On October 12, 2023 Asieris Pharmaceuticals (Stock Code: 688176.SH), a global biopharma company specializing in discovering, developing and commercializing innovative drugs for the treatment of genitourinary tumors and other related diseases, reported that it has unveiled its phase III clinical trial data for APL-1706 (Hexvix), an imaging drug used for the diagnosis or surgery of bladder cancer, at the 43rd Congress of the Société Internationale d’Urologie (SIU) in 2023 (Press release, Asieris Pharmaceuticals, OCT 12, 2023, View Source [SID1234635904]). The study confirmed that, in the Chinese patient, APL-1706 in combination with blue light cystoscopy (BLC) outperformed white light cystoscopy (WLC) in the detection of bladder cancer, particularly in cases of carcinoma in situ (CIS), and exhibited good tolerability.

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The study included a total of 158 patients, with 37 patients in the training cases group. Six patients were randomly assigned to the standard WLC control group, and one patient dropped out, leaving 114 patients in the full analysis set (FAS). Among the 97 patients diagnosed with Ta, T1, and CIS (mFAS), compared to standard WLC, a total of 42 patients (43.3%) detected one or more additional bladder cancer lesions through the combination of APL-1706 and blue light cystoscopy (p<0.0001). Among the 114 patients, 13 patients (11.4% ,13/114) had CIS lesions, and among these, 11 patients (84.6%, 11/13) had additional CIS lesions detected under BLC that were not found under WLC. The detection rates for PUNLMP, CIS, Ta, T1, and T2-T4 tumor lesions in the BLC group were NA, 94.7%, 100%, 98.2%, and 100%, respectively, while in the WLC group, they were NA, 42.1%, 76.1%, 91.2%, and 100%, respectively. The false positive rates for BLC and WLC were 23.2% and 16.0%, respectively. A total of 95 patients reported 200 adverse events, all of which were mild to moderate, with 95.5% of them unrelated to APL-1706. There were no serious adverse events reported.

Dr. Linda Wu, Chief Development Officer of Asieris Pharmaceuticals, said, "APL-1706 is currently the only approved optical imaging for assisting in the diagnosis and surgery of bladder cancer worldwide. The data presented at the SIU conference further validates the tremendous clinical value of APL-1706. We believe that this innovative drug will bring significant benefits to bladder cancer patients in the local market. We will actively advance the related regulatory submissions in China, expediting its market entry to benefit more patients as soon as possible."

In January 2021, Asieris entered into a license agreement with Photocure ASA (Photocure, OSE:PHO), a bladder cancer specialty company based in Oslo, Norway, and obtained the exclusive registration and commercialization rights of Hexvix in mainland China and Taiwan.

On October 12, 2023 Avenge Bio, Inc. ("Avenge"), a clinical stage, oncology-focused biotechnology company developing the LOCOcyte Immunotherapy platform for the precision administration of potent immune effector molecules to treat solid tumors, reported participation in the upcoming investor conference (Press release, Avenge Bio, OCT 12, 2023, View Source [SID1234635903]).

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3rd Annual Needham Private Biotech Company Virtual 1×1 Forum
Date & Time: October 17-18, 2023

In September 2023, Avenge Bio received FDA Fast Track designation for AVB-001. AVB-001 is an encapsulated cell product engineered to produce native human interleukin-2 (hIL-2) and is delivered intraperitoneally (IP) to patients. Avenge is currently enrolling patients in a First-in-Human, Phase 1/2, multicenter clinical trial (NCT05538624) designed to evaluate the safety and efficacy of AVB-001. The Company has advanced through multiple dose levels in a dose escalation cohort and expects to initiate a Phase 2 dose expansion trial in 1H 2024.

On October 12, 2023 Nested Therapeutics, a biotechnology company pioneering a next-generation precision medicine platform to address hard-to-treat cancers, reported the first preclinical data from its lead candidate, NST-628, a mechanistically novel non-degrading molecular glue that targets multiple nodes in the RAS/MAPK pathway, outlined in three poster presentations at the 2023 AACR (Free AACR Whitepaper)-NCI-EORTC International Conference taking place in Boston, Massachusetts from October 11-15, 2023 (Press release, Nested Therapeutics, OCT 12, 2023, View Source [SID1234635902]).

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NST-628 outperformed other MAPK-targeted compounds administered as either single agents or combinations in anti-tumor activity and tolerability. Additionally, NST-628 effectively crossed the blood-brain barrier, suggesting a potential advantage for the treatment of brain metastases and primary CNS malignancies with MAPK pathway alterations.

"Taken together, these superior preclinical data suggest that NST-628 could offer a potential first-in-class treatment in the current RAS/MAPK inhibitor space, supporting its advancement into first-in-human clinical trials," said Darrin Miles, Chief Executive Officer of Nested Therapeutics. "We understand the need to bring more effective treatment options that have the ability to overcome the intrinsic mechanisms that tumor cells evolve to become resistant to cancer therapies, and we look forward to initiating our Phase 1 study in patients in the first half of 2024."

NST-628 is being developed through a robust biophysical and cellular characterization to leverage proprietary structural insights of how signaling complexes form and function in cancer. The compound acts through a defined mechanism of action that could address common pitfalls of other MAPK-targeted compounds, which remain unable to circumvent the risk of intrinsic resistance via signaling pathway reactivation.

Key takeaways from the posters are as follows:

NST-628 is a novel molecular glue that inhibits signaling and pathway reactivation in oncogenic RAS-MAPK cancers (Abstract Number: A086)

NST-628 bound to CRAF-MEK, BRAF-MEK, ARAF-MEK complexes were structurally characterized using x-ray crystallography and cryogenic electron microscopy (cryo-EM). Increased stabilization of the CRAF-MEK complex by NST-628 was observed and may contribute to the decreased pathway reactivation in specific biomarker-driven tumors.
NST-628 is a potent, best-in-class MAPK pathway molecular glue that inhibits RAS- and RAF-driven cancers (Abstract Number: A088)

NST-628 demonstrated strong efficacy and tolerability across multiple tumor types with RAS-MAPK alterations, including melanoma, lung, and pancreatic animal models.
The predicted effective human half-life is amenable to daily dosing in the clinic, supporting best-in-class potential for NST-628.
NST-628 is a potent, fully brain-penetrant, RAS/MAPK pathway molecular glue inhibitor with efficacy in CNS tumor models (Abstract Number: A089)

Currently approved inhibitors of the RAS-MAPK pathway have limited CNS exposure, and NST-628 demonstrates full CNS permeability far higher than trametinib or VS-6766.
NST-628 leads to dose-dependent inhibition of the MAPK pathway in murine brain tissue, along with tumor regressions observed with a daily dosing regimen.
Nested Therapeutics plans to submit an IND for NST-628 following completion of ongoing preclinical and IND-enabling studies, to support first-in-human studies to start in the first half of 2024.

About DeCRYPTion Platform

Nested Therapeutics’ DeCRYPTion Platform is a purpose-built, insightful drug discovery platform that enables Nested to identify new, overlooked areas of opportunity in the form of high value targets and design therapeutics for a perfect fit. The platform includes three critical components: (1) mapping mutational clusters onto the structural proteome, (2) identifying druggable pockets and cancer-driving mechanisms, and (3) designing novel drugs optimized for the druggable pocket.

On October 12, 2023 Aadi Bioscience, Inc. (NASDAQ: AADI), a biopharmaceutical company focused on developing and commercializing precision therapies for patients with mTOR pathway alterations, reported details of four poster presentations at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), taking place October 11-15, 2023, in Boston, MA (Press release, Aadi Bioscience, OCT 12, 2023, View Source [SID1234635901]).

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Abstracts and poster presentation details are below:

Title: "Inactivating TSC1 and TSC2 alterations, co-mutations, and genomic instability in advanced cancers: Analysis of a real-world (RW) patient population using the Foundation Medicine genomic database"
Poster Number: C019
Session Title: Poster Session C
Date/Time: Saturday, October 14, 2023, 12:30 pm-4:00 pm EDT
Authors: David J. Kwiatkowski, MD, PhD; Norma A. Palma, PhD; Willis H. Navarro, MD; Gopa Iyer, MD

Abstract highlights:

To appreciate the potential for TSC1 and TSC2 as therapeutic biomarkers, TSC1 and TSC2 mutational data from an RW genomic database were analyzed.
Next-generation sequencing data from Foundation Medicine’s genomic database of patients primarily with advanced cancer were analyzed using the FoundationInsights web-based platform.
In a large RW database of patients with advanced cancer, inactivating TSC1 and TSC2 variants occurred in 1.9% of patients. These occurred across common tumor types at rates as high as 8.6% (urinary bladder tumors).
These observations suggest cancers with TSC1 and/or TSC2 alterations may be candidates for targeted therapy.
Title: "Real-world (RW) characterization and frequency of TSC1 and/or TSC2 alterations collected from tumor tissue and liquid biopsies from the Tempus genomic database in patients with advanced cancer" Poster Number: B003
Session Title: Poster Session B
Date/Time: Friday, October 13, 2023, 12:30 pm-4:00 pm EDT
Authors: David J. Kwiatkowski, MD, PhD; Norma A. Palma, PhD; Willis H. Navarro, MD; Gopa Iyer, MD

Abstract highlights:

PRECISION1 will assess the clinical benefit of nab-sirolimus in patients with cancer with inactivating TSC1 or TSC2 alterations.
To appreciate the potential for TSC1 and/or TSC2 targeted therapy, TSC1 and TSC2 alterations across a large RW patient population with advanced cancer using data from tissue and liquid biopsies were analyzed.
In a large (N=154,965) NGS database of patients with cancer, inactivating TSC1 and/or TSC2 variants occurred in about 1.7% of patients overall and were frequently identified in commonly occurring cancers.
The frequency of TSC1 and/or TSC2 alterations and tumor types were generally consistent between tumor tissue samples and liquid biopsies.
Consistency between primary vs metastatic samples suggests TSC1 and TSC2 alterations may not be acquired, although samples were not longitudinal.
Title: "Evaluation of nab-sirolimus in combination with PI3K pathway inhibitors to overcome PI3K/mTOR resistance in PI3K-mutant breast cancer cell lines" Poster Number: A117
Session Title: Poster Session A
Date/Time: Thursday, October 12, 2023, 12:30 pm-4:00 pm EDT
Authors: Sean Wallace, PhD; Khine Nyein Myint, PhD; Shihe Hou, PhD; Maria Zalath, BA; Andrew Kwon, PhD; Brian McMorran, PhD; Igor Vivanco, PhD

Abstract highlights:

The PI3K-AKT-mTOR pathway is frequently activated in many cancer types and plays a central role in tumorigenesis. However, clinical use of therapies targeting this pathway is limited by compensatory vertical and horizontal feedback activation loops, which limit antitumor efficacy and lead to drug resistance.
Combination therapy strategies employing simultaneous inhibition of multiple PI3K-AKT-mTOR pathway elements may overcome these resistance mechanisms and improve antitumor activity. In these studies, we analyzed the effects of nab-sirolimus combinations in PI3K-mutant breast cancer (BrCa) cells.
The antitumor effects of PI3K and AKT inhibitors were enhanced by the addition of the novel mTOR inhibitor nab-sirolimus. The improved effectiveness of the PI3K and mTOR inhibitor combination was due to the reciprocal overcoming of resistance mechanisms induced by single agent treatment.
These data potentially support a vertical PI3K pathway inhibition strategy using nab-sirolimus and PI3K/AKT inhibitors in PIK3CA-mutated BrCa, regardless of hormone receptor status.
An encore presentation titled, "Phase 2, Multicenter, Open-label Basket Trial of nab-Sirolimus for Malignant Solid Tumors Harboring Pathogenic Inactivating Alterations in TSC1 and TSC2 (PRECISION1)" will also be presented during the late breaking session on Friday, October 13, 2023.

More information can be found on the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) meeting website.

On October 12, 2023 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a commercial stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases, reported the closing of an exclusive license agreement with Guangzhou Gloria Biosciences Co., Ltd. (GloriaBio) and an associated investor for the development of motixafortide across all indications in Asia (Press release, BioLineRx, OCT 12, 2023, View Source [SID1234635900]). Motixafortide is a novel, high-affinity CXCR4 inhibitor that received approval for its first indication in September 2023 by the U.S. Food and Drug Administration (FDA) for stem cell mobilization (SCM) in autologous stem cell transplantation (ASCT) in patients with multiple myeloma. Motixafortide is also being studied for other potential uses in oncologic and hematologic diseases.

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The license agreement provides for a $15 million upfront payment (which was received at closing), up to $50 million in potential development and regulatory milestones in China and Japan, and up to $200 million in potential commercial milestones based on defined sales targets. BioLineRx is also eligible to receive tiered double-digit royalties on net sales.

In addition, the transaction included an equity investment of $14.6 million in BioLineRx through the purchase of newly issued American Depositary Shares (ADSs) at a price of $2.136 per ADS in a private placement. No warrants were issued in the transaction. Along with the investment, the purchaser received the right to appoint one representative to the BioLineRx Board of Directors.

Collaboration Details

Under the terms of the license agreement, GloriaBio will be responsible for development and commercialization of motixafortide in Asia initially in SCM. With the recent FDA approval of APHEXDA for this indication, GloriaBio plans to initiate a bridging study to support potential approval and commercialization of motixafortide in the licensed territories in SCM for ASCT in patients with multiple myeloma.

In addition, GloriaBio plans to initiate a Phase 2/3 first-line pancreatic cancer clinical trial evaluating motixafortide in combination with PD-1 inhibitor *zimberelimab and standard of care combination chemotherapy. BioLineRx has been developing motixafortide in combination with PD-1 inhibitors and standard of care combination chemotherapies in pancreatic cancer, and recently announced the initiation of a randomized Phase 2 clinical trial sponsored by Columbia University in first-line metastatic pancreatic cancer based on promising preliminary data from a single-arm pilot phase reported on September 29 at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Special Conference on Pancreatic Cancer.

"We are tremendously pleased by the swift closing of this significant licensing agreement for the Asian market, which brings substantial benefits to BioLineRx, and ultimately, to patients, including the advancement of our two leading development programs," said Philip Serlin, Chief Executive Officer of BioLineRx Ltd. "Given GloriaBio’s expertise and track record in the development and commercialization of cancer immunotherapies in China, we believe GloriaBio is well suited to further develop motixafortide in Asia. The combined initial investment of nearly $30 million through the upfront payment and equity investment demonstrates a clear commitment to the motixafortide programs in stem cell mobilization and pancreatic cancer in Asia, and provides us with additional capital to continue our aggressive launch plans in the U.S."

"We are very pleased to enter into this strategic partnership with BioLineRx and are committed to the development and commercialization of motixafortide in Asia, which we believe will bring additional value to GloriaBio’s portfolio via clear synergies with zimberelimab," said Jiman Zhu, Founder of GloriaBio. "There are very significant unmet patient needs in pancreatic cancer in Asia, especially in China. We are excited to see the encouraging clinical data of motixafortide in combination with PD-1 inhibitors and chemotherapy in pancreatic cancer and look forward to initiating a Phase 2/3 randomized trial in a first-line pancreatic cancer, as well as investigating additional indications for motixafortide in Asia."

MSQ Ventures served as advisor to BioLineRx on this transaction.

About Pancreatic Cancer in Asia
At nearly 240,000 reported cases in 2022, it is estimated that Asia had the largest number of pancreatic cancer cases globally (496,000 estimated cases worldwide). In China alone, the number of pancreatic cancer cases in 2020 reached approximately 125,000, with a 5-year survival rate of just 7.2%.

About Multiple Myeloma and Autologous Stem Cell Transplantation in Asia
Multiple myeloma is an incurable blood cancer that affects some white blood cells called plasma cells, which are found in the bone marrow. When damaged, these plasma cells rapidly spread and replace normal cells in the bone marrow.
In 2022, it is estimated that Asia had over 51,000 reported cases of multiple myeloma (MM), the largest number of MM cases globally. New cases of MM reached over 20,000 in Greater China in 2018, and MM incidence is predicted to increase at an annual growth rate of 2.9%.

Autologous stem cell transplantation (ASCT) can be an important treatment paradigm for a number of blood cancers, including multiple myeloma. In China, ASCTs are included in medical insurance reimbursement, and in 2019, the total number of ASCTs in China reached more than 10,000 for the first time (for comparative purposes, as many as 14,000 ASCTs are performed each year in the U.S.).

*About Zimberelimab (YuTuo)
Zimberelimab is a fully human anti-PD-1 monoclonal antibody. GloriaBio is developing and commercializing zimberelimab in Greater China, including mainland China, Hong Kong, Macao and Taiwan, where zimberelimab is approved for relapsed or refractory classical Hodgkin’s lymphoma and recurrent or metastatic cervical cancer. Arcus Biosciences, and development partner Gilead Sciences, have the exclusive rights to develop and commercialize zimberelimab throughout the world except in Greater China and certain territories.