On September 30, 2024 Akeso (9926. HK) reported that its internally developed PD-1/CTLA-4 bispecific antibody, cadonilimab, has received approval from the National Medical Products Administration (NMPA) for a new indication: cadonilimab in combination with fluoropyrimidine and platinum-based chemotherapy for first-line treatment of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (Press release, Akeso Biopharma, SEP 30, 2024, View Source [SID1234646953]). This is the second indication approval for cadonilimab in China, following its initial approval for marketing in June 2022.

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The approval of the new indication for cadonilimab combination therapy for first-line treatment of gastric/GEJ cancer is based on the COMPASSION-15/AK104-302 study. In the COMPASSION-15 study, the proportion of patients with PD-L1 CPS < 5 and PD-L1 CPS < 1 in the Intention-to-Treat (ITT) population reached 49.8% and 23%, respectively, which is significantly higher than the data disclosed in previous phase III studies of other immunotherapies for first-line treatment.

In November 2023, the interim analysis of the study achieved the primary endpoint of overall survival (OS). The results showed that the cadonilimab combination therapy significantly reduced the risk of death in advanced gastric cancer patients across all PD-L1 expression levels (including those with PD-L1 CPS ≥5 and <5), extending overall survival benefits and demonstrating notable advantages in objective response and long-term survival. Previous phase III trials of PD-1 inhibitors combined with chemotherapy showed limited or no clinical benefit for patients with low or negative PD-L1 expression.

The results of the COMPASSION-15 study were presented as an oral report at the 2024 AACR (Free AACR Whitepaper). In the ITT population, the median overall survival (mOS) for the cadonilimab regimen reached 15.0 months, compared to 10.8 months in the control group, extending overall survival by 4.2 months and reducing the risk of death by 38% (HR=0.62). In the PD-L1 CPS <5 group, the mOS for the cadonilimab regimen was 14.8 months, with a 30% reduction in the risk of death compared to the control group (11.1 months, HR=0.70). For the PD-L1 CPS ≥5 group, the mOS had not yet been reached, but the risk of death was reduced by 44% compared to the control group (10.6 months, HR=0.56).

COMPASSION-15’s principal investigator, Professor Ji Jiafu from Peking University Cancer Hospital, stated:

" The prognosis for advanced gastric cancer is poor. While currently approved immunotherapy options have improved efficacy compared to traditional chemotherapy, there remains significant potential for enhancement. The cadonilimab combination therapy has substantially increased the objective response rate and overall survival in the general population while reducing disease-related mortality. Remarkably, cadonilimab shows significant overall survival benefits not only in patients with high PD-L1 CPS expression but also in those with low or negative PD-L1 CPS expression.

The approval of cadonilimab as a first-line treatment effectively addresses the efficacy gap of PD-1/L1 monoclonal antibodies in patients with low or negative PD-L1 expression, providing a more comprehensive and effective immunotherapy option for advanced gastric cancer. This advancement benefits all patient populations and presents new opportunities for the global development of gastric cancer immunotherapy, carrying important clinical implications.

As a clinician, I am enthusiastic about the approval of cadonilimab for advanced gastric cancer. This innovative treatment will offer a superior and more comprehensive immunotherapy option for patients, and I look forward to its impact on optimizing the current clinical landscape for advanced gastric cancer."

COMPASSION-15’s principal investigator, Professor Shen Lin from Peking University Cancer Hospital, stated:

"We are delighted by the successful approval of cadonilimab combination therapy for the first-line treatment of advanced gastric cancer. This regimen offers significant advantages over current immunotherapy options in clinical practice, providing a superior choice not only for patients with high PD-L1 expression but also for those with low or negative PD-L1 expression, who previously lacked effective treatment options.

Cadonilimab addresses the limitations of single-target immunotherapy and exemplifies the synergistic mechanism of dual immune therapy with "anti-PD-1 + anti-CTLA-4," thereby filling an important clinical gap in the treatment of advanced gastric cancer. Beyond first-line approval, the phase III clinical study (AK109-301) of cadonilimab combined with pulocimab (AK109, VEGFR-2) for treating advanced gastric cancer that has progressed after PD-1/L1 inhibitor plus chemotherapy has been initiated. There is currently a lack of effective standard treatments for patients with acquired resistance to immunotherapy, and we eagerly anticipate that this new combination regimen will yield improved results in second-line therapy for these patients, ultimately providing clinicians with more effective tools for cancer treatment."

Dr. Xia Yu, Founder, Chairwoman, President, and Chief Executive Officer of Akeso Biopharma, stated:

"We thank all researchers, participants, and patients involved in this clinical study. Their collective efforts have led to the approval of cadonilimab combination therapy for first-line treatment of advanced gastric cancer, introducing a novel bispecific immune therapy combined with chemotherapy.

As immunotherapy evolves, global regulators and the medical community are reassessing the real-world benefits of PD-1 therapies across different PD-L1 expression levels in gastric and esophageal cancers.

Cadonilimab, a novel bispecific antibody targeting both PD-1 and CTLA-4, is supported by robust evidence demonstrating significant clinical benefits for the entire gastric cancer population. Differentiating from PD-1 monoclonal antibody combinations, cadonilimab also shows substantial advantages for patients with low or negative PD-L1 expression. Akeso will continue to explore the global clinical value of cadonilimab."

Gastric cancer is one of the most common malignant tumors worldwide. According to the International Agency for Research on Cancer (IARC) 2022 statistics, there are nearly one million new cases each year, making it the fifth most common cancer. China accounts for about half of these cases and deaths, with HER2-negative patients representing around 88%. For those ineligible for surgery or with metastatic gastric cancer (including gastroesophageal junction cancer), immunotherapy using PD-1/L1 monoclonal antibodies has shown success in first-line treatment, though survival benefits remain limited. Cadonilimab combination therapy is expected to provide a more effective treatment option.

On September 30, 2024 Regor Pharmaceuticals (USA) ("Regor") reported that it has entered into a definitive purchase agreement whereby Genentech, a member of the Roche Group, will acquire a portfolio of next-generation CDK inhibitors from Regor for the treatment of breast cancer (Press release, Regor Therapeutics, SEP 30, 2024, View Source [SID1234646951]).

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Under the terms of the agreement, Regor will receive an upfront cash payment of $850 million and is eligible to receive additional cash payments based on the achievement of certain predetermined development, regulatory and commercial milestones. Genentech will be responsible for clinical development, manufacturing and commercialization worldwide. Regor will continue to manage the two ongoing Phase 1 trials to their completion: Regor will also advance its other distinct assets, unrelated to this deal, in oncology, metabolic diseases and auto-immunity.

"Genentech is well-positioned to bring these novel therapeutics to their full potential to benefit patients with breast cancer around the world," said Xiayang Qiu, Ph.D., founder and CEO of Regor. " We are proud of the strong data we have generated to date. We look forward to bringing more innovative therapies to patients around the world."

The proposed transaction is expected to close in the fourth quarter of 2024. The closing of the proposed transaction is subject to the satisfaction of customary closing conditions.

BofA Securities, Inc. is acting as the exclusive financial advisor to Regor on this transaction, and Cohen, Tauber Spievack & Wagner PC and DLA Piper are its legal advisors.

On September 30, 2024 Photocure ASA (OSE: PHO), the Bladder Cancer Company, reported that its partner Asieris Pharmaceuticals (SSE: 688176) communicated that international multicenter Phase III clinical study data for its non-surgical treatment candidate Cevira (APL-1702) for cervical High-Grade Squamous Intraepithelial Lesion (HSIL) has been published by the 27th Chinese Society of Clinical Oncology (CSCO) Annual Meeting as a poster, focusing on the analysis of different age subgroups regarding the six-month pathological regression rate and HPV clearance rate (Press release, Asieris Pharmaceuticals, SEP 30, 2024, View Source [SID1234646948]).

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This Phase III clinical trial is a prospective, randomized, double blind, placebo controlled, multi-center clinical study, which has reached its primary efficacy endpoint and exhibited good safety.

Furthermore, the study results included the pathological regression rate (defined as the proportion of subjects with a pathological regression to CIN1 or normal tissue) at the 6th month across different age subgroups. Both the "≥20 and <30 years" subgroup and the "≥30 and <40 years" subgroup showed an increase of 15% to 20% in the pathological regression rate in the APL-1702 group compared to the placebo control group. No cervical cancer events were reported, suggesting a significant therapeutic potential of APL-1702 in the HSIL population aged 20 to 40 years.

Regarding HPV clearance rate, in the "≥20 and <30 years" age group, the APL-1702 group showed enhancements in the overall HPV clearance rate, HPV16-positive clearance rate, and HPV16/18-positive clearance rate compared to the placebo control group. The patients’ number in the "<20 years" and "≥40 years" age groups were limited, thus the results in these age groups require a validation study with a larger sample size. Overall, APL-1702 not only facilitates the regression from HSIL to LSIL but also demonstrates the ability to induce clearance of high-risk HPV infections.

On September 30, 2024 Aktis Oncology, a clinical-stage biotechnology company pioneering the discovery and development of novel targeted alpha radiopharmaceuticals to treat a broad range of solid tumors, reported the successful closing of an oversubscribed and upsized $175 million Series B financing (Press release, Aktis Oncology, SEP 30, 2024, View Source [SID1234646945]). The financing was led by RA Capital Management, and co-led by RTW Investments and Janus Henderson Investors. A select syndicate of additional new investors joined the financing, including funds and accounts advised by T. Rowe Price Associates, Inc., Avidity Partners, and an undisclosed life sciences-focused investment fund. All existing institutional investors participated, as well as existing strategic investors Bristol Myers Squibb, Eli Lilly and Company, and MRL Ventures Fund, the therapeutics-focused corporate venture fund of Merck & Co., Inc.

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Aktis Oncology also announced that three abstracts, including one oral presentation, have been accepted for presentation at the upcoming EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain, October 23-25, 2024.

"The overwhelming support from high caliber investors underscores the progress we have made on our pipeline, platform, and supply chain capabilities, exemplified by the significant opportunity for AKY-1189, our first-in-class miniprotein alpha radioconjugate targeting Nectin-4 in development for several tumor types," said Matthew Roden, PhD, President and Chief Executive Officer of Aktis Oncology. "With over $300 million in cash, we are well-positioned to prosecute several opportunities to expand the benefit of this exciting modality into new patient populations."

In conjunction with the financing, Andrew Levin, MD, PhD, Partner and Managing Director at RA Capital Management, will join the Aktis Oncology Board of Directors. Lauren Lee, PhD, from RTW Investments, and Vish Sridharan, MD, from Janus Henderson Investors, will join as Observers to the Board of Directors.

"Aktis has leveraged its unique technology platform, experienced team, robust supply chain and radiopharmaceutical development capabilities to generate a promising and differentiated pipeline of next-generation radiopharmaceuticals," said Andrew Levin, MD, PhD, Partner and Managing Director at RA Capital Management. "We are pleased to support Aktis through the next stage of its growth as it seeks to bring new options to patients with cancer."

On September 30, 2024 BioAI, an emerging biotech company applying multimodal artificial intelligence (AI) to novel biomarker discovery, development, and diagnostics, reported a strategic partnership with Arbele, a biopharmaceutical company dedicated to developing novel immunotherapeutic platforms for gastrointestinal cancers (Press release, ARBELE, SEP 30, 2024, View Source [SID1234646944]).

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The collaboration aims to leverage BioAI’s PredictX platform to develop AI-based models using Arbele’s clinical trial data, with a focus on colorectal cancer (CRC) biomarker screening. The goal is to create a companion diagnostic test for Arbele’s drug assets, enhancing patient selection through advanced AI technology.

"By joining forces 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."

Arbele’s CEO & Founder, Dr. John Luk, commented, "BioAI’s machine learning capabilities offer a transformative approach to biomarker identification and patient stratification. This collaboration is a critical step in improving outcomes for patients with high mortality cancers."

The initial phase of the partnership will focus on developing a prototype machine learning classifier model for quantifying CDH17 expression patterns in CRC samples, using a combination of H&E (hematoxylin and eosin) and IHC (immunohistochemistry) stained images. This initiative aims to standardize and improve the pathologic assessment of treatment response biomarkers to facilitate more effective patient selection for Arbele’s specific therapeutic programs. Both companies expect that this collaboration will pave the way for future advances in precision medicine, ultimately benefiting patients with gastrointestinal cancers.