On March 31, 2025 AstraZeneca reported that Calquence (acalabrutinib) in combination with bendamustine and rituximab has been recommended for approval in the European Union (EU) for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are not eligible for autologous hematopoietic stem cell transplantation (Press release, AstraZeneca, MAR 31, 2025, View Source [SID1234651659]).

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on the results from the ECHO Phase III trial which were presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Congress.

Results from the ECHO trial showed Calquence plus bendamustine and rituximab reduced the risk of disease progression or death by 27% compared to standard-of-care chemoimmunotherapy (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.57-0.94; p=0.016). Median progression-free survival (PFS) was 66.4 months for patients treated with the Calquence combination versus 49.6 with chemoimmunotherapy alone.

This recommendation for Calquence as a combination treatment in the 1st-line MCL setting follows the recent CHMP positive opinion for Calquence as a monotherapy for the treatment of adult patients with relapsed or refractory MCL.

Martin Dreyling, MD, Department of Medicine, University Hospital LMU Munich, and investigator in the trial, said: "Results from the pivotal ECHO trial demonstrated the significant benefits of the Calquence combination in managing this rare and aggressive cancer. Today’s recommendation is an important advance within the mantle cell lymphoma first-line treatment landscape, especially for older patients who need a balance of efficacy and tolerability."

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "Today’s positive recommendation from the CHMP further reinforces the potential of Calquence to advance first-line treatment options in mantle cell lymphoma, with the Calquence combination demonstrating an almost one and a half year improvement in progression-free survival in this setting. If approved, Calquence has the potential to transform the standard of care as the first BTK inhibitor approved for these patients in Europe."

MCL is a rare and typically aggressive form of non-Hodgkin lymphoma, often diagnosed at an advanced stage.1,2 It is estimated that more than 6,000 patients were diagnosed with MCL in the UK, France, Germany, Spain and Italy in 2024.3

The safety and tolerability of Calquence was consistent with its known safety profile, and no new safety signals were identified.

Calquence plus bendamustine and rituximab is approved in the US and several other countries in this setting based on the ECHO results. Regulatory applications are currently under review in Japan and several other countries in this indication.

Notes

Mantle cell lymphoma (MCL)
While MCL patients initially respond to treatment, patients do tend to relapse.4 MCL comprises about 3-6% of non-Hodgkin lymphomas, with an annual incidence of 0.5 per 100,000 population in Western countries; It is estimated that there are more than 21,000 patients diagnosed with MCL in the US, UK, France, Germany, Spain, Italy, Japan and China.5

ECHO
ECHO is a randomised, double-blind, placebo-controlled, multi-centre Phase III trial evaluating the efficacy and safety of Calquence plus bendamustine and rituximab compared to SoC chemoimmunotherapy (bendamustine and rituximab) in adult patients at or over 65 years of age (n=635) with previously untreated MCL.6 Patients were randomised 1:1 to receive either Calquence or placebo administered orally twice per day, continuously, until disease progression or unacceptable toxicity. Additionally, all patients received six 28-day cycles of bendamustine on days 1 and 2 and rituximab on day 1 of each cycle, followed by rituximab maintenance for two years if patients achieved a response after induction therapy.6

The primary endpoint is PFS assessed by an Independent Review Committee; other efficacy endpoints include overall survival (OS), overall response rate (ORR), duration of response (DoR) and time to response (TTR).6 The trial was conducted in 27 countries across North and South America, Europe, Asia and Oceania.6

The ECHO trial enrolled patients from May 2017 to March 2023, continuing through the COVID-19 pandemic. Prespecified PFS and OS analyses censoring for COVID-19 deaths were conducted to assess the impact of COVID-19 on the study outcome in alignment with the FDA. Patients with blood cancer remain at a disproportionately high risk of severe outcomes from COVID-19, including hospitalisation and death compared to the general population.6,7,8

Calquence
Calquence (acalabrutinib) is a second-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.8 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.

Calquence is approved for the treatment of chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) in the US and Japan, approved for CLL in the EU and many other countries worldwide and approved in China for relapsed or refractory CLL and SLL. Calquence is also approved for the treatment of adult patients with previously untreated MCL in the US and other countries. It is also approved for the treatment of adult patients with MCL who have received at least one prior therapy in the US, China and several other countries. Calquence is not currently approved for the treatment of MCL in Japan.

As part of an extensive clinical development programme, Calquence is currently being evaluated as a single treatment and in combination with standard-of-care chemoimmunotherapy for patients with multiple B-cell blood cancers, including CLL, MCL and diffuse large B-cell lymphoma.

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On March 31, 2025 Aprea Therapeutics, Inc. (Nasdaq: APRE) ("Aprea", or the "Company"), a clinical-stage biopharmaceutical company developing innovative treatments that exploit specific cancer cell vulnerabilities while minimizing damage to healthy cells, reported that a patient with HPV+ head and neck squamous cell carcinoma (HNSCC) has been dosed in the ongoing ACESOT-1051 clinical trial evaluating APR-1051 (Press release, Aprea, MAR 31, 2025, View Source [SID1234651658]). This is the first patient to be dosed in Cohort 5 (70 mg once daily) of the study. Open label data from the study are expected in the second half of 2025.

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WEE1 inhibition has emerged as a promising strategy for targeting tumor cells with high replication stress and DNA damage accumulation. HPV driven cancers, including HPV+ HNSCC, are characterized by defects in the DDR pathway, making them potentially susceptible to WEE1 inhibition. HPV+ cancers are those where the underlying cause is persistent infection with human papillomavirus, a group of viruses that infect the skin and mucous membranes. A high proportion of HNSCC cases are attributable to HPV. An estimated 70% of the 20,000 cases of oropharyngeal squamous cell carcinoma (HNSCC that occurs in the oropharynx) seen annually in the US are attributable to HPV.

APR-1051 is a potent and selective small molecule that has been designed to potentially solve tolerability challenges of the WEE1 class. The ongoing ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) clinical trial is a Phase 1 trial evaluating single-agent APR-1051 in patients with advanced solid tumors harboring cancer-associated specific gene alterations.

"Enrollment of the first patient with HPV+ head and neck cancer in the Phase 1 ACESOT-1051 trial is an important step and is in line with our goal of identifying patient populations most likely to benefit from WEE1 inhibition," said Philippe Pultar MD., Senior Medical Advisor and Lead WEE1 Clinical Development of Aprea. "We are pleased with the progress of the trial and encouraged by the safety profile of APR-1051 to date. We look forward to continuing the study as we work toward identifying the optimal dose for future studies. We continue to believe that APR-1051 has best in class potential."

The latest patient in ACESOT-1051 was enrolled at MD Anderson Cancer Center. Aprea recently entered into a Material Transfer Agreement (MTA) with MD Anderson to support preclinical research aimed at exploring the potential of APR-1051 in treating HPV+ and HPV- head and neck squamous cell carcinoma (HNSCC) expressing genomic markers of replication stress.

ACESOT-1051 Study Design

ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) is designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent APR-1051 in advanced solid tumors harboring cancer-associated gene alterations. Oral APR-1051 will be administered once daily for 28-day cycles. The study consists of two parts. Part 1 is dose escalation and is expected to enroll up to 39 patients with advanced solid tumors. The first three dose levels (10mg, 20mg and 30mg) used accelerated titration. Bayesian Optimal Interval (BOIN) design is now being employed for the remaining dose levels (50mg and above). Part 2 (up to 40 patients) is designed for dose optimization, with the goal of selecting the Recommended Phase 2 Dose (RP2D).

The primary objectives of the study are to measure safety, dose-limiting toxicities (DLTs), maximum tolerated dose or maximum administered dose (MTD/MAD), and RP2D; secondary objectives are to evaluate pharmacokinetics, preliminary efficacy according to RECIST or PCWG3 criteria; pharmacodynamics is an exploratory objective. The University of Texas MD Anderson Cancer Center is the lead site, and the study will be performed at between 3 and 10 sites in the U.S. For more information refer to clinicaltrials.gov NCT06260514.

On March 31, 2025 Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage biopharmaceutical company focused on developing innovative treatments for patients with unmet medical needs, reported fourth quarter and full-year 2024 financial results and summarized recent developments (Press release, Monopar Therapeutics, MAR 31, 2025, View Source [SID1234651636]).

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"2024 was a productive year for Monopar, with the in-licensing of ALXN1840, the initiation of two first-in-human radiopharma Phase 1 clinical trials, and the strengthening of our balance sheet with net proceeds of over $55 million from financings," said Chandler Robinson, MD, Chief Executive Officer of Monopar. "We are especially grateful to the Wilson disease patients. Their testimonies and support are what provided the opportunity for Monopar to progress ALXN1840 toward an NDA filing."

Recent Program Developments

ALXN1840 – Plan to Submit NDA with FDA for Wilson Disease in Early 2026

Wilson disease is a rare and progressive genetic condition in which the body’s pathway for removing excess copper is compromised, leading to damage from toxic copper build-up in tissues and organs such as the liver and brain. ALXN1840 is a potent binder and mobilizer of copper, as demonstrated in a Phase 3 clinical trial that met its primary endpoint. In October 2024, Monopar announced the execution of a worldwide exclusive license to ALXN1840 with Alexion, AstraZeneca Rare Disease ("AZ"). As part of this transaction, AZ received a total cash payment of $4.0 million, was issued 9.9% ownership of Monopar’s outstanding common stock, and is entitled to receive regulatory approval and sales milestones along with a tiered royalty based on net sales

MNPR-101 – Currently Enrolling Phase 1 Imaging and Therapeutic Oncology Trials

Imaging agent MNPR-101-Zr (MNPR-101 conjugated to zirconium-89) and therapeutic agent MNPR-101-Lu (MNPR-101 conjugated to lutetium-177) target the urokinase plasminogen activator receptor ("uPAR"), which is expressed in numerous aggressive cancers such as triple-negative breast, colorectal, and pancreatic cancers

●

Initiated Phase 1a clinical trial for novel therapeutic radiopharmaceutical MNPR-101-Lu in patients with advanced cancers

●

Dosed first patient with MNPR-101-Lu in December 2024

●

Presented encouraging human clinical imaging and dosimetry data of MNPR-101-Zr at the European Association of Nuclear Medicine ("EANM") 2024 Annual Congress

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uPAR expression, as detected by MNPR-101-Zr, has been seen to date in breast, colorectal, pancreatic, adrenocortical carcinoma, and ovarian cancer patients

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Filed a patent application covering new therapeutic radiopharmaceuticals based on a novel family of linkers used to connect radioisotopes with targeting agents, including Monopar’s uPAR targeting antibody MNPR-101

Recent Financings

In Q4 2024, we raised net proceeds of over $55 million from the following financings:

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On October 30, 2024, pursuant to a placement agent agreement with Rodman & Renshaw LLC, we sold 1,181,540 shares of our common stock at $16.25 in a public offering, yielding net proceeds of approximately $17.8 million.

●

On December 23, 2024, pursuant to an underwriting agreement with Piper Sandler & Co., we sold 798,655 shares of our common stock at $23.79 per share in a public offering. Concurrently with the public offering, we completed a private placement of 882,761 pre-funded warrants to purchase shares of common stock to an institutional investor at a purchase price of $23.789 per pre-funded warrant. The net proceeds of the December 23, 2024, public offering and private placement were approximately $37.4 million.

Results for the Fourth Quarter and Year Ended December 31, 2024, Compared to the Fourth Quarter and Year Ended December 31, 2023

Cash and Net Loss

Cash, cash equivalents and short-term investments as of December 31, 2024, were $60.2 million. Monopar expects that its current funds will be sufficient to continue operations at least through December 31, 2026, in order to: (1) assemble a regulatory package and file an NDA for ALXN1840; (2) continue to conduct and conclude its first-in-human imaging and dosimetry clinical trial with MNPR-101-Zr; (3) continue to conduct its first-in-human therapeutic clinical trial of MNPR-101-Lu; (4) advance its preclinical MNPR-101-Ac program into the clinic; and (5) invest in internal research and development projects to expand its radiopharma and rare disease pipeline.

Net loss for the fourth quarter of 2024 was $10.9 million or $2.23 per share compared to $1.8 million or $0.60 per share for the fourth quarter of 2023. Net loss for the year ended December 31, 2024, was $15.6 million or $4.11 per share compared to $8.4 million or $3.04 per share for the year ended December 31, 2023.

Research and Development ("R&D") Expenses

R&D expenses for the fourth quarter of 2024 were $9.9 million compared to $1.0 million for the fourth quarter of 2023. This increase of $8.9 million was primarily due to: (1) an increase of $8.6 million related to the in-licensing of ALXN1840 and (2) an increase of $0.4 million in R&D salaries, partially offset by a net decrease of $0.1 million in other R&D expenses.

R&D expenses for the year ended December 31, 2024, were $13.0 million compared to $5.6 million for the year ended December 31, 2023. This increase of $7.4 million was primarily due to: (1) an increase of $8.6 million related to the in-licensing of ALXN1840; (2) an increase of $0.3 million in R&D personnel expenses; and (3) a net increase of $0.1 million in other R&D expenses, partially offset by a decrease of $1.6 million in trial closure related expenses.

General and Administrative ("G&A") Expenses

G&A expenses for the fourth quarter of 2024 were $1.2 million, compared to $0.9 million for the fourth quarter of 2023. This increase of $0.3 million was primarily due to: (1) an increase of $0.1 million in G&A personnel salaries; (2) an increase of $0.1 million in G&A consulting fees; and (3) an increase of $0.1 million in Delaware franchise taxes.

G&A expenses for the year ended December 31, 2024, were $3.2 million, compared to $3.2 million for the year ended December 31, 2023.

On March 30, 2025 Akeso Inc. (9926.HK) ("Akeso", "the Company") reported its 2024 annual results, emphasizing the company’s key achievements in drug research, clinical development, and commercialization (Press release, Akeso Biopharma, MAR 30, 2025, View Source [SID1234651611]).

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In 2024, Akeso achieved key success in antibody therapy research and development. The approval of new indications for cadonilimab and the launch of first-in-class drugs like ivonescimab expanded the company’s footprint in major solid tumors, including lung and gastric cancers. Akeso continues to challenge current standard of care with head-to-head trials against pembrolizumab and other therapies, while advancing novel treatments such as anti-CD47 monoclonal antibody, antibody drug conjugates ("ADCs") and bispecific ADCs. The company also achieved major milestones in commercialization and patient access, with products included in national insurance directories. Currently, over 25 registrational and Phase III clinical trials are actively progressing.

On the commercial front, Akeso’s adjustments in drug pricing and optimization of its commercial systems led to new drug sales revenue surpassing RMB 2 billion in 2024, a 25% year-on-year increase. The company continues to reduce operating losses, with an EBITDA loss of 225 million RMB in 2024.

Dr. Xia Yu, Founder, Chairwoman, President, and CEO of Akeso Biopharma:

"We are thrilled to have reached historic milestones in our innovative drug development in 2024. The approval of several globally competitive products and breakthroughs in advanced therapies have strengthened our global competitiveness in biopharmaceutical innovation.

Notably, our first-in-class bispecific antibodies, cadonilimab and ivonescimab, have been approved for commercial sales and included in China’s NRDL. This significantly improves drug accessibility, reduces patient burdens, and fulfills a key strategic goal in our domestic commercialization efforts. In clinical development, cadonilimab and ivonescimab are currently in over 20 registrational/Phase III clinical trials globally, establishing a strong presence in first-line treatments for a wide range of high-incidence cancers. Additionally, more than 40 Phase II trials are ongoing, further strengthening our leadership in global cancer immunotherapy.

We’ve also made key advances in novel therapies, with ligufalimab (anti-CD47 mAb) moving to Phase III for solid tumors, and progress in next-gen ADCs, bispecific ADCs, and autoimmune bispecific antibodies.

These achievements have expanded our oncology pipeline and strengthened our global expansion strategy with a comprehensive ‘IO 2.0+’ combination therapy platform."

Akeso’s Bispecific Antibody Clinical Portfolio Continues to Expand, Demonstrating Global Leadership in Next-Generation Tumor Immunotherapy

In 2024, Akeso continued to focus and make progress on research and clinical development. The accomplishments from these efforts include :

3 novel drugs approved for market
5 NDAs under review for 5 indications
24 drug candidates in global clinical development
Over 25 registrational/Phase III trials actively progressing
Notably, Akeso has focused on redefining global treatment paradigms through the development of breakthrough therapies that provide additional survival and safety benefit to current standard of care. Centered around its internally developed first-in-class bispecific antibodies—cadonilimab (PD-1/CTLA-4) and ivonescimab (PD-1/VEGF)—the company has conducted over 40 clinical trials across a number of indications.

Cadonilimab

After its approval for recurrent/metastatic cervical cancer, cadonilimab reached a major milestone in 2024 with the approval for a new indication in first-line gastric cancer, addressing unmet needs in PD-L1 low/negative populations. The sNDA for first-line cervical cancer is currently under review. Cadonilimab is also currently in 8 Phase III trials and nearly 20 Phase II studies, exploring treatments for major cancers in both first- and later-line settings.

Ivonescimab

In 2024, ivonescimab was approved for the treatment of EGFR-TKI-resistant, locally advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC). A major milestone was reached in May 2024 when the Phase III HARMONi-2 trial, comparing ivonescimab to pembrolizumab in first-line PD-L1-positive NSCLC, showed positive results. Data presented at the 2024 World Conference on Lung Cancer (WCLC) revealed a median Progression-Free Survival (mPFS) of 11.14 months for ivonescimab, compared to 5.82 months for pembrolizumab. This breakthrough highlights ivonescimab’s potential as a key therapy in next-gen immuno-oncology and boosts its global commercialization prospects.

Currently, ivonescimab is in 12 registrational/Phase III clinical trials, including 6 head-to-head studies against PD-1/L1 therapies, as well as in over 20 Phase II trials.

Key Phase III Trials in NSCLC :

Ivonescimab monotherapy vs. pembrolizumab as first-line (1L) treatment for PD-L1+ NSCLC
Ivonescimab + chemotherapy vs. pembrolizumab + chemotherapy (global multicenter trial) as 1L treatment for NSCLC
Ivonescimab + chemotherapy vs. tislelizumab + chemotherapy as 1L treatment for squamous NSCLC (sq-NSCLC)
Phase III Trials in Other Major IO Indications:

Ivonescimab + chemotherapy vs. durvalumab + chemotherapy as 1L treatment for biliary tract cancer
Ivonescimab + AK117 (CD47 mAb) vs. pembrolizumab as 1L treatment for PD-L1+ head and neck squamous cell carcinoma (HNSCC)
Ivonescimab combination as 1L treatment for triple-negative breast cancer (TNBC)
Ivonescimab in PD-(L)1-resistant NSCLC, and ivonescimab combination as 1L treatment for pancreatic cancer (preparation/initiation underway)
These trials reflect ivonescimab’s development strategy that is based on a fundamental understanding of tumor immunobiology and designing clinical studies that compares it with standard of care, encompassing both first-line and later-line treatments for high-incidence, high-mortality cancers. This positions Akeso as a key innovator in next-generation cancer immunotherapy, improving and contributing to the global IO cancer treatment landscape.

Breakthrough Bispecifics Enter NRDL, Paving the Way for the Next Stage of Commercial Growth

In 2024, Akeso Biopharma achieved commercial sales of RMB 2 billion, representing a 25% year-over-year growth.

As China’s innovative drug market transforms, clinically innovative medicines face historic development opportunities. Both cadonilimab and ivonescimab, recognized for their innovation and clinical value, were successfully included in the National Reimbursement Drug List (NRDL) during the 2024 negotiations, marking a major milestone in Akeso’s commercial franchise.

The inclusion of both cadonilimab and ivonescimab in the NRDL represents the next stage in Akeso’s market strategy, with a clear focus on hospital-based markets as the core growth area. It greatly improves the therapy accessibility, reduces patient treatment burdens, and evolves the innovative value of the company’s first-in-class bispecific antibodies into tangible social and commercial benefits.

Following the NRDL inclusion, Akeso has made key upgrades to its commercial infrastructure, aligning with its strategic priorities for accelerated growth:

Rapid Hospital Access: Prioritizing swift hospital access for cadonilimab and ivonescimab through data-driven tiering of key accounts.
Commercial Team Expansion: Enhancing coverage of core hospitals and regional hubs to ensure maximum reach and impact.
Scientific Leadership: Strengthening engagement with KOLs and generating real-world evidence to highlight the differentiated efficacy and safety profiles of its bispecifics, driving physician adoption.
These initiatives set the stage for Akeso’s growth in 2025 and beyond, while building a strong foundation for long-term, sustainable commercial growth.

Akeso’s non-oncology portfolio is also advancing with the launch of PCSK9 inhibitor ebronucimab and the potential approvals for assets like ebdarokimab and gumokimab. The company is building a dedicated commercial team to tap into the multi-billion RMB metabolic and autoimmune markets. Akeso’s strong pipeline in non-oncology indications will provide additional drivers for sales growth.

Potential Disclosure of Ivonescimab’s Topline HARMONi Clinical Data Mid-Year

International Expansion of Novel Drug Development Accelerates

Akeso’s global partner on ivonescimab, Summit Therapeutics, is advancing three international multicenter Phase III clinical trials:

The HARMONi study, a Phase III clinical trial that evaluates ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a 3rd generation EGFR TKI (e.g., osimertinib). Summit has announced plans to disclose topline data in mid-2025.
Summit expanded the HARMONi-3 study cohort in 2024 to include both squamous NSCLC (sq-NSCLC) and non-squamous NSCLC (nsq-NSCLC), expanding first-line coverage for all NSCLC populations.
The HARMONi-7 study, a global Phase III trial comparing ivonescimab monotherapy with pembrolizumab monotherapy as a first-line treatment for PD-L1-high NSCLC, is expected to begin in 2025.
In February 2025, Summit has entered into a clinical collaboration with Pfizer to evaluate ivonescimab in combination with Pfizer’s antibody-drug conjugates (ADCs) across solid tumors. Pfizer will be responsible for conducting the operations of the studies. The studies will be overseen by both Summit and Pfizer. Both parties retain their respective rights to their products. Akeso is responsible for the production of ivonescimab used in the clinical trial conducted globally.

Beyond bispecific antibodies

Akeso is advancing a pipeline of promising candidates beyond bispecific antibodies. The company’s first self-developed ADC, AK138D1, with the first patient enrolled in Australia for Phase I. Clinical trials for the Company’s first bispecific ADC have also begun. Additionally, the IND application for AK139, the first IL-4Rα/ST2-targeting bispecific, has been accepted.

Ligufalimab (CD47 mAb), considered a key target in immuno-oncology, advanced to Phase III in 2024. A randomized, double-blind, controlled Phase III trial (vs. pembrolizumab) is ongoing for first-line PD-L1(+) head and neck squamous cell carcinoma (HNSCC), making ligufalimab the first CD47 mAb to reach Phase III for solid tumors. A global Phase II trial combining ligufalimab with azacitidine for first-line myelodysplastic syndromes (MDS) is actively progressing across multiple countries, including the U.S.

In parallel with the accelerated global expansion of its novel drug development, Akeso’s therapies and clinical studies have also received recognition in top-tier academic journals and conferences. In 2024, the company revealed nearly 80 groundbreaking research findings in prestigious journals and academic conferences, including JAMA, Nature Medicine, and The Lancet.

On March 30, 2025 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for IBI363, a first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein, as monotherapy for the treatment of unresectable locally advanced or metastatic mucosal or acral melanoma who have not received prior systemic therapy (Press release, Innovent Biologics, MAR 30, 2025, View Source [SID1234651609]).

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Recently, Innovent initiated and dosed the first patient for IBI363 in its first pivotal study to evaluate the efficacy and safety of IBI363 monotherapy versus pembrolizumab (Keytruda) monotherapy in patients with unresectable, locally advanced or metastatic mucosal or acral melanoma who have not received prior systemic therapy. Furthermore, IBI363 has received two fast track designations (FTD) from the U.S. Food and Drug Administration (FDA), for the treatment of squamous non-small cell lung cancer and melanoma, respectively.

IBI363 has demonstrated outstanding efficacy signals in immunotherapy (IO)-naïve melanoma patients across two earlier clinical trials (Phase 1a/1b study NCT05460767 and Phase 2 study NCT06081920), which enrolled a total of 26 patients with advanced acral or mucosal melanoma:

The overall objective response rate (ORR) was 61.5%, and the disease control rate (DCR) was 84.6%—significantly higher than current domestic immunotherapy standards.
Prolonged follow-up revealed sustained tumor responses and long-term benefits, suggesting the potential superiority of IBI363 over existing standard therapies.
Dr. Hui Zhou, Senior Vice President of Innovent, said, "As Innovent’s first-in-class next-generation IO therapy, IBI363 simultaneously and selectively inhibits the PD-1/PD-L1 pathway and activates the IL-2 pathway. IBI363 has recently received multiple FTD and BTD designations, signifying regulatory recognition of its clinical value in addressing unmet medical needs. Non-cutaneous melanoma subtypes like mucosal melanoma—which are more prevalent in China—are particularly resistant to immunotherapy with limited clinical benefits[i]. We aim to validate IBI363’s potential in its first pivotal trial, through a head-to-head comparison with pembrolizumab, as a superior treatment option for melanoma patients over the current standard-of-care. We are also accelerating the global development of IBI363 across multiple tumor types, with the goal of extending the benefits of China’s innovation to patients worldwide."

NMPA Breakthrough Therapy Designation is intended to facilitate and expedite the development and review of investigational drugs for serious diseases or conditions when preliminary clinical evidence indicates substantial improvement over current therapies. BTD qualifies a drug candidate for accelerated review by the CDE and provides the sponsor with timely advice and communication to expedite the approval process, helping to address the unmet clinical needs of patients more swiftly.

About IBI363 (First-in-class PD-1/IL-2α-bias bispecific antibody fusion protein)

IBI363 is a first-in-class drug candidate independently developed by Innovent Biologics. It is a PD-1/IL-2 bispecific antibody fusion protein designed to enhance efficiency while minimizing toxicity. The IL-2 arm of IBI363 has been engineered to optimize therapeutic effects with reduced side effects, while the PD-1 binding arm enables PD-1 blockade and selective IL-2 delivery. By simultaneously inhibiting the PD-1/PD-L1 pathway and activating the IL-2 pathway, IBI363 facilitates more precise and efficient targeting and activation of tumor specific T cells. Preclinical studies have shown that IBI363 exhibits strong anti-tumor activity across multiple tumor-bearing pharmacological models, including those resistant to PD-1 inhibitors and metastatic models. Additionally, it has demonstrated a favorable safety profile in preclinical models.

Clinical trials of IBI363 are currently underway in China, the United States, and Australia to evaluate its safety, tolerability and preliminary efficacy in subjects with advanced malignancies. The first pivotal study of IBI363 has been initiated, for the treatment of IO-naive mucosal or acral melanoma.

Furthermore, IBI363 has received two fast track designations (FTD) from the U.S. FDA, for the treatment of melanoma and squamous NSCLC, respectively. IBI363 has also received breakthrough therapy designation from the NMPA of China for the treatment of melanoma.

About Melanoma

Melanoma is a malignant tumor that develops from melanocytes. Although melanoma accounts for only 3% of all types of skin cancer, it has the highest mortality rate of all types and is the most likely to metastasize. In China, the incidence and mortality rate of melanoma continue to rise. Melanoma is classified into three main subtypes: cutaneous, acral and mucosal. The characteristics of melanoma in Chinese patients differs greatly from those seen in European and American Caucasian populations in terms of pathogenesis, biological behavior, histological morphology, treatment response and prognosis[i]. For advanced cutaneous and acral melanomas, patients with the BRAF V600 mutation typically receive BRAF inhibitor combined with MEK inhibitors as the preferred molecular targeted therapy. For those without the BRAF V600 mutation, chemotherapy combined with anti-angiogenic drugs can be is a first-line treatment option. Notably, pembrolizumab has been approved as the first-line treatment indication for advanced melanoma in September 2024 in China, although clinical benefits are limited. For second-line treatment, therapies not previously used in first-line settings are recommended. Patients who have not received PD-1 monoclonal antibody in the first-line setting may be treated with PD-1 inhibitors as a second-line option. For advanced mucosal melanoma -which are more prevalent in China-are particularly resistant to immunotherapy with limited clinical benefits, in urgent need of new treatment options.