On March 5, 2025 Akeso, Inc. (9926. HK) ("Akeso" or the "Company") reported the completion of patient enrollment for its Phase III registrational clinical trial (COMPASSION-22/AK104-306) evaluating cadonilimab, the world’s first PD-1/CTLA-4 bispecific antibody independently developed by the company, as an adjuvant treatment for hepatocellular carcinoma (HCC) with high recurrence risk following curative resection or ablation (Press release, Akeso Biopharma, MAR 5, 2025, View Source [SID1234650916]).

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The completion of patient enrollment in the COMPASSION-22/AK104-306 trial marks a significant milestone in the clinical development of cadonilimab for HCC. In addition to this Phase III study, another Phase III trial investigating cadonilimab in combination with lenvatinib and transarterial chemoembolization (TACE) for the treatment of unresectable intermediate to advanced HCC is currently progressing on schedule. The extensive exploration of combination therapies involving cadonilimab for HCC is expected to offer more effective treatment options for both early-stage and advanced HCC patients.

HCC is one of the most common malignant tumors globally. According to 2024 data, there are about 865,000 new cases of liver cancer worldwide, with 370,000 occurring in China. The recurrence rate after surgery is high, especially in patients with high-risk factors, with a five-year recurrence rate exceeding 70%. Currently, no standard adjuvant treatment exists for HCC in clinical practice. Identifying effective adjuvant therapies to reduce recurrence risk and extend survival is a critical unmet need in HCC treatment.

Cadonilimab is the world’s first approved bispecific immunotherapy for cancer. Previous studies have shown its significant efficacy and favorable safety profile in treating HCC. Research presented at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia Annual Meeting demonstrated that cadonilimab combined with FOLFOX-HAIC as neoadjuvant therapy for resectable multinodular HCC achieved a 100% disease control rate (DCR) with manageable safety. Furthermore, data from the 2023 ESMO (Free ESMO Whitepaper) Congress highlighted that cadonilimab combined with lenvatinib as a first-line treatment for advanced HCC showed superior antitumor activity compared to approved therapies, effectively controlling tumor progression and offering long-term survival benefits over current treatment options.

Akeso will continue to advance cadonilimab clinical development for multiple malignant tumors, with the aim to provide more therapeutic options for patients worldwide. Currently, cadonilimab is currently involved in over 23 clinical studies across 16 indications, including gastric cancer, lung cancer, liver cancer, cervical cancer, and pancreatic cancer. It has already received approval for the treatment of recurrent/metastatic cervical cancer and first-line gastric cancer. The sNDA for cadonilimab for the treatment of first-line cervical cancer is currently under review. Additionally, five Phase III trials for HCC, non-small cell lung cancer (NSCLC), and gastric cancer are underway. Studies across multiple indications, including cervical cancer, gastric cancer, and NSCLC, have shown that cadonilimab offers meaningful efficacy benefits in all patient populations, regardless of PD-L1 expression levels (high, low, or negative). These patient data indicates that cadonilimab can also significantly broadens the eligible patient population that can benefit from cancer immunotherapies.

On March 5, 2025 Galectin Therapeutics presented its corporate presentation (Presentation, Galectin Therapeutics, MAR 5, 2025, View Source [SID1234650901]).

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On March 5, 2025 CStone Pharmaceuticals ("CStone", HKEX: 2616), a biopharmaceutical company dedicated to developing innovative cancer therapies, reported the submission of a Phase Ib clinical trial application in Australia for CS5001, its ROR1-targeting antibody-drug conjugate (ADC), in combination with first-line standard-of-care (SoC) for DLBCL (Press release, CStone Pharmaceauticals, MAR 5, 2025, View Source [SID1234650917]). CS5001 is also being evaluated as both a monotherapy and in combination with a PD-L1 inhibitor for advanced solid tumors in an ongoing global multi-center clinical trial.

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Building on promising data from CS5001 monotherapy in later-line aggressive and indolent lymphomas, this Phase Ib trial aims to expand the therapeutic potential of CS5001 across all DLBCL stages and solid tumors. The study will explore:

CS5001 + R-CHOP: First-line treatment for DLBCL patients who have not received prior systemic therapy.
CS5001 + SoC: For patients with relapsed or refractory DLBCL.
CS5001 Monotherapy: Targeting ROR1-expressing solid tumors.
CS5001 + Sugemalimab: Combination therapy for advanced solid tumors.
Dr. Jason Yang, CEO, President of R&D, and Executive Director at CStone, stated: "We are thrilled to reach another key clinical milestone for CS5001. The existing data underscore its broad potential in both lymphomas and solid tumors. Notably, a ROR1 ADC combined with R-CHP has demonstrated an impressive complete response (CR) rate in a Phase II trial for first-line DLBCL. As we advance from late-line monotherapy to frontline combination therapy, we are optimistic that CS5001 will provide significant clinical benefits to DLBCL patients and establish itself as a first-line treatment option. Meanwhile, we continue to explore CS5001’s potential in solid tumors and eagerly anticipate further positive outcomes."

The global multi-center Phase Ib trial for CS5001 is actively enrolling patients across the United States, Australia, and China. Recruitment is ongoing for monotherapy cohorts targeting aggressive and indolent advanced lymphomas, which could potentially expand into a Phase II single-arm registrational study. Additional cohorts, including the first-line DLBCL combination therapy and solid tumor monotherapy and combination therapy arms, will be initiated soon.

About CS5001 (ROR1 ADC)

CS5001 is a clinical-stage antibody-drug conjugate ("ADC") targeting ROR1 (receptor tyrosine kinase-like orphan receptor 1). CS5001 has been uniquely designed with proprietary tumor-cleavable linker and pyrrolobenzodiazepine ("PBD") prodrug. Only after reaching the tumor, the linker and prodrug are cleaved to release the PBD toxin, resulting in lethal DNA cross-links in cancer cells. The use of the linker plus PBD prodrug effectively helps address the toxicity associated with traditional PBD payloads, leading to a better safety profile. CS5001 has demonstrated complete tumor suppression in several preclinical cancer models and demonstrated favorable serum half-life and pharmacokinetic characteristics. CS5001 is a promising candidate drug with precision treatment potential in both hematologic tumors and malignant solid tumors. Additionally, CS5001 utilizes site-specific conjugation for a precise drug antibody ratio of which enables homogeneous production and large-scale manufacturing.

In October 2020, CStone signed a licensing agreement with LigaChem Biosciences, Inc. (LCB) for the development and commercialization of CS5001 which was originally generated by collaboration of LCB and ABL Bio, both South Korea-based leading biotech companies. Under the agreement, CStone obtains the exclusive global right to develop and commercialize CS5001 outside the Republic of Korea.

The first-in-human data for CS5001 in patients with advanced solid tumors and lymphomas was presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Additionally, the latest clinical data on CS5001 as a monotherapy in patients with advanced lymphomas has recently been presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

CS5001 has demonstrated encouraging safety and robust anti-tumor activity in the Phase 1a dose escalation trials across 10 dose levels.

At the tentative recommended Phase 2 dose (RP2D) of DL8 (125 μg/kg), CS5001 achieved objective response rates (ORRs) of 70% in advanced B-cell lymphoma and 100% in Hodgkin lymphoma.
Encouraging efficacy signals were also observed in advanced solid tumors, including non-small cell lung cancer and pancreatic cancer.
CS5001 was well tolerated in heavily pre-treated patients with advanced B-cell lymphomas and solid tumors.

On March 5, 2025 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) ("Jazz" or the "Company") and Chimerix (Nasdaq: CMRX) ("Chimerix"), reported the companies have entered into a definitive agreement for Jazz to acquire Chimerix for $8.55 per share in cash, representing a total consideration of approximately $935 million (Press release, Jazz Pharmaceuticals, MAR 5, 2025, View Source [SID1234650902]). The transaction has been approved by both companies and is expected to close in the second quarter of 2025.

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Chimerix’s lead clinical asset is dordaviprone, a novel first-in-class small molecule treatment in development for H3 K27M-mutant diffuse glioma, a rare, high-grade brain tumor that most commonly affects children and young adults. There are no U.S. Food and Drug Administration (FDA)-approved therapies specifically for H3 K27M-mutant diffuse glioma patients; radiation is the most common treatment approach. A New Drug Application (NDA) for accelerated approval of dordaviprone in recurrent H3 K27M-mutant diffuse glioma was recently accepted and granted Priority Review by FDA. FDA has set a target Prescription Drug User Fee Act (PDUFA) action date of August 18, 2025. If approved in the U.S., dordaviprone may be eligible for a Rare Pediatric Disease Priority Review Voucher (PRV). Separately, dordaviprone is being studied in the ongoing Phase 3 ACTION trial, evaluating its use in newly diagnosed, non-recurrent H3 K27M-mutant diffuse glioma patients following radiation treatment, potentially extending this treatment option into the front-line setting.

"Adding dordaviprone to our oncology R&D pipeline will further diversify our portfolio with a medicine that addresses a significant unmet need with no other FDA-approved therapies and limited treatment options for this patient population. If approved, dordaviprone has the potential to rapidly become a standard of care for a rare oncology disease and also contribute durable revenue beginning in the near-term," said Bruce Cozadd, chairman and chief executive officer, Jazz Pharmaceuticals. "We are encouraged by the dordaviprone clinical trial results to date and look forward to closing the proposed acquisition and working with our new colleagues from Chimerix to fully leverage our combined R&D and commercial expertise to deliver this novel therapy to patients, beginning as early as the second half of this year."

"We are excited to reach this agreement with Jazz Pharmaceuticals as they bring global scale to broaden our dordaviprone commercial strategy," said Mike Andriole, President and CEO of Chimerix. "The transaction, if approved, provides the opportunity to advance access to dordaviprone to reach more patients globally. This announcement is the culmination of years of scientific work by our incredibly talented team, and will deliver significant and certain value to our shareholders."

Key Highlights

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Strategic fit that will strengthen Jazz’s presence in the rare oncology space and reinforces commitment to patients with rare diseases with significant unmet need

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Dordaviprone has been shown to benefit patients with recurrent H3 K27M-mutant diffuse glioma across several clinical studies, with a consistently favorable safety profile both as monotherapy and in combination with other treatment approaches including radiation

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With no currently approved therapies for H3 K27M-mutant diffuse glioma patients, dordaviprone has the potential to rapidly become a standard of care and a meaningful therapy for patients with limited treatment options

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Potential near-term commercial launch in the U.S., if approved

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FDA has accepted an NDA for dordaviprone seeking accelerated approval for treatment of H3 K27M-mutant diffuse glioma in adult and pediatric patients with progressive disease following prior therapy

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NDA has been granted Priority Review and assigned a PDUFA target action date of August 18, 2025

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Following the closing of the proposed acquisition and in collaboration with its new colleagues from Chimerix, Jazz plans to leverage its combined development and commercial capabilities to continue advancing the dordaviprone clinical trial program and execute a strong commercial launch, if approved in the U.S.

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Will create an additional durable revenue opportunity for Jazz with patent protection into 2037, with potential to receive patent term extension

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Ongoing Phase 3 ACTION trial has potential to confirm clinical benefit of dordaviprone in recurrent H3 K27M-mutant diffuse glioma and extend its use to front-line patients

Transaction Terms

Under the terms of the merger agreement, Jazz will commence an all-cash tender offer to acquire all outstanding shares of Chimerix’s common stock, whereby Chimerix shareholders will be offered $8.55 per share in cash, representing a total consideration of approximately $935 million. This reflects an approximately 72% premium based on the closing trading price on March 4, 2025. Upon the successful completion of the tender offer, Jazz will acquire all shares not acquired in the tender through a second-step merger for the same consideration per share paid in the tender offer.

Jazz expects to fund the transaction through existing cash and investments.

Closing Conditions

The transaction is subject to customary closing conditions, including the tender of a majority of the outstanding shares of Chimerix’s voting common stock and other conditions. Chimerix’s Board of Directors unanimously recommends that Chimerix shareholders tender their shares in the tender offer.

Advisors

Guggenheim Securities is serving as financial advisor to Jazz Pharmaceuticals, and Wachtell, Lipton, Rosen & Katz is serving as legal advisor.

Centerview Partners LLC is serving as financial advisor to Chimerix, and Skadden, Arps, Slate, Meagher & Flom LLP and Cooley LLP are serving as legal advisors.

About Dordaviprone

Dordaviprone (ONC201) is a novel first-in-class small molecule imipridone that selectively targets the mitochondrial protease ClpP and dopamine receptor D2 (DRD2). Dordaviprone’s unique mechanism of action includes alterations of key epigenetic modifications such as reversal of H3 K27me3-loss, which is the hallmark of H3 K27M-mutant gliomas.

On March 5, 2025 Laminar Pharma, a leader in the development of innovative cancer therapy based on membrane lipid therapy, reported optimistic results from its ongoing clinical trial evaluating LAM561 for the treatment of newly diagnosed glioblastoma (ndGBM), the most aggressive form of brain cancer, that has seen limited clinical improvement in the last 20 years (Press release, Laminar Pharma, MAR 5, 2025, View Source [SID1234650918]). The trial, partially funded with an EU H2020 Grant (ClinGlio), has shown an improvement trend in progression-free survival (PFS) in MGMT-methylated patients receiving LAM561 in combination with chemoradiotherapy (radiotherapy plus temozolomide) as the standard of care (SoC) compared to placebo plus SoC treatment. LAM561 is available for in-license for all territories. Laminar’s current fund raising round is still open, for a limited time, to additional investors.

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The pivotal phase 2b/3 trial, "A randomized, double-blind, placebo-controlled adjuvant trial in newly diagnosed primary glioblastoma subjects to assess the efficacy and safety of LAM561 in combination with radiotherapy and temozolomide standard of care treatment" (NCT04250922), enrolled 144 patients with newly diagnosed glioblastoma. In November 2024, After reaching 66 PFS events the independent data monitoring committee (IDMC) recommended: (1) Continue the trial without modifications until 90 OS events (overall survival), when the final analysis will be carried out, estimated for Q4 2026; (2) that the trial should not be stopped for reasons of safety or futility and (3) opening the study, that is, removing the blind. From that moment, patients, doctors and Laminar as sponsor are able to know if any patient received placebo or LAM561.

Although the main primary outcome of the interim analysis (Hazard Ratio of 0.5 for PFS) was not reached for the whole trial population, the unblinding of the trial has allowed Laminar to conduct an ongoing evaluation (non-statistically assessed and with data under monitoring review) considering the per protocol predefined stratification: methylation status of the MGMT promoter and RTOG score (3, 4 or 5), a scale describing the side effects caused by radiation therapy and the higher the RTOG score the worse the clinical position. By revising the data stratified by MGMT promoter methylation status and RTOG, and using data available on 18th February 2025, the median PFS for methylated patients RTOG3 was 56,7 weeks on the LAM561 treatment arm against 19 weeks on the placebo arm (n=9). Moreover, the median PFS for methylated patients RTOG4 was 86,4 weeks on the LAM561 treatment arm against 54,7 weeks on the placebo arm (n=39). With currently available data, methylated patients treated with LAM561 + SoC seem to experience a potentially clinically relevantimprovement in PFS (Hazard-ratio estimation of 0.53) compared to control group (placebo+SoC). PFS was not improved by LAM561 in unmethylated patients. This interim perspective should be taken with caution since the study is still ongoing and providing new information and the final interpretation will only be apparent once the study has completed after reaching 90 OS events; and, although progression of the disease is a relevant clinical event, overall survival is the primary outcome of the trial and conclusions on the final effect of the drug need to wait until the final analysis is performed and data is reviewed by the IDMC. Laminar intends to perform an in-depth independent objective assessment of the findings.

The methylation status of the MGMT promoter is highly relevant in the prognosis of glioblastoma [Leske et al., 2023]. MGMT-methylated patients represent 35-50% of the total glioblastoma patients.

"We are encouraged by the progression-free survival results from this trial in MGMT-methylated patients, which, if reflected by positive overall survival results, may represent a significant advance in the treatment of glioblastoma, a condition with poor prognosis that affects more than 100,000 people every year", said Dr. Pablo Escribà, CEO of Laminar Pharma. "Glioblastoma remains one of the most challenging cancers to treat, and these findings highlight the potential of LAM561 to improve outcomes for methylated patients, a considerable portion of the total glioblastoma population. Our team is committed to continuing the development of this promising therapy."

The combination of LAM561 and SoC was well-tolerated. The safety data in the trial is consistent with the known safety profile of LAM561 studied in previous clinical trials, with no new safety signals observed in the combination arm.

Trial Details and Key Findings:

The study enrolled 144 patients with newly diagnosed, IDH-wildtype, glioblastoma.

MGMT-methylated patients treated with LAM561 and SoC currently show a trend towards longer progression-free survival (86,4 weeks) compared to placebo control SoC group (54,7 weeks, HR 0.53). The study will continue until 90 OS events when final analysis will be conducted, estimated by late 2026.

Safety data showed that the treatment was well-tolerated, with adverse events consistent with previous trials and a well-known safety profile.
These results built on earlier preclinical and clinical data, which indicated that LAM561 could effectively target, through modification of the membrane lipid, the molecular pathways associated with glioblastoma growth. Further analysis and longer follow-up periods are underway to assess overall survival and other secondary endpoints.

About Glioblastoma: Glioblastoma (GBM) is the most common primary malignant brain tumor and accounts for nearly 50 percent of all gliomas and approximately 25 percent of all primary brain and CNS malignant tumors. The incidence of GBM in Europe is currently above 25,000 new cases each year, rising to over 100,000 cases per year worldwide. The prognosis for GBM patients is very poor, with a median survival time of about 14.5 months despite optimum chemo-radiation treatment. About 15% of patients survive two years after diagnosis and ca. 4% survive for five or more years. In this scenario, there is a desperate need for novel treatment alternatives that provide safe and more efficacious clinical outcomes.

About LAM561: LAM561 (2-hydroxyoleic acid (2-OHOA); idroxioleic acid, sodium) is a synthetic derivative of oleic acid and the most advanced Laminar’s R&D product which is taken orally. This drug alters the composition of the plasma membrane in cancer cells, reducing the activity of membrane-associated signaling proteins that are known to promote tumor growth and affecting tumors in the brain. LAM561 is in the process of completing its last clinical development phase and has shown promising preliminary clinical activity in the treatment of aggressive brain tumors, glioblastoma.