On April 9, 2024 Jacobin Pharma (1167.HK), a clinical-stage oncology company focusing on undruggable targets, reported that the company will present the results of two preclinical evaluation of PARP7 inhibitor JAB-26766 and p53 Y220C reactivator JAB-30355 in form of the abstract during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 (the "AACR 2024") from April 5 to 10, 2024 (Press release, Jacobio Pharmaceuticals, APR 9, 2024, View Source [SID1234641955]).

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Dr. Andrea Wang-Gillam, Chief Medical Officer and Global Head of R&D of Jacobio Pharma, said: " The preclinical data of the two drugs are representatives of our continued efforts in developing drugs toward key oncogenic pathways. P53 Y220C is the first tumor suppressor gene to enter into clinical study and has the potential to be used in combination with chemotherapy or oncogenic protein inhibitors. As an important downstream target of the STING signaling pathway, PARP7 is expected to be used in combination with immunotherapy in the future. Jacobio is committed to developing both assets globally."

Details for the 2024 AACR (Free AACR Whitepaper) abstracts are as follows:

JAB-26766: a small-molecule, orally bioavailable PARP7 inhibitor with high potency and selectivity
Poster Presentation: April 9, 2024, 9:00 AM – 12:30 PM (GMT-7)
Session: PO.ET09.01 – DNA Reactive Agents

JAB-26766 is a potent, orally bioavailable PARP7 inhibitor with >1800-fold selectivity on PARP7 over PARP2. JAB-26766 as a single agent shows potent in vivo anti-tumor activities, which can be further enhanced through combination with STING agonist or anti-PD-1 mAb.

JAB-30355: A highly potent, orally bioavailable p53 Y220C reactivator
Poster Presentation: April 9, 2024, 1:30 PM – 5:00 PM (GMT-7)
Session: PO.ET09.09 – Novel Antitumor Agents 4

JAB-30355 is a potent and selective p53 Y220C reactivator. JAB-30355 exhibited dose-dependent anti-tumor activity, inducing tumor stasis or regression in multiple CDX and PDX models of ovarian cancer, pancreatic cancer, gastric cancer, and small cell lung cancer, with overall good tolerability. A phase I/IIa clinical trial to evaluate the safety and efficacy of JAB-30355 in patients with advanced solid tumor is ongoing in U.S.

The 2024 AACR (Free AACR Whitepaper) Annual Meeting will be held in San Diego, California, U.S. from April 5th to April 10th. For more information, please visit the official website of the AACR (Free AACR Whitepaper): View Source

On April 9, 2024 Aadi Bioscience, Inc. (NASDAQ: AADI), a commercial-stage precision oncology company focused on developing and commercializing therapies for cancers with alterations in the mTOR pathway, reported it will present new non-clinical data that highlight the combinability of nab-sirolimus and its potential for synergy to enhance anti-cancer effects and overcome resistance (Press release, Aadi Bioscience, APR 9, 2024, View Source [SID1234641954]). These data will be presented during poster sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in San Diego, CA, taking place April 5-10, 2024.

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Poster presentation details and abstract highlights include:

Title: "Evaluation of nab-sirolimus in combination with fulvestrant or PI3K pathway inhibitors to overcome resistance in breast cancer cell lines"
Presenting Author: Shihe Hou, PhD
Session Title: Reversal of Drug Resistance
Poster Number: Poster Section 25; Poster 6
Date/Time: Wednesday, April 10, 2024, 9:00 AM – 12:30 PM

Fulvestrant, the selective estrogen receptor degrader and PI3K inhibitors, such as alpelisib, have demonstrated efficacy in patients with HR+ PI3K-mutated breast cancer; however, resistance still occurs
nab-sirolimus enhanced the cytotoxic effects of fulvestrant in HR+ breast cancer cells and PI3Ki in both HR+ and HR- breast cancer cells
The addition of nab-sirolimus to endocrine therapy or PI3K-AKT-mTOR pathway inhibitors may mutually overcome mechanisms of resistance induced by single-agent treatments
These data further support the combination of nab-sirolimus with endocrine therapy for hormone-driven cancers, as is currently being investigated in patients with advanced or recurrent endometrioid endometrial cancer in a Phase 2 study (NCT05997017)
Title: "Correlation of nab-sirolimus tumor drug levels and improved tumor suppression in KRAS G12C non-small cell lung cancer xenografts treated with nab-sirolimus in combination with KRAS inhibitors"
Presenting Author: Shihe Hou, PhD
Session Title: Targeting Kinase and ERK Pathways
Poster Number: Poster Section 46; Poster 3
Date/Time: Tuesday, April 9, 1:30 – 5:00 PM

Corresponding with greater antitumor activity, nab-sirolimus was associated with higher intratumoral drug concentration and stronger mTOR target suppression than everolimus when the agents were combined with KRAS G12C inhibitors
These findings suggest more efficient tumor-targeting with nab-sirolimus plus a KRAS G12C inhibitor may lead to improved target inhibition and improved clinical outcomes

On April 9, 2024 BioCity Biopharma reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for a Phase 1 study of BC2027 (Press release, Biocity Biopharmaceutics, APR 9, 2024, View Source [SID1234641953]). BC2027, which is BioCity’s second first-in-class antibody drug conjugate (ADC) approved for clinical development, targets Glypican 3 (GPC3), a proteoglycan found in the outer membrane of cancer cells. BioCity’s first ADC, BC3195, which is directed against another novel target called placental-cadherin (CDH3), a cell adhesion molecule that confers invasiveness and metastatic properties to cancer cells, is also in clinical trials.

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GPC3 is specifically up-regulated in the most common type of liver cancer, hepatocellular carcinoma (HCC), several types of lung and esophageal cancer, and other malignancies, although rarely or not expressed in normal liver tissues, making GPC3 a rational treatment target for cancers that express it. Recently, clinical activity has been noted with chimeric antigen receptor (CAR) T cells and other therapies targeting GPC3, demonstrating the potential of GPC3 as a therapeutic target.

BC2027 binds with very high affinity to GPC3 and efficiently internalizes into cancer cells where it releases its cancer killing payload. In addition to directly killing cancers cells in which it enters, BC2027’s cancer activity is enhanced as it kills other cancer cells indirectly via a "bystander effect". In preclinical studies, BC2027 was also quite safe and tolerable while demonstrating robust anticancer activity with greater than 90% inhibition of tumor growth in some well-established cancers. These findings indicate the potential for BC2027 to be a novel, safe, and effective cancer treatment.

The uniqueness of GPC3 as a target also suggests that BC2027 may in part overcome the challenges of cancer drug resistance. Dr. Yong Jiang Hei, CEO of BioCity, noted that "Drug resistance has increasingly become a challenge in cancer treatment. BioCity aims to develop next generation therapies with the potential to delay and overcome drug-resistance. Among different strategies, developing novel ADCs is an important approach to address the inherent drug resistance of HCC and many other cancers, as well as secondary drug resistance resulting from available anticancer therapies." He added, "Now BioCity has two first-in-class, novel ADCs in global clinical development, thereby resulting in a competitive edge as BioCity’s ADCs are clearly differentiated. The company will strive to advance the clinical development of these exciting ADC therapeutics to meet the unmet clinical needs and benefit patients worldwide as early as possible." Dr. Hei says.

HCC and GPC3

Liver cancers are highly prevalent worldwide with approximately 860,000 newly diagnosed cases and 750,000 ①deaths annually. Among liver cancers, 90% are HCC. In addition, the poor prognosis of the disease represents a significant unmet medical need.

In recent years, with the rapid development of systemic therapies for HCC, the standard of care for advanced HCC has evolved from traditional chemotherapy to multi-kinase inhibitors and immune checkpoint inhibitors, or the combination of the two. However, the efficacy of these therapies is limited and further advances in treatment are urgently needed.

GPC3 is highly expressed in more than 70% HCC and the expression level correlates with the extent of disease progression. Therefore, GPC3 is a specific tumor marker and closely related to disease prognosis, making it a promising target for the treatment of HCC②.

On April 9, 2024 MEDSIR, a leading company dedicated to the strategic design of independent clinical research, reported in the Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), a premier event that brings together scientists, clinicians, industry professionals, advocates, and other stakeholders in the field of cancer research, presenting the results of two sub-studies focused on biomarkers: transFal, focused on patients with HR+/HER2- advanced breast cancer and METSGain, centered on patients with early breast cancer (Press release, MedSIR, APR 9, 2024, View Source [SID1234641952]).

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Both studies underscore the importance of utilizing biomarkers. Their early detection has been shown to increase patient survival rates by aiding in selecting the most appropriate treatment for patients.

In the context of personalized medicine, biomarkers are also important for tailoring treatments for individual patients based on their unique biological characteristics, allowing for more precise and effective medical interventions.

MEDSIR’s mission is to improve therapeutic responses, thereby enhancing patient lives. Through translational studies that use samples from groundbreaking trials, such as PARSIFAL and PHERGain, MEDSIR aims to elevate clinical practice for the benefit of patients.

Mario Mancino, PhD, Translational Research Manager at MEDSIR, expressed enthusiasm: "We are thrilled to present our research at the Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). Our commitment to advancing personalized medicine through biomarkers underscores our dedication to improving patient outcomes."

These findings represent significant strides in understanding and leveraging biomarkers for personalized cancer care, offering new hope to patients and paving the way for more effective treatment strategies tailored to individual patients’ biological profiles.

transFAL: Unlocking Biomarkers for HR+/HER2- Advanced Breast Cancer

MEDSIR introduced the results of the transFAL study, aimed at uncovering biomarkers of response or resistance to palbociclib in combination with endocrine therapy-based regimens for patients with HR+/HER2- advanced breast cancer. The study, analyzing samples from the PARSIFAL trial, revealed significant insights into biomarker associations with treatment response. Notably, high expression of Ki67 and CDK6, along with elevated ctDNA density at baseline, were correlated with shorter progression-free survival and overall survival. These findings illuminate potential avenues for understanding and overcoming resistance to CDK4/6 inhibitors, marking a significant step forward in personalized cancer treatment.

METSGain: Predictive Potential in Early Breast Cancer

Additionally, MEDSIR presented findings from the METSGain study, which focused on predicting the risk of distant recurrences and understanding metastatic processes in early breast cancer, analyzing data from the PHERGain trial. The study demonstrated that HER2DX risk-score measurement after treatment and tumor surgery can provide valuable insights into future distant metastases. Notably, patients with high-risk scores at surgery and less molecular changes after anti-HER2 therapy were more likely to develop metastasis, further highlighting the potential of HER2DX tool developed by REVEAL GENOMICS S.L. in guiding treatment decisions for HER2+ early breast cancer patients.

About Breast Cancer

Breast cancer is the most frequent cancer diagnosed in women with an estimated global incidence of over 2 million new cases annually and is a heterogeneous disease with multiple clinical presentations and outcomes. Risk factors include family history, advanced age, hormone exposure, alcohol consumption, or smoking. Early diagnosis, risk prediction, and ongoing research into treatments are crucial for improving the prognosis and quality of life for those affected by this disease.

On April 9, 2024 Rakovina Therapeutics Inc.), a biopharmaceutical company dedicated to improving the lives of cancer patients through the development of novel DNA-damage response inhibitor therapeutics, reported that members of the Company’s scientific team presented new data on the Company’s novel kt-3000 series at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting at the San Diego Convention Center (Press release, Rakovina Therapeutics, APR 9, 2024, View Source [SID1234641951]).

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In the presentation entitled, "Pharmacological Synthetic Lethality by Co-Inhibition of PARP and HDAC Enzymes" during yesterday’s Late Breaking Experimental and Molecular Therapeutics Research session at the conference, Rakovina discussed conceptual insights on how co-inhibition of these enzymes can eliminate cancer cells with an intact DNA repair machinery.

"We are very proud of our continued progress in our quest to find new treatments for cancer," said Rakovina Executive Chair Jeffrey Bacha. "The research was led by our President and Chief Science Officer Dr. Mads Daugaard, and we continue to be highly encouraged about the direction of our pre-clinical research."

"The combination of PARP and HDAC inhibition activity in one single drug candidate showed strong anti-tumor cell activity in DNA repair-proficient cells where single agent PARP inhibitors have limited effects", said Dr. Daugaard. "Our research continues to support the idea that the development of bifunctional PARP-HDAC inhibitors may provide a novel therapeutic opportunity for tumors with resistance to first-generation PARP inhibitors".

According to Bacha, first-generation PARP inhibitors have become an important standard-of-care in the treatment of several major solid tumors, including subsets of breast, lung and prostate cancers, generating nearly USD $3 billion in annual revenue. Resistance to PARP inhibitors develops over time so continued innovation is needed to meet the need for new and better treatments.

Dr. Daugaard said, "Lead candidates from our kt-3000 series dual-function PARP-HDAC inhibitors demonstrate the ability to overcome resistance to treatment and potentially treat cancers that would normally respond poorly to treatment with first-generation PARP inhibitors (such as Ewing Sarcoma, or any other DNA repair-proficient types of cancer). This novel approach not only addresses the unmet need, but also opens the door to potentially treat a wide range of cancers currently outside the scope of the first-generation PARP inhibitors.

Development of Rakovina Therapeutics’ kt-3000 series is supported, in part, by the St. Baldrick’s Foundation Martha’s BEST Grant for All, which is aimed at developing new treatments for Ewing sarcoma, an aggressive bone and soft tissue cancer in children and young adults.

Collaborators on this project include the Vancouver Prostate Centre, Vancouver, Canada; Rakovina Therapeutics, Vancouver Canada; the Department of Urologic Sciences, the Department of Pathology and Laboratory Medicine and the Department of Urologic Sciences, University of British Columbia, Vancouver, Canada.

The AACR (Free AACR Whitepaper) is celebrating its 115th year and expects over 21,000 attendees from around the world.

The Company recently announced a strategic evolution in its business model that places Rakovina at the forefront of artificial intelligence-driven (AI), precision research for cancer drug development. (See press release of March 27, 2024.)