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Elevation Oncology Presents Preclinical Proof-of-Concept Data Supporting Combination Potential of EO-3021 with VEGFR2 or PD-1 Inhibitors at ESMO Immuno-Oncology Annual Congress 2024

On December 5, 2024 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported new preclinical data demonstrating the combination potential of EO-3021, a Claudin 18.2 antibody-drug conjugate (ADC), with VEGFR2 or PD-1 inhibitors (Press release, Elevation Oncology, DEC 5, 2024, View Source [SID1234648844]). The data will be presented in a poster session at the European Society for Medical Oncology Immuno-Oncology Annual Congress 2024 (ESMO-IO), being held December 11-13, 2024, in Geneva, Switzerland.

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"We are pleased to share preclinical data supporting our planned evaluation of EO-3021 in combination with VEGFR2 or PD-1 inhibitors," said David Dornan, Ph.D., Chief Scientific Officer of Elevation Oncology. "The data demonstrate enhanced anti-tumor activity for both regimens, highlighting the potential benefits of a combination approach. This is particularly encouraging given our previously announced, promising initial clinical data from our Phase 1 clinical trial of single-agent EO-3021, which suggest EO-3021 potentially offers competitive efficacy and differentiated safety profile, including minimal payload-associated toxicity. We look forward to initiating dosing in the combination portion of our ongoing Phase 1 clinical trial of EO-3021 in the fourth quarter and unlocking the full potential of EO-3021 as an active, more combinable Claudin 18.2 ADC."

In a poster titled, "Combination potential of EO-3021, a CLDN18.2 vc-MMAE ADC, with VEGFR2 or PD-1 inhibition in preclinical models of CLDN18.2-expressing cancers," Elevation Oncology will present new in vivo data from preclinical studies evaluating the anti-tumor activity of EO-3021 with a VEGFR2 or PD-1 inhibitor. The data show:

Treatment with EO-3021 and DC101, a surrogate of the VEGFR2 inhibitor ramucirumab, exhibited statistically superior tumor growth inhibition (TGI) compared to treatment with either EO-3021 or DC101 alone (TGI: 88.2% for EO-3021 in combination with DC101, compared to 20.1% for EO-3021 and 59.2% for DC101 alone).
Treatment with EO-3021 and a PD-1 inhibitor exhibited statistically superior TGI compared to treatment with either EO-3021 or a PD-1 inhibitor alone (TGI: 79.9% for EO-3021 in combination with a PD-1 inhibitor, compared to 33.8% for EO-3021 and 25.0% for a PD-1 inhibitor alone). 92% (11/12) of mice treated with the combination of EO-3021 and a PD-1 inhibitor achieved a complete response (CR), compared to 50% (6/12) mice treated with EO-3021 monotherapy and 17% (2/12) mice treated with a PD-1 inhibitor alone.
Elevation Oncology expects to initiate dosing in the combination portion of its ongoing Phase 1 clinical trial of EO-3021 in the fourth quarter of 2024. Following clinical supply agreements with Lilly and GSK, the combination cohorts will evaluate EO-3021 and ramucirumab, a VEGFR2 inhibitor, in patients with gastric/GEJ cancer in the second-line setting, and EO-3021 and dostarlimab, a PD-1 inhibitor, in the front-line setting. Additionally, Elevation Oncology continues to enroll patients in the monotherapy dose expansion portion of its ongoing Phase 1 clinical trial and expects to report additional monotherapy data in the first half of 2025. In August 2024, Elevation Oncology reported initial clinical data from the dose escalation portion of the monotherapy study, demonstrating an objective response rate of 42.8% in patients with Claudin 18.2 in ≥20% of tumor cells at IHC 2+/3+, with differentiated safety profile, including minimal hematological toxicity or hepatotoxicity, and no peripheral neuropathy/hypoesthesia.

The ESMO (Free ESMO Whitepaper)-IO poster presentation will be available in the "Publications" section of Elevation Oncology’s website starting December 12, 2024.

About EO-3021

EO-3021 is a differentiated, clinical-stage, potentially best-in-class ADC comprised of an immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets Claudin 18.2 and a monomethyl auristatin E (MMAE) payload with a cleavable linker that is site-specifically conjugated to Glutamine 295 providing a drug-to-antibody ratio (DAR) of 2. Claudin 18.2 is a specific isoform of Claudin 18 that is normally expressed in gastric epithelial cells. During malignant transformation, the tight junctions may become disrupted, exposing Claudin 18.2 and allowing them to be accessible by Claudin 18.2 targeting agents. Elevation Oncology is evaluating EO-3021 in the dose expansion portion of a Phase 1 trial (NCT05980416) in patients with advanced, unresectable or metastatic gastric/GEJ adenocarcinoma that express Claudin 18.2. Following recently signed clinical supply agreements with Lilly and GSK, respectively, Elevation Oncology will evaluate EO-3021 in combination with ramucirumab, a VEGFR2 inhibitor, in the second-line setting and in combination with dostarlimab, a PD-1 inhibitor, in the front-line setting.

In September 2024, EO-3021 was granted Fast Track designation by the FDA for the treatment of patients with advanced or metastatic gastric/GEJ cancer expressing Claudin 18.2 that has progressed on or after prior therapy. EO-3021 was granted orphan drug designation by the FDA for the treatment of gastric cancer (including cancer of gastroesophageal junction) in November 2020 and for the treatment of pancreatic cancer in May 2021.

Elevation Oncology has the exclusive rights to develop and commercialize EO-3021 in all global territories outside Greater China.

Ryvu Therapeutics Announces Dosing of the First Patient in the POTAMI-61 Phase II Study of RVU120 for the Treatment of Patients with Myelofibrosis (MF)

On December 5, 2024 Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, reported that the first patient had been dosed in the POTAMI-61 study, a Phase II clinical trial investigating RVU120 in the treatment of patients with myelofibrosis (MF) (Press release, Ryvu Therapeutics, DEC 5, 2024, View Source [SID1234648843]).

Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics, said:

"We are excited to announce the initiation of the RVU120 Phase II study, POTAMI-61, the fourth Phase II clinical trial included in the RVU120 development plan that Ryvu presented last year. Based on RVU120’s effect on bone marrow and hematopoietic cells observed in the RIVER-51 study and translational data generated in myelofibrosis with Prof. Raajit Rampal from Memorial Sloan Kettering Cancer Center in New York, we believe there is a strong rationale for RVU120 in the treatment of patients with myelofibrosis, both as a monotherapy and in combination with JAK inhibitors. The favorable RVU120 safety profile may enable targeting patients with unmet medical needs, e.g., patients who are not eligible for or who show a suboptimal response to JAK inhibitor treatment. Additionally, synergy in translational studies indicates potential for use in the frontline setting."

The POTAMI-61 study is an open-label, multicenter Phase II study of RVU120, a novel small-molecule cyclin-dependent kinase (CDK) 8/19 inhibitor, to treat patients with MF. In the POTAMI-61 study, RVU120 is 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. ruxolitnib, or in combination with RUX for patients with suboptimal response to JAK inhibitors. Key endpoints will be spleen volume reduction (SVR), total symptom score (TSS) improvement, and bone marrow fibrosis reduction.

The study is being initiated based on RVU120’s clinical safety and efficacy data, and strong preclinical and mechanistic rationale. In vivo data demonstrate the beneficial effects of CDK8 inhibition on the improvement of symptoms, i.e., splenomegaly, hepatomegaly, anemia, and thrombopenia. Importantly, disease modification properties of RVU120 were shown by the reduction of mutated allele burden. RVU120 has the potential to become a novel therapeutic strategy in myeloproliferative neoplasms, including MF.

In the POTAMI-61 study, patients will receive RVU120 until disease progression, withdrawal of consent or other reasons specified in the study protocol. 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.

Initially, Part A of the study will enroll patients at clinical sites in Poland and Italy. If the Ryvu Management Board decides to initiate Part B, the study will expand to include additional sites both in the EU and non-EU countries, totaling approximately 50 clinical sites worldwide.

POTAMI-61 represents the fourth planned RVU120 Phase II clinical study launched in 2024. Ryvu is already treating patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (HR-MDS) in the RIVER-52 and RIVER-81 studies, as a single agent or in combination with venetoclax. RVU120 is also being investigated in the REMARK study for the treatment of patients with lower-risk myelodysplastic syndromes (LR-MDS).

POTAMI-61 is part of RVU120’s Development Plan presented in October 2023 and aligns with the company’s cash runway. Clinical trials conducted in various hematological indications and treatment regimens (monotherapy and combination therapy) will contribute to the global RVU120 safety database, supporting potential future regulatory approvals.

MEDSIR showcases the DEMETHER Study: advancing therapeutic de-escalation and more effective treatments for advanced breast cancer

MEDSIR, a leading company dedicated to advancing independent clinical research in oncology on an international level and part of Oncoclínicas & Co, the largest oncology treatment group in Latin America with significant strength in the clinical and outpatient setting, reported it will participate in the prestigious San Antonio Breast Cancer Symposium 2024 (SABCS) with the presentation of five innovative studies, including one of particular significance in advanced breast cancer: the DEMETHER study (Press release, MedSIR, DEC 5, 2024, View Source [SID1234648842]). These landmark studies demonstrate remarkable progress in the development of more personalized and less invasive therapies, offering the potential to enhance patients’ quality of life and redefine the treatment approach for advanced breast cancer.

The DEMETHER clinical trial explores an innovative treatment strategy for previously untreated HER2-positive advanced breast cancer. The study employs a dual-phase approach, beginning with an induction phase using trastuzumab deruxtecan (T-DXd), followed by a maintenance phase with subcutaneous administration of trastuzumab and pertuzumab. This strategy aims to prolong progression-free survival, improve overall survival rates at three years, and provide enhanced safety and quality of life compared to standard treatments.

By offering an alternative to conventional chemotherapy and prolonged T-DXd administration, DEMETHER aims to redefine therapeutic de-escalation. This strategy seeks to minimize the side effects associated with traditional therapies, thereby significantly improving patients’ quality of life. Furthermore, it underscores a commitment to making advanced breast cancer treatments more accessible, less invasive, and patient centered.

23 active centers in 4 countries and several Highly Cited Researchers 2024

The trial is currently being conducted at 23 active centers across the United States, Spain, Italy and Germany. Additionally, the study benefits from the involvement of leading international researchers renowned for their excellence. Among them are several scientists featured in the Highly Cited Researchers 2024 list by Clarivate, including Dr. Javier Cortés, Dr. Hope Rugo, Dr. Nadia Harbeck, Dr. Sara M. Tolaney, and Dr. Peter Schmid, whose expertise and contributions bring exceptional value to the project.

The DEMETHER study seeks to further advance personalized medicine, exploring less invasive, safer, and potential more effective alternatives to conventional treatments. "This study reflects the collaborative efforts of international experts, leading centers, the pharmaceutical industry and MEDSIR in designing therapeutic strategies that enhance patients’ quality of life through treatment de-escalation." highlights Dr. Javier Cortés, principal investigator of the DEMETHER study.

New therapeutic options for patients with metastatic breast cancer: exploring advances in brain metastases with PHENOMENAL and TUXEDO-4

Both the PHENOMENAL and TUXEDO-4 studies presented at SABCS are particularly relevant as they address a critical and historically underserved population: patients with metastatic breast cancer (MBC) and brain metastases (BMs). BMs occur in up to 25% of patients with MBC 1, significantly impacting prognosis and quality of life.

These studies stand out by exploring innovative therapeutic strategies tailored to overcome the unique challenges of treating brain metastases. The PHENOMENAL study focuses on nanoliposomal irinotecan, Nal-IRI, to enhance drug delivery to brain tumors while reducing systemic toxicity. Meanwhile, the TUXEDO-4 study investigates the use of T-DXd, a novel antibody-drug conjugate targeting HER2-low tumors, with the goal of achieving meaningful intracranial tumor shrinkage.

An innovative therapeutic regimen with the potential to expand treatment options and improve the quality of life for patients with advanced breast cancer

The Phase III ADELA study, in collaboration with the MENARINI Group, explores new perspectives in the treatment of advanced ER+ and HER2-negative breast cancer, specifically in patients with mutations in the ESR1 gene whose cancer has progressed after receiving standard first-line of therapy. This gene produces estrogen receptor proteins that can stimulate the growth of this type of breast cancer.

ADELA has the potential, if successful, to pave the way for regulatory approval of this therapeutic combination, making it accessible to a broader patient population.

In addition to this study, MEDSIR is presenting the PRIMED trial, which evaluates the efficacy of prophylactic administration of granulocyte colony-stimulating factor (G-CSF) and loperamide during the initial treatment cycles of sacituzumab govitecan (SG) therapy to mitigate the incidence of neutropenia and diarrhea, aiming to enhance treatment tolerability and patient safety.

The presentation of these results at an event of SABCS 2024’s magnitude not only positions MEDSIR as a leader in oncology research excellence but also highlights its ability to lead transformative projects addressing unmet needs in breast cancer treatment.

Ono Enters into Drug Discovery Collaboration Agreement with Congruence Therapeutics to Generate Novel Small Molecule Correctors in the Oncology Area

On December 5, 2024 Ono Pharmaceutical Co., Ltd. (Headquarters: Osaka, Japan; President: Toichi Takino; "Ono") reported that it has entered into a drug discovery collaboration agreement with Congruence Therapeutics (Headquarters: Montreal, Quebec, Canada; CEO: Clarissa Desjardins; "Congruence") to generate novel small molecule correctors against multiple protein targets in the oncology area by leveraging Congruence’s proprietary drug discovery platform, Revenir (Press release, Ono, DEC 5, 2024, View Source [SID1234648841]).

Under the terms of the agreement, Congruence will generate small molecule correctors by leveraging Congruence’s proprietary drug discovery engine called, Revenir. Ono will obtain an exclusive option right to develop, manufacture and commercialize the identified small molecule correctors worldwide. Congruence will be eligible to receive an upfront payment, research expenses, milestone payments based on research and development progress and sales, as well as tiered royalties based on net sales.

"We believe that this collaboration with Congruence may help generating novel small molecule correctors for validated targets in the oncology area by leveraging their own technologies in protein dynamics and computational biology, leading to our development pipeline," said Seishi Katsumata, Corporate Officer / Executive Director, Discovery & Research of Ono. "We will be committed to delivering innovative new drugs to cancer patients as soon as possible."

"Congruence is thrilled to partner with Ono, which has established itself as a global leader in drug development, particularly in the oncology space. We believe that our Revenir platform and capabilities in protein dynamics will accelerate the discovery of novel therapies for compelling targets of interest to both companies," said Sharath Hegde PhD, Chief Scientific Officer of Congruence.

About Revenir Drug Discovery Platform

Revenir, Congruence’s proprietary computational drug discovery platform, captures the dynamic biophysical changes caused by mutations in proteins, offering unique insights into protein defects and their correction. By examining surface features and a spectrum of biophysical descriptors across an ensemble of protein conformers, Revenir predicts small molecule induced correction of the underlying defect.

Duality Biologics and BioNTech Presented Positive Interim Data for Investigational B7-H3 Antibody-Drug Conjugate BNT324/DB-1311 in Advanced Solid Tumors at the ESMO Asia Congress 2024

On December 5, 2024 Duality Biologics ("DualityBio") reported first data from a global Phase 1/2a clinical trial (NCT05914116, CTR20232835) evaluating BNT324/DB-1311, an investigational next-generation antibody-drug conjugate ("ADC") targeting the transmembrane glycoprotein B7-H3 (Press release, DualityBio, DEC 5, 2024, View Source [SID1234648840]). The data were presented in an oral session at the 2024 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia Annual Meeting ("ESMO Asia") in Singapore and showed encouraging antitumor activity alongside a manageable safety profile in heavily pretreated patients with locally advanced or metastatic solid tumors. BNT324/DB-1311 is being co-developed by BioNTech SE (Nasdaq: BNTX, "BioNTech") and DualityBio.

The analysis of the ongoing Phase 1/2a trial included 277 participants across various solid tumor types including small cell lung cancer ("SCLC"), non-small cell lung cancer ("NSCLC"), castration-resistant prostate cancer ("CRPC"), and squamous cell carcinoma of the head and neck ("SCCHN"). About 75% of participants had an Eastern Cooperative Oncology Group ("ECOG") performance status of 1, and approximately 61% had undergone two or more lines of therapy. The primary endpoints of the trial are safety and objective response rate ("ORR") as determined by investigator. The secondary endpoints include duration of response ("DoR"), disease control rate ("DCR"), progression-free survival ("PFS"), overall survival ("OS") among others. The data showed the following results:

Among all evaluable patients with at least one post-baseline tumor assessment (n=238), the overall uORR was 32.4%, and the DCR was 82.4%.
Among patients with SCLC (n=73), the uORR was 56.2%, and the DCR was 89.0%. The majority of patients with SCLC received 6 mg/kg and 9 mg/kg of BNT324/DB-1311, with no difference in uORR between the two dose groups (54.5% and 58.8%, respectively). Notably, at the 9 mg/kg dose level, the uORR in patients with SCLC who had prior immunotherapy but no treatment with topoisomerase I inhibitors reached 70.4%.
Most patients with NSCLC had non-squamous histology (n=41), exhibiting an uORR of 22.0%, while patients with squamous NSCLC (n=25) had an uORR of 16.0%.
Among patients with CRPC (n=32), BNT324/DB-1311 demonstrated early antitumor activity with an uORR of 28.0% and a DCR of 92.0%. With a median rPFS of 7.2 months, the rPFS data were not mature at the time of the analysis. The 6-month rPFS rate was 94.7%.
In other tumor types, including cervical cancer (n=4), hepatocellular carcinoma (n=12), head and neck squamous carcinoma (n=3), and melanoma (n=11), BNT324/DB-1311 also exhibited antitumor activity with uORRs of 75.0%, 25.0%, 100.0%, and 36.4%, respectively.
BNT324/DB-1311 showed a manageable safety profile across all evaluated patients and tumor types (n=277). The most common treatment-related adverse events (TRAEs) reported included nausea, neutrophil count decreased, anemia, white blood cell count decreased, decreased appetite, and platelet count decreased.
Dr. John Zhu, Founder and CEO of Duality Biologics, said, "BNT324/DB-1311 is an innovative ADC molecule co-developed by BioNTech and DualityBio, showing clinical data in the study phase. This early data supports DualityBio’s ADC technology platform, and the continued research and development of novel ADC therapies with the aim to improve the standard of care, and embodying DualityBio’s commitment to exploring innovative treatments while advancing the global ADC industry for patient benefit."

BNT324/DB-1311 is one of three clinical stage ADC candidates in BioNTech’s and DualityBio’s global strategic partnership aimed at advancing these novel ADC assets into late-stage development in multiple high unmet medical need cancer indications. Multiple clinical trials combining selected assets from BioNTech’s and DualityBio’s strategic partnership with BNT327/PM8002, a novel investigational bispecific antibody targeting PD-L1 and VEGF-A, which is being jointly developed by BioNTech and Biotheus are planned in various solid tumor indications. A Phase 1/2 clinical trial evaluating the combination of BNT325/DB-1305, a TROP2 targeting ADC candidate, and BNT327/PM8002 is currently ongoing. A Phase 1/2 trial evaluating BNT324/DB-1311 in combination with BNT327/PM8002 in patients with SCLC or NSCLC is planned to start in 2025.

About BNT324/DB-1311

BNT324/DB-1311 is a next-generation topoisomerase-I-inhibitor-based ADC candidate targeting the immune checkpoint protein B7-H3. The transmembrane glycoprotein B7-H3 plays a critical role in the anti-tumor immune response and the shaping of the tumor microenvironment. It is overexpressed in a range of solid tumors, with limited expression in healthy tissues, and has been associated with disease progression and very poor prognosis.[i] Preclinical studies have shown that BNT324/DB-1311 exhibits antitumor activity in various solid tumor models.[ii] Preliminary data from the ongoing Phase 1/2a trial (NCT05914116) has demonstrated antitumor activity and a manageable safety profile for BNT324/DB-1311 in patients with advanced solid tumors.

In June 2024, the U.S. Food and Drug Administration ("FDA") granted Fast Track designation for BNT324/DB-1311 for the treatment of patients with advanced/unresectable, or metastatic castration-resistant prostate cancer ("CRPC"). In July 2024, the FDA granted Orphan Drug Designation to BNT324/DB-1311 for the treatment of advanced or metastatic esophageal squamous cell carcinoma.