On September 30, 2024 Alphamab Oncology (stock code: 9966 HK) reported that Jiangsu Alphamab Biopharmaceuticals Co., Ltd. ("Alphamab"), a wholly-owned subsidiary of Alphamab Oncology ("the Company"), entered into a licensing agreement (the "Licensing Agreement") on anti-HER2 bispecific antibody-drug conjugate (ADC) JSKN003 with JMT-Bio Technology Co., Ltd. ("JMT-Bio"), a wholly-owned subsidiary of CSPC Pharmaceutical Group Co., Ltd. ("CSPC") (stock code: 1093.HK) (Press release, Alphamab, SEP 30, 2024, View Source [SID1234653663]).

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According to the terms of the Licensing Agreement, JMT-Bio will obtain the exclusive license and sublicense rights to develop, sell, offer for sale and commercialize JSKN003, for the treatment of tumor-related indications (the "Field") in mainland China (excluding Hong Kong, Macau or Taiwan) (the "Territory") and become the sole marketing authorization holder for JSKN003 for the Field in the Territory. JMT-Bio shall bear at its own costs and expenses for the clinical development activities under the Licensing Agreement. Alphamab retains the sole right to supply JSKN003 for any purpose within or outside the Territory.

According to the Licensing Agreement, the Company is entitled to receive upfront payment and milestone payments of up to RMB 3.08 billion in total, including an upfront payment of RMB 400 million, a development milestone payment of RMB 300 million related to enrollment of the first patient for multiple registration trials, and regulatory milestone payments based on regulatory approval progress and commercial milestone payments. In addition, the Company is also entitled to receive a double-digit percentage of royalties on net product sales of JSKN003.

JSKN003 is an anti-HER2 bispecific antibody-drug conjugate (bis-ADC), which is developed inhouse with Alphamab’s proprietary Glycan-specific conjugation platform. Compared with its ADC counterparts, JSKN003 demonstrated better serum stability and stronger bystander effect, which effectively expands the therapeutic window. Multiple clinical data presented at several international academic conferences demonstrated favorable tolerability and safety profile, with promising efficacy of JSKN003 in heavily pretreated patients with advanced solid tumors.

About JSKN003

JSKN003 is an anti-HER2 bispecific antibody-drug conjugate (bis-ADC), which is developed inhouse with Alphamab’s proprietary Glycan-specific conjugation platform. Compared with its ADC counterparts, JSKN003 demonstrated better serum stability and stronger bystander effect, which effectively expands the therapeutic window. Multiple clinical studies of JSKN003 are currently being conducted in Australia and China, and we are also actively making the progress in its pivotal clinical trial in advanced HER2 low-expression breast cancer in China.

On September, 30 2024 VAR2 Pharmaceuticals ApS (‘VAR2 Pharma’) reported the company has received regulatory approval for their first-in-human Phase 0 clinical trial (Press release, Var2 Pharmaceuticals, SEP 30, 2024, View Source [SID1234646933]). In this study, the safety, tolerability, and biodistribution of two zirconium-89 labeled single-chain variable Fragments (scFvs) will be evaluated using PET/CT molecular imaging. The Danish company VAR2 Pharma is collaborating with TRACER, a CRO specialized in molecular imaging trials. The study will be conducted in the Netherlands and patient recruitment will start next month.

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VAR2 Pharma’s antibodies ("Vartumabs") were shown to selectively bind tumors in preclinical studies and will now be tested for the first time in patients with various types of solid cancers. By including multiple cancer indications, this study aims to evaluate the safety, tolerability, and biodistribution of two Vartumabs.

The study, designed by TRACER CRO, will include 16 patients per compound. Each participant will be administered a microdose which has no therapeutic intent but is sufficient for PET imaging. An important secondary objective of this study is to identify which tumor indications show the best uptake to inform subsequent clinical studies. Showing tumor-specific binding in humans is expected to pave the way for the development of oncology therapeutics and diagnostics based on Vartumabs.

About oncofetal chondroitin sulfate

Oncofetal chondroitin sulfate is an unusually long sugar chain with a heavy sulfation pattern presenting as a secondary modification in several cancer-associated proteoglycans. VAR2 Pharmaceuticals has since 2015 shown in several peer-reviewed publications that oncofetal chondroitin sulfate is expressed in 95% of cancers with little to no expression detected in healthy tissues beyond the placenta. Read more about oncofetal chondroitin sulfate in our seminal publication: Salanti et al. 2015.

About Vartumabs

Vartumabs are a novel class of antibodies that bind specifically to oncofetal chondroitin sulfate. VAR2 Pharmaceuticals has shown that Vartumabs are efficacious and safe as cancer therapies in a range of preclinical models and as different therapeutic modalities, including antibody-drug conjugates, bispecifics, and T-cell therapies. Read more about Vartumabs in our seminal publication: Vidal-Calvo et al. 2024.

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 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 29, 2024 IASO Biotherapeutics ("IASO Bio"), a biopharmaceutical company dedicated to discovering, developing, manufacturing and commercializing innovative cell therapy and antibody products, reported a poster presentation of the comparative clinical outcomes of patients from FUMANBA-1 study with relapsed/refractory multiple myeloma (R/R MM) who received the fully human anti-BCMA CAR-T cell therapy Equecabtagene Autoleucel (Eque-cel, Fucaso) under different lymphodepletion regimensat the 2024 International Myeloma Society (IMS) Annual Meeting (Press release, IASO Biotherapeutics, SEP 29, 2024, IASO Bio Presented Comparative Clinical Outcomes on the Optimal Lymphodepletion Prior to Infution of Equecabtagene Autoleucel（FucasoTM）in Patients with Relapsed Refractory Multiple Myeloma at 2024 IMS Annual Meeting [SID1234646909]). Results indicate that a full lymphodepletion dose can significantly improve the depth and duration of remission, prolong progression-free survival, without more treatment-related toxicity in patients.

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Abstract Number：P-094
Abstract Title: The Optimal Lymphodepletion Prior to Eque-cel in Patients with Refractory Relapsed Multiple Myeloma in FUMANBA-1 Study
Presentation Date：September 28, 2024（UTC-3)

The poster presents a post-hoc analysis of the FUMANBA-1 study which enrolled 91 subjects without prior CAR-T treatment to receive Eque-cel. The median follow-up period was 18.07 months. Of the 91 subjects, 33 underwent a lymphodepletion dose adjustment, while the remaining 58 received the standard lymphodepletion dose. Both groups had similar baseline characteristics, including age range, physical fitness scores, tumor staging, high-risk cytogenetic abnormalities, and previous lines of treatment.

The results indicate that, in terms of efficacy, the overall response rate (ORR) and stringent complete remission rate (sCR) for the standard-dose group were 100% and 82.8%, respectively, while the dose-adjusted group had rates of 97% and 78.8% .The standard-dose group also exhibited greater remission depth and better long-term prognosis, with 92.2% of patients maintaining a duration of response (DOR) exceeding one year, compared to 70.6% in the dose-adjusted group. Additionally, the median time to achieve minimal residual disease (MRD) negativity was longer in the dose-adjusted group at 22 days, compared to 15 days in the standard-dose group. The 12-month MRD negativity rate was 90.4% in the standard-dose group, significantly higher than the 63.7% observed in the dose-adjusted group (HR=3.33, P=0.0166). Regarding the 12-month progression-free survival (PFS) rate, the standard-dose group achieved 92.2% with a median PFS not yet reached, while the dose-adjusted group had a 12-month PFS of 73.5% and a median PFS of 30.28 months (HR=3.64, P=0.0032). A similar trend was noted in PFS among patients receiving a 90% dose adjustment.

In terms of safety, no significant differences in the severity and incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. CRS (grades 1-2) occurred in 94.8% of the standard dose group and 93.9% of the dose-adjusted group, with no severe CRS (≥grade 3) in either group. Apart from one grade 2 ICANS case in the adjusted group, no ICANS (≥grade 3) occurred in either group .

Conclusions：lymphodepletion prior to CAR-T cell therapy is essential for achieving optimal CAR-T efficacy. The study further confirms that appropriate lymphodepletion regimen is crucial for effectiveness of eue-cel treatment, significantly improving treatment outcomes and prognosis. When patients can tolerate it, administering the full lymphodepletion doses, when possible, can lead to greater benefits without increasing toxicity.

The principal investigator of this study, Professor Lugui Qiu, from the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and Professor Chunrui Li, from Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, stated: "The lymphodepletion regimen is crucial for CAR-T cell therapy. Data from this study indicate that standardized and sufficient lymphodepletion can lead to a higher quality of remission and more ideal clearance of minimal residual disease without increasing the potential of adverse reactions. These findings provide a scientific basis to ensure the efficacy and safety of CAR-T cell therapy through optimizing regimens of lymphodepletion, which will ultimately lead to longer survival and improved quality of life for patients with R/R MM."

Dr. Yongke Zhang, Chief Scientific Officer of IASO Bio, said: "We are delighted to present new finding from our FUMANBA-1 study. This study demonstrated the critical role of standard lymphodepletion in enhancing treatment outcomes and prognosis for patients.. these findings will contribute significantly to the establishment and optimization of lymphodepletion preconditioning standards in the field of CAR-T cell therapy, Our goal is to drive the standardization of industry practices, ensuring that every patient receiving CAR-T therapy benefits from a more scientific and efficient treatment plan."

About FUMANBA-1 Study

The FUMANBA-1 Study is a Phase Ib/II, single-arm, multicenter study to assess the efficacy and safety of the investigational drug Equecabtagene Autoleucel, a fully human BCMA CAR-T cell therapy, in patients with R/R MM who have received 3 or more lines of treatment.