On October 9, 2024 Arbele, a leading innovator in biopharmaceutical & biotechnology focused on targeting cadherin-17 (CDH17), reported strategic collaborations in precision oncology using artificial intelligence (AI) to advance targeted immunotherapeutics of bispecific T-cell engagers (TCEs) and antibody-drug conjugates (ADCs) (Press release, ARBELE, OCT 9, 2024, View Source [SID1234647113]). These partnerships, aimed at advancing the quantification and prognostic prediction of CDH17 expression in tumor tissue and the surrounding tumor immune microenvironment, are expected to accelerate the development of precise companion diagnostics and effective clinical trials for the treatment of advanced cancer patients.

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Collaboration with BioAI: Development of IHC-Based Quantification Algorithm

Arbele enters a strategic alliance with BioAI Health to develop a prototype of an immunohistochemistry (IHC)-based quantification algorithm. Leveraging the PredictX platform to develop AI-based models using Arbele’s clinical trial data on colorectal cancer (CRC) biomarker screening, we join force to establish a gold standard companion diagnostic test for anti-CDH17 therapies for patient selection and prediction of clinical outcomes.

"By partnering with Arbele, we are excited to apply our novel AI platform and expertise to accelerate the development of innovative treatment options for gastrointestinal cancers," said Thomas Colarusso, CEO of BioAI. "This partnership underscores our commitment to revolutionizing personalized medicine through cutting-edge machine learning."

"BioAI’s machine learning capabilities offer a transformative approach to biomarker identification and patient stratification through predicting CDH17 expression and its spatial interaction with immune cells in tumor microenvironment," said Dr John Luk, CEO of Arbele. "This collaboration is a critical step in guiding us the uses of the right treatment modalities and/or therapeutic regimens, thereby improving outcomes for patients with high mortality cancers."

Collaboration with Chime Biologics: Accelerated CMC Process Development of novel ADC and TCE

Arbele has entered a strategic alliance with Chime Biologics to accelerate chemistry, manufacturing and control (CMC) process development of the novel designs of ADCs and TCEs. The partnership supports multiple pipelines of about 10 first-in-class and best-in-class immunotherapeutics, including monoclonal, bispecific/biparatopic and TriAx antibodies within the coming 3 years. The collaboration will ensure Arbele continues to have at least 1-2 new molecular entities (NMEs) successfully filing for investigational new drug (IND) application and entering clinical studies in the next 5 years without any technical and supply-chain interruptions. The first deliverable will be anti-CDH17 ADC (ARB102A), for IND submission in early 2025.

"Chime Biologics has partnered Arbele for several years, with our advanced biologics development supporting key milestones such as previous IND filings for multinational clinical trials," said Dr. Jimmy Wei, President of Chime Biologics. "We adopt the Quality-by-Design (QbD) strategy for process development to yield optimal outcomes cost-effectively, delivering innovative immunotherapeutics to enhance the global accessibility of these treatments."

On October 9, 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 it will present four posters with clinical and preclinical data from RVU120 (CDK8/19 inhibitor), RVU305 (MTA-cooperative PRMT5 inhibitor), WRN and novel synthetic lethality programs at the 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium (ENA), October 23-25, Barcelona, Spain (Press release, Ryvu Therapeutics, OCT 9, 2024, View Source [SID1234647114]).

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"We are thrilled to showcase our latest advancements on RVU120, RVU305, and other synthetic lethality projects at the 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium this year. The strong preclinical data from our PRMT5 synthetic lethality program is highly encouraging as we target IND/CTA filing and continue to advance our project toward clinical studies." – said Krzysztof Brzózka, Ph.D., Chief Scientific Officer.

Poster highlights:

Abstract Title: Discovery of novel MTA-cooperative PRMT5 inhibitors as targeted therapeutics for MTAP-deleted cancers
Abstract Number: ENA24-0205
Session date and time: Wednesday, October 23 (12:00-19:00 CEST)

Ryvu has developed a potentially best-in-class MTA-cooperative PRMT5 inhibitor, RVU305, demonstrating favorable drug-like properties and effective PRMT5 inhibition dependent on MTA binding. Structure-based optimization has resulted in a compound exerting selective efficacy in MTAP-deleted cell lines and a DMPK profile suitable for oral administration. RVU305 exhibits robust antiproliferative activity in MTAP-null cancer models, with a favorable safety margin in MTAP wild-type cells. Comparative studies against other clinical-stage PRMT5 inhibitors confirmed RVU305’s favorable antitumor activity in vitro and in vivo. Overall, the findings highlight the potential of RVU305 as a promising therapeutic option for patients with MTAP-deleted cancers.

Abstract Title: Discovery of WRN inhibitors as targeted therapy in the treatment of microsatellite unstable (MSI-H) tumors
Number: ENA24-0364
Session date and time: Wednesday, October 23 (12:00-19:00 CEST)

Ryvu is developing a series of potent and selective WRN helicase inhibitors that demonstrate pronounced efficacy in tumors with high microsatellite instability (MSI-H). These compounds show nanomolar potency in viability assays in MSI-H cell lines, with excellent selectivity over microsatellite-stable (MSS) cells. In in vivo studies, RVU305 strongly suppressed tumor growth in an MSI-H model (SW48) while not impacting the MSS model (SW620). Additionally, the compounds exhibit favorable pharmacokinetics, achieving optimal exposure and target engagement, further enhancing their therapeutic potential in MSI-H cancers.

Abstract Title: Exploring synthetic lethality and novel drug combinations in patient-derived cells
Poster Number: ENA24-0395
Session date and time: Wednesday, October 23 (12:00-19:00 CEST)

Ryvu has developed a proprietary platform, ONCO Prime, to discover novel synthetic lethal (SL) inhibitors targeting key oncogenic drivers such as KRAS and other mutations. Initial data are presented in colorectal cancer (CRC), but the platform has the potential to discover novel SL targets across all tumor types. ONCO Prime uses human intestinal stem cell (hISC)-derived cancer model cells, patient-derived xenografts (PDXs), and clinical samples to conduct genomic and functional analyses. By integrating CRISPR/Cas9 technology and machine learning, Ryvu generated isogenic cancer models, performed high-throughput screenings, and validated the findings through transcriptomic profiling of clinically relevant samples. This approach enabled the identification of essential and tumor suppressor genes critical for CRC and other cancers, focusing on SL targets specific to transformed cells.

Abstract Title: Phase I/II trial of RVU120, a CDK8/CDK19 inhibitor in patients with relapsed/refractory metastatic or advanced solid tumors
Number: 34
Session date and time: Wednesday, October 23 (12:00-19:00 CEST)

RVU120 is being tested in patients with solid tumors in an ongoing Phase I/II clinical trial, AMNYS-51. RVU120 has demonstrated a manageable safety profile across multiple dose levels and dosing schedules in patients with advanced or metastatic solid tumors. No dose-limiting toxicities (DLTs) were observed, and most treatment-emergent adverse events (TEAEs) were mild to moderate, with nausea and vomiting being the most common. Stable disease (SD) was achieved in multiple patients, with tumor size reductions in three patients with adenoid cystic carcinoma (AdCC). The recommended phase 2 dose (RP2D) for the QOD schedule was identified as 250 mg, with dose escalation continuing for the QD schedule. These promising safety and preliminary efficacy results support further clinical investigation of RVU120.

Investor Event:
Ryvu Therapeutics will host a webinar to discuss new data from our latest poster presentations. The date and time of the webinar will be announced soon.

On October 9, 2024 Nanjing Leads Biolabs Co., Ltd. ("Leads Biolabs") reported that Center for Drug Evaluation (CDE) of National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation to LBL-024, an anti-PD-L1/4-1BB bispecific antibody independently developed by Leads Biolabs with global intellectual property rights, for the treatment of the patients with advanced extrapulmonary neuroendocrine carcinoma (EP-NEC) who have progressed after receiving two or more lines of chemotherapy (Press release, Nanjing Leads Biolabs, OCT 9, 2024, View Source [SID1234647115]). The Breakthrough Therapy Designation awarded to LBL-024 stems from its remarkable clinical efficacy and safety profile in patients with advanced EP-NEC who failed in second-line and above chemotherapy. The current clinical data demonstrate that LBL-024 monotherapy has more than doubled both the Objective Response Rate (ORR) and Overall Survival (OS) compared to existing treatments for this disease.

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Breakthrough Therapy refers to innovative or improved drugs that treat life-threatening conditions or significantly impact quality of life, where no effective treatment exist, or there is sufficient evidence that the therapy offers clear advantages over existing treatment options. In July 2012, the U.S. Food and Drug Administration (FDA) pioneered the "Breakthrough Therapy" review process, complementing fast track, accelerated approval, and priority review mechanisms. By accelerating the approval process and fostering closer collaboration, Breakthrough Therapy Designation facilitates faster development and market access for drugs with significant clinical potential. Historically, FDA data suggests that Breakthrough Therapy Designation can reduce time-to-market by approximately 2.5 years on average.

In July 2020, CDE officially introduced the Breakthrough Therapy Designation concept in China. Products granted Breakthrough Therapy Designation status will receive closer guidance and various forms of support to ensure that patients are provided with new treatment options as soon as possible.

Dr. Charles Cai, Chief Medical Officer of Leads Biolabs, said "According to historical data from the China Drug Review Annual Report, only a few products are eligible for Breakthrough Therapy Designation, and even fewer have been approved. The designation for LBL-024 is another proof of the robust R&D capabilities of Leads Biolabs, and it is also a major victory for Leads Biolabs’ insistence on focusing on the first-in-class product R&D strategy for the global market. Leads Biolabs will vigorously pursue the global clinical development of LBL-024, with the anticipation of offering more effective treatment options for patients with EP-NEC at the earliest opportunity."

Dr. Xiaoqiang Kang, founder, chairman and CEO of Leads Biolabs, said "The Breakthrough Therapy granted by the CDE prioritizes candidates that demonstrate exceptional clinical data, differentiated targets, and therapies with a high degree of efficacy certainty. This Designation represents the highest threshold and most prestigious qualification within China’s pharmaceutical regulatory system, functioning as a crucial benchmark for uncovering valuable new drug projects. Leads Biolabs has consistently embraced differentiated innovation, and we eagerly anticipate the timely market introduction of LBL-024 as a novel immunotherapy, following the groundbreaking successes of anti-PD-1/PD-L1, CTLA-4, and LAG-3."

About LBL-024

LBL-024 is a tetravalent bispecific antibody that simultaneously targets PD-L1 and 4-1BB, serving dual functions: blocking the immunosuppressive PD-1/PD-L1 pathway, and selectively co-stimulating 4-1BB in the tumor microenvironment to enhance immune responses. The dual functions of LBL-024—lifting PD-1/PD-L1 immune inhibition and intensifying 4-1BB modulated T cell activation—synergistically enhance the anti-tumor immune response.

About EP-NEC

Neuroendocrine carcinoma (NEC) is a class of poorly differentiated, high-grade neuroendocrine neoplasms (NENs), which originate in the diffuse neuroendocrine cell system and can occur in many different sites. NEC can be categorized into pulmonary NEC and EP-NEC. EP-NEC exhibits similar highly aggressive and metastatic characteristics to small cell lung cancer (SCLC). Most patients are diagnosed at a later stage or already have distant metastases, resulting in rapid disease progression and a poor prognosis.

Currently, the primary first-line treatment for advanced EP-NEC involves platinum-based chemotherapy, achieving an overall response rate (ORR) of approximately 30% to 50%, with a median overall survival (mOS) of only approximately one year. Treatment options for advanced EP-NEC are limited, and there are no standard treatment strategies for patients who progress beyond second-line chemotherapy. These underscore the urgency to develop novel therapeutic approaches.

On October 8, 2024 Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX), a clinical-stage pharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors, reported that it intends to offer and sell, subject to market and other conditions, $400.0 million of shares of its common stock in a proposed underwritten public offering (Press release, Crinetics Pharmaceuticals, OCT 8, 2024, View Source [SID1234647083]). In addition, Crinetics intends to grant the underwriters a 30-day option to purchase up to an additional $60.0 million of shares of common stock. All of the shares to be sold in the proposed offering are to be sold by Crinetics. There can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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Crinetics intends to use the net proceeds from the proposed offering, together with its existing cash, cash equivalents and investment securities, to fund research and development of its clinical-stage product candidates, other research programs, pre-commercialization activities and other general corporate purposes, which may include, among other things, capital expenditures or working capital. Crinetics may also use a portion of the remaining net proceeds, together with its existing cash, cash equivalents and investment securities, to in-license, acquire, or invest in complementary businesses, technologies, products or assets; however, it has no current commitments or obligations to do so.

Leerink Partners and Morgan Stanley are acting as joint bookrunning managers for the proposed offering.

The securities described above are being offered by Crinetics pursuant to a shelf registration statement that became automatically effective upon its filing with the Securities and Exchange Commission (SEC). The proposed offering may be made only by means of a prospectus supplement and accompanying prospectus. A preliminary prospectus supplement and accompanying prospectus relating to this offering will be filed with the SEC. When available, copies of the preliminary prospectus supplement and the accompanying prospectus relating to this offering may be obtained from: Leerink Partners LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, by telephone at (800) 808-7525, ext. 6105, or by email at [email protected]; or Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, New York 10014, by email at [email protected]. Electronic copies of the preliminary prospectus supplement and accompanying prospectus will also be available on the website of the SEC at www.sec.gov.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction.

On October 8, 2024 Bayer and MOMA Therapeutics, Inc., a clinical-stage biopharmaceutical company discovering and developing a new generation of precision therapeutics, reported that they have entered into a collaboration, under an option and exclusive license agreement, to develop and commercialize a small molecule oncology program based on MOMA’s proprietary KNOMATIC platform (Press release, Bayer, OCT 8, 2024, View Source [SID1234647099]). Under the agreement, Bayer will be responsible for completing further preclinical, development and commercial activities.

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"We are excited to partner with MOMA Therapeutics to explore the untapped potential of highly dynamic proteins in oncology," said Juergen Eckhardt, M.D., Head of Business Development and Licensing at Bayer’s Pharmaceuticals Division. "This collaboration reinforces Bayer’s commitment to precision medicine while enhancing our ability to address significant unmet medical needs in cancer treatment. By leveraging MOMA’s cutting-edge technologies and our expertise, we aim to accelerate the development of innovative therapies that can make a meaningful difference in patients’ lives."

Under the agreement, Bayer will gain access to the program itself along with results generated via MOMA’s KNOMATIC platform. This platform integrates deep structural insights with advanced hit-finding technologies and computation-enabled lead optimization to accelerate the discovery of therapeutics that effectively target highly dynamic proteins. Dynamic proteins represent an emerging class of therapeutic targets that can play critical roles in disease progression. Targeting these proteins via a small molecule approach offers a largely untapped means of developing innovative cancer therapies.

"We are thrilled to be partnering with Bayer to drug this disease-relevant target," said Asit Parikh, M.D., Ph.D., chief executive officer of MOMA. "Following our recent announcement highlighting the advancement of our wholly owned Pol theta and Werner programs, Bayer’s interest in this collaboration further highlights the power of our KNOMATIC platform and MOMA’s openness to creating win-win partnerships."

Under the terms of the agreement, MOMA will receive an upfront payment and collaboration fee and is eligible to receive additional payments based on the achievement of certain near-term discovery, development and commercial milestones, as well as tiered royalties on net sales.

Financial terms of the collaboration were not disclosed.