positive signals, including a complete remission in one patient treated with RVU120 at a dose of 250 mg. Similarly, the RIVER-52 study provides early signs of efficacy, but more data are needed to evaluate RVU120 in the targeted population. With increased enrollment, we expect to obtain a representative number of patients in H1 2025. In this timeframe, we also plan to obtain the first efficacy data in the POTAMI-61 and REMARK studies.

ABOUT RVU120 AND UPDATES BY PHASE II STUDY

RVU120 is a selective, first-in-class dual CDK8/19 kinase inhibitor developed by Ryvu Therapeutics. RVU120 as monotherapy has demonstrated clinical activity in a Phase Ib (RIVER-51) study, where 50% of evaluable patients with r/r AML or HR-MDS achieved clinical benefit, including a complete remission, a morphologic leukemia-free state, transition to a bone-marrow transplant, two-year disease stabilization, multiple clinically significant blast reductions, hematologic improvements, and reduction of bone marrow fibrosis. In particular, early signs of efficacy were observed in patients with NPM1 and DNMT3A mutations, as well as in patients with HR-MDS. RVU120 achieved target engagement of 50-70% at a dose of 250 mg, which was selected as a recommended Phase II dose (RP2D). These levels are expected to produce robust antileukemic efficacy in Phase II studies.

Following the announcement of the updated development plan for the RVU120 program in October 2023, Ryvu successfully launched all four planned Phase II studies in hematologic malignancies in 2024 (RIVER-52, RIVER-81, POTAMI-61 and REMARK). Ryvu initiated a global clinical program with the activation as of December 11, 2024, of 106 sites in Poland, Italy, Spain, France, Germany and Canada.

RIVER-81: Phase II study of RVU120 in combination with venetoclax administered to patients with AML who are relapsed or refractory to prior therapy with venetoclax and a hypomethylating agent (NCT06191263).

The RIVER-81 study is a multicenter, open-label clinical trial that aims to assess the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD).

The study is divided into three parts. Part 1 aims to identify safe and tolerated doses of RVU120 and venetoclax when used in combination through dose escalation of both study drugs. In Part 2, the selected doses will be evaluated for safety and efficacy in a larger group of patients. Part 3 is confirmatory. The planned overall enrollment for the study is approximately 35 to 98 patients, depending on the decision on the final scope of the study, driven by the data.

The first patient in the study was dosed on January 31, 2024. Since then, the study has completed Part 1 by progressing through the following dose levels: dose level 1 (125 mg of RVU120 and 200 mg of venetoclax), dose level 2 (200 mg and 200 mg respectively) and dose level 3 (250 mg and 400 mg respectively). RVU120 has demonstrated a consistent safety profile, with no new signals observed when combined with venetoclax at any dose level.

The Company has successfully completed Part 1 of the study and, based on the results, decided to advance it to Part 2, which is currently enrolling. Completion of Stage 1 enrollment for Part 2 (18 patients) is expected in Q1 2025.

The RIVER-81 study was initially launched at the clinical sites in Poland and Italy, followed by the activation of additional sites in Spain and France. As of December 11, 2024, all 33 sites planned for this year had been activated in these countries.

As of December 11, 2024, 28 patients were enrolled, with one patient (within eight patients treated with RVU120 at 250 mg (RP2D) that had at least one evaluable post-baseline assessment) achieving a CR and another achieving a blast reduction to a level below 5%.

RIVER-52: Phase II study of RVU120 as a single agent for the treatment of patients with genetically defined subtypes of AML (including NPM1 and DNMT3A mutations) and HR-MDS who have no alternative treatment options (NCT06268574).

The RIVER-52 study is a multicenter, open-label clinical trial designed to assess the safety, tolerability, anti-tumor activity (efficacy), pharmacokinetics (PK), and pharmacodynamics (PD).

The study is divided into two parts. Part 1 aims to assess the level of anti-tumor activity in patients with genetically defined subtypes of AML, including NPM1 and DNMT3A mutations, as well as in patients with HR-MDS. Based on the outcomes of Part 1, Part 2 will further evaluate the safety, tolerability, and anti-tumor activity in a larger group of patients within the subtypes that exhibit the highest sensitivity to RVU120. The planned overall enrollment is approximately 40 to 140 patients, depending on the decision on the final scope of the study, driven by the data.

The first patient in the study was dosed on February 14, 2024. The RIVER-52 study was initially launched at clinical sites in Poland and Italy. Starting in September 2024, the study expanded to Spain, France and Canada. As of December 11, 2024, 42 out of 44 sites planned for this year had been activated.

As of December 11, 2024, 31 patients were enrolled, including 24 patients in cohorts 2-4 (NPM1-mutated, DNMT3A-mutated, and HR-MDS, respectively). One of two evaluable patients in cohort 2 achieved 50% blast reduction, while disease stabilizations and reductions of peripheral blasts were observed in patients in cohort 3.

Enrollment in the study significantly accelerated in Q4 2024 and is expected to lead to key efficacy readouts in the coming months. Data from at least 10 patients in each cohorts 2-4 are expected in H1 2025.

POTAMI-61: Phase II study of RVU120 as a single agent and in combination with ruxolitinib (RUX) for the treatment of patients with myelofibrosis (MF) (NCT06397313).

The POTAMI-61 study is a multicenter, open-label Phase II study of RVU120, being explored as a single agent for the treatment of patients with primary or secondary MF previously treated with or ineligible for a JAK inhibitor, e.g., ruxolitinib, and in combination with ruxolitinib for patients with suboptimal response to JAK inhibitors. Key endpoints will include spleen volume reduction (SVR), total symptom score (TSS) improvement, and reduction of bone marrow fibrosis.

The study has been initiated based on RVU120’s clinical safety and efficacy data observed in the RIVER-51 (Phase Ib in AML/HR-MDS) study, as well as translational data in MF generated in cooperation with Prof. Raajit Rampal from Memorial Sloan Kettering Cancer Center in New York. In vivo data demonstrate the beneficial effects of CDK8 inhibition in improving symptoms of MF, i.e., splenomegaly, hepatomegaly, anemia, and thrombopenia. Importantly, disease modification properties of RVU120 were shown by the reduction of mutated allele burden. RVU120 can potentially become a novel therapeutic strategy in myeloproliferative neoplasms (MPNs), including MF.

The POTAMI-61 study consists of two parts. Part A of the study, with a planned enrollment of approximately 20 patients, will comprise two cohorts: 1) single-agent therapy with RVU120 in patients resistant or refractory to prior JAK inhibitor treatment or ineligible for JAK inhibitor treatment and 2) RVU120 in combination with RUX in patients who experience a suboptimal response to prior JAK inhibitor treatment. Depending on results from Part A, cohorts 1 and/or 2 could be expanded in Part B, which will further assess safety, tolerability, and antitumor activity in a larger cohort, totaling up to approximately 230 patients for both Part A and Part B combined. RVU120 could also be investigated in a frontline setting in cohort 3. Ryvu will initially proceed with the execution of Part A of the study, while the decision on the potential initiation of Part B will be based on the outcomes of Part A.

The first patient in the study was dosed on December 4, 2024, and five more patients were undergoing screening as of December 11, 2024. Part A of the study will initially enroll patients across clinical sites in Poland and Italy. If Ryvu decides to initiate Part B, the study will expand to include additional sites in the EU and non-EU countries, totaling approximately 50 clinical sites worldwide. As of December 11, 2024, 12 out of 17 sites planned for this year had been activated.

Initial efficacy data is expected in Q2 2025, based on a 12-week patient observation period.

REMARK: Phase II study of RVU120 as a single agent for the treatment of patients with lower-risk myelodysplastic syndromes (LR-MDS) (NCT06243458)

The REMARK study is a multicenter, open-label Phase II study of RVU120, conducted as an investigator-initiated trial with the European Myelodysplastic Neoplasms Cooperative Group (EMSCO), with Prof. Uwe Platzbecker serving as the Coordinating Principal Investigator (CPI).

REMARK has been initiated based on the clinical safety and efficacy data gathered so far, and strong preclinical and mechanistic rationale.

MDS pathogenesis is influenced by gene expression alterations that hinder the maturation of hematopoietic cells. RVU120 triggers erythroid gene expression programs orchestrated by STAT5 and GATA1 in aberrant stem cells from MDS patients. Importantly, RVU120’s activity does not lead to significant hematopoietic toxicity. As a result, RVU120 is a promising drug candidate for treating transfusion-dependent MDS patients.

In the REMARK study, the planned overall enrollment is approximately 40 patients who receive RVU120 for at least 8 complete cycles (24 weeks). The primary goal is to achieve hematologic improvement in the form of an erythroid response (HI-E), with secondary goals including independence from RBC transfusions, improvement in hemoglobin levels, quality of life, disease progression, and analysis of specific gene mutations.

The first patient in the study was dosed on September 19, 2024, and as of December 11, 2024, 18 patients were treated. Patient enrollment commenced across five countries: Poland, Germany, France, Spain and Italy. As of December 11, 2024, 19 out of a planned total of 24 sites were activated.

Initial efficacy data is expected in Q2 2025, based on a 16-week observation period.

NEXT STEPS AND UPCOMING NEWSFLOW

RVU120 Phase II data update in Q2 2025. Following the key efficacy data expected in H1 2025, Ryvu plans to update stakeholders on the clinical progress of RVU120 in Q2 2025.

On December 12, 2024 Intensity Therapeutics, Inc. ("Intensity" or "the Company") (Nasdaq: INTS), a late-stage clinical biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumorally injected cancer therapies intended to kill tumors directly and increase immune system recognition of cancers, and The Swiss Group for Clinical Cancer Research SAKK ("SAKK"), a decentralized academic research institute that has been conducting clinical trials of cancer treatments in all major Swiss hospitals since 1965, reported that Andreas Mueller, M.D., Past-President of the Project Group Breast Cancer of SAKK and Head of the Breast Center at Kantonsspital Winterthur, Switzerland and a supporting coordinating investigator for the study presented in an evening poster session on December 11 the final data from Intensity’s INVINCIBLE-2 Study (NCT04781725), and an overview / update of the INVINCIBLE-4 Study (NCT06358573) at the San Antonio Breast Cancer Symposium being held December 10-13, at the Henry B. Gonzalez Convention Center in San Antonio, Texas (Press release, Intensity Therapeutics, DEC 12, 2024, View Source [SID1234649087]).

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The INVINCIBLE-4 Study is a randomized open-label, multicenter study to determine the clinical activity, safety, and tolerability of INT230-6 in patients with early-stage, operable Triple Negative Breast Cancer ("TNBC") who undergo standard of care neoadjuvant immunochemotherapy ("SOC") treatment and SOC alone. The primary endpoint is pathological complete response ("pCR") in the primary tumor and affected lymph nodes. Patients will be randomized one to one to receive a regimen of either two doses of INT230-6 followed by SOC, which consists of pembrolizumab, anthracyclines, carboplatin, cyclophosphamide, and paclitaxel (i.e. the Keynote-522 regimen), or the SOC alone. The study is recruiting and expected to enroll 54 patients.

"Women with aggressive forms of breast cancer, such as TNBC, are often counseled to undergo pre-surgical (neoadjuvant) systemic therapy in advance to reduce the risk of the disease returning. Having a pathological complete response, meaning the absence of live cancer at the time of surgery, has been shown to result in a lower risk of recurrence. When the tumor diameters are bigger than two centimeters, recurrence is more likely, so that neoadjuvant treatment is warranted" said Dr. Mueller. "If the immunological cancer cell death caused by INT230-6 and the ignition of an anti-cancer immune response without increased toxicity shows a meaningful increase in pCR, it would be a major advance for the neoadjuvant treatment of breast cancer and potentially other cancers. Further, if the results of this study are highly favorable, perhaps the cardiotoxic anthracycline drugs could be reduced or eliminated in future studies."

The Company’s completed INVINCIBLE-2 Study, where INT230-6 was given alone in multiple tumor types including TNBC, showed several benefits:

Tumor-killing properties at levels greater than 95% in some patients on a single intratumoral dose with systemic immune activation.
Results in tumors larger than 2 cm showed significant necrosis in 74% of subjects at the time of surgery.
Gene expression analysis showed a significant difference between baseline biopsies and surgical specimens. Pathway analysis identified genes associated with TCR signaling, B-cell and T-cell activation, with increasing effects in post-treatment samples (SABCS 2023 #PS16-03).
The study demonstrated pathologic and immune priming effects of intratumoral cytotoxicity in traditional immune quiescent breast cancers, with a treatment that showed favorable safety and was well tolerated.
INT230-6 patients had significant differential gene expression present and identified genes were associated with T cell activation, lymphocyte activation and inflammatory response.
INT230-6 patients had increases in CD4 T cells and NK cells within the tumor, and associated changes in the diversity of T cell repertoire.
About INT230-6
INT230-6, Intensity’s lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRx℠ technology platform. The drug is comprised of two proven, potent anti-cancer agents, cisplatin and vinblastine sulfate, and a penetration enhancer molecule (SHAO) that helps disperse potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor, resulting in a favorable safety profile. In addition to local disease control and direct tumor killing, INT230-6 causes a release of a bolus of neoantigens specific to the malignancy, leading to immune system engagement and systemic anti-tumor effects. Importantly, these effects are mediated without immunosuppression, which often occurs with systemic chemotherapy.