On March 26, 2025 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported its 2024 annual results, including major business updates, financial performance and the strategy and outlook for 2025 and beyond (Press release, Innovent Biologics, MAR 26, 2025, View Source [SID1234651489]).

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Dr. Michael Yu, Founder, Chairman and CEO of Innovent, stated: "2024 marked a year of historic milestones—Innovent’s Non-IFRS net profit and EBITDA both turned positive for the first time, underscoring our strategic excellence and execution as a pioneer in sustainable biopharmaceutical operations. Meanwhile, we achieved record revenue, expanded our robust product portfolio to 15 approved products and delivered all late-stage development milestones to secure sustained growth momentum. We are also advancing breakthrough innovations in our early-stage pipeline for global opportunities while strengthening both global and local partnerships to accelerate innovation and growth.

With a clear strategy outlined above and a strong track record of execution, we are laying a solid foundation to enter a new phase of growth and global innovation. In the coming years, we aim to achieve RMB20bn product revenue in 2027 and advance five pipeline assets to the global MRCT Phase 3 stage by 2030. Through these efforts, we will evolve into a premier global biopharmaceutical company, delivering long-term value for patients, employees, shareholders and society."

Pioneering profitability with RMB20bn sales target in 2027

First-ever Non-IFRS Positive Profit and EBITDA*
Non-IFRS profit was RMB331.6 million and Non-IFRS EBITDA was RMB411.6 million
The gross profit margin was 84.9%, a year-over-year increase of 2.1 percentage points
The S,G&A expenses ratio was 50.9%, a year-over-year decrease of 7.1 percentage points
R&D expenses were RMB2,499.8million; Cash and short-term financial assets were RMB10,221.1 million, or approximately over USD1.4 billion, providing a solid foundation to our long-term ambitions
Revenue reached new height with solidified oncology leadership
Total revenue reached RMB9,421.9 million, growing by 51.8% year-over-year.
Product sales revenue reached RMB8,227.9 million, growing by 43.6% year-over-year.
Expansion of oncology product portfolio with new indications and broader NRDL coverage and patient access
Building CVM commercialization as another core capability
* Note: The financial numbers mentioned above, unless stated, were based on non-IFRS measure. Detailed disclosure can be found at the Company’s 2024 annual results announcement.

Six new product launches in 2025 with growth momentum anticipated
Three additional approved precision therapies to strengthen lung and hematological cancer franchises:
Dovbleron (taletrectinib) : Potentially best-in-class ROS1 inhibitor
Limertinib: Third-generation EGFR TKI
Jaypirca(pirtobrutinib) : First non-covalent BTK inhibitor launched in China
Build chronic disease as another growth engine:
SINTBILO (tafolecimab injection): First PCSK-9 inhibitor successfully included in the NRDL
SYCUME (Teprotumumab N01 injection): First approved anti-IGF-1R monoclonal antibody, ending a 70-year drought of no new treatment options for thyroid eye disease in China；new studies for front-line treatment and inactive thyroid eye disease in plan
Mazdutide (GCG/GLP-1) : Global first GCG/GLP-1 dual receptor agonist, with two NDAs under NMPA review — first NDA for weight management in obese or overweight populations and second NDA for glycemic control of T2D adults. In addition, new Phase 3 studies are in plan for adolescent obesity, obstructive sleep apnea (OSA) and obesity with metabolic dysfunction-associated fatty liver disease (MAFLD, head-to-head with semaglutide 2.4mg). New clinical studies are also in plan for metabolic dysfunction-associated steatohepatitis (MASH), heart failure with preserved ejection fraction (HFpEF), and higher dose of mazdutide for obesity.
Picankibart (IL-23p19): Potentially best-in-class YTE IL-23p19 monoclonal antibody, with an NDA for moderate-to-severe plaque psoriasis under NMPA review. New studies for psoriasis with prior inadequate response to IL-17, adolescent psoriasis, and psoriatic arthritis(PsA) in plan.
2027 RMB20bn sales target with clear growth trajectory
With ever-growing innovative pipeline, sustainable growth is anticipated to continue even beyond 2027
Embarking on a new era of global innovation

Innovent Academy powers core technology platforms
Robust High-potential Pipeline Targeting 5 Assets in MRCT Phase 3 by 2030
Encouraging data readouts of key pipeline in support of next-step pivotal development
IBI363 (PD-1/IL-2α-bias): Unleashing potential as a next-generation IO therapy with global first-in-class design
Promising Phase 1 results reported in NSCLC, CRC and melanoma, aiming to address some of the most challenge cancer types including IO-failed, PD-L1 low expression and cold tumors;
Two Fast-track Designations from U.S. FDA for IO-treated melanoma and IO-treated squamous NSCLC;
First pivotal clinical trial has been initiated, in head-to-head comparison with pembrolizumab in IO-naïve mucosal and acral melanoma.
IBI343 (CLDN18.2 ADC): Novel Site-specific TOPO1i CLDN18.2 ADC
First MRCT Phase 3 of GC has been initiated in China and Japan
MRCT Phase 1 of PDAC is underway in China and U.S.
NMPA CDE Breakthrough Therapy Designation (BTD) and FDA Fast-track Designation (FTD) granted.
Nearly 10 next-generation programs aiming for global development
Oncology: IBI3009 (DLL3 ADC), IBI3001 (EGFR/B7H3 ADC), and IBI3020 (CEACAM5 dual-payload ADC)
CVM: IBI3016（AGT siRNA）, IBI3032（GLP-1 oral）, IBI3012 (GGG Antibody-peptide conjugate, APC), IBI3030（GGG-PCSK9 APC）
Autoimmune: IBI356 (OX40L) and IBI3002 (IL-4Rα/TSLP)
Hybrid models to accelerate innovation
IBI3009 (DLL3 ADC): global rights granted to Roche, to benefit SCLC patients worldwide
Research innovation showcased at medical conferences, including:
AACR, ASCO (Free ASCO Whitepaper), ESMO (Free ESMO Whitepaper) GI, ESMO (Free ESMO Whitepaper) plenary, ESMO (Free ESMO Whitepaper), WCLC, SITC (Free SITC Whitepaper), ESMO (Free ESMO Whitepaper) Asia for oncology pipeline innovation
ADA, APAO, ICE, CSE for general biomedicine pipeline material progress
Facilities and manufacturing capacity adhering to high-quality standards

Shanghai R&D Center (medical) is newly operational in August 2024
Building U.S. lab in San Francisco
First manufacturing site: 60,000L antibody production capacity and ADC production lines in operation
Second manufacturing site: first phase of 80,000L completed construction
Committed to responsible business practices and enhancing ESG management practices

Innovent has been graded ‘AAA’ rating in MSCI ESG rankings, positioning us at the forefront of the biotechnology industry.
We recently launched our ESG website to further strengthen commitment to sustainability, corporate responsibility and ethical business conduct.
We initiated the "Warmth Stations" program to support frontline urban workers (e.g., sanitation workers, delivery personnel), by providing rest areas and essential supplies. Additionally, we launched the third annual "Children’s Book Donation" campaign, bringing hope and support to underprivileged children through book donations.
We have supported over 200,000 patients through our dedicated patient assistance programs, with drug donations totaling RMB 3.6 billion.
Our commitment to medical philanthropy has been recognized through prestigious awards, including the "Medical Philanthropy Promoter" title and designation as a "China Philanthropic Enterprise".
We were recognized on the "2024 China’s Most Attractive Employers List," with a workforce of 7,000 employees.

On March 26, 2024 Alphamab Oncology reported financial results for the full year ended December 31, 2024 and highlighted recent business progress (Press release, Alphamab, MAR 26, 2025, View Source,amounted%20to%20RMB%20159.46%20million. [SID1234654359]).

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Financial Summary

● For the year ended December 31, 2024, we recorded total revenue of RMB 640.08 million, a 192.58% year-on-year increase. Meanwhile, product revenue (attributed to the Company) amounted to RMB 159.46 million.

● For the year ended December 31, 2024, our R&D expenditure amounted to RMB 404.15 million, basically unchanged as compared with prior year.

● For the year ended December 31, 2024, we reached profitability for the first time on an annual basis, recording profit for the year of RMB 166.34 million.

● We have a healthy financial position, with cash reserves of RMB 1,571.47 million as of December 31, 2024.

Business Highlights

With multiple proprietary platforms, the Company has established a globally competitive and differentiated pipeline that includes antibody-drug conjugation (ADC), single domain antibody, and bispecific antibodies. Envafolimab, the world’s first subcutaneously injectable PD-(L)1 inhibitor, was approved by Chinese authorities in 2021, providing a safer and more convenient tumor immunotherapy for patients. Multiple assets are in phase III or pivotal clinical trials, and several other bispecific ADC new drug candidates are in preclinical development.

Commercial Product

KN035 (Envafolimab)

KN035, an innovative anti-tumor immunotherapy drug, is the first subcutaneously injectable PD-(L)1 inhibitor worldwide, the first immunotherapy drug aimed at cross-tumor indications in China and the first domestically produced PD-L1 drug. KN035 offers advantages in effectiveness, safety, convenience and compliance, particularly suitable for frail, elderly patients and those with adverse reactions to intravenous infusions, while significantly reducing the use of healthcare resources.

Events during the Reporting Period

● In January 2024, Envafolimab obtained the market approval by the Pharmaceutical Administration Bureau of the Macau Special Administrative Region of the People’s Republic of China for the treatment of non-metastatic advanced microsatellite instability-high (MSI-H) or non-mismatch-repair deficiency (dMMR) advanced solid tumors.

● In January 2024, Alphamab Oncology and 3D Medicines entered into a license agreement with Glenmark Pharmaceuticals Ltd. (Glenmark) for the subcutaneous injection PD-L1 antibody drug KN035, pursuant to which, Glenmark was granted exclusive licensing interests in clinical development and commercialization of oncology indications of KN035 (the "Field") in India, Asia Pacific (except Singapore, Thailand, Malaysia), the Middle East and Africa, Russia, Commonwealth of Independent States and Latin America (the "Territory"). Glenmark shall bear its own costs and expenses related to the development and commercialization of KN035 in the Field in the Territory. Jiangsu Alphamab retains the exclusive right to produce KN035 for any purpose either inside or outside the Territory.

● In March 2024, Envafolimab was included in the 2024 edition of the "Chinese Expert Consensus on the Use of Immune Checkpoint Inhibitors in Perioperative Treatment of Advanced Gastric Cancer" published by the Gastric Cancer Committee of the Chinese Anti-Cancer Association. Envafolimab has been highly recommended by 16 latest domestic authoritative guidelines and consensus recommendations in 2024.

● In August 2024, Envafolimab was granted breakthrough therapy designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China (NMPA) for the treatment of patients with unresectable or metastatic solid tumors with high tumor mutation burden (TMB-H) who have failed prior standard treatment and no satisfactory alternative treatment.

● In September 2024, the supplementary application for production site, scale and process changes of KN035 successfully passed the GMP compliance inspection, and we received Pharmaceutical GMP Compliance Inspection Certificate in December 2024.

Clinical Product Pipeline

KN026

KN026 is a HER2 heterodimeric bispecific antibody (BsAb) that can simultaneously bind two non-overlapping epitopes of HER2, leading to HER2 signal blockade. KN026 has demonstrated better tumor inhibition in HER2-positive tumor cell lines compared with Trastuzumab and Pertuzumab in combination. Additionally, KN026 has also shown inhibitory effect on tumor cells with Trastuzumab-resistant cell lines. The results of multiple clinical studies in different stages showed that KN026 has significant anti-tumor activities, even in heavily pretreated patients with HER2-positive BC and GC, including those with prior anti-HER2 treatment. KN026 in combination with chemotherapy for the treatment of patients with HER2-positive GC (including GEJ) who have failed first-line standard treatment was granted breakthrough therapy designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China (NMPA).

Events during the Reporting Period

● The phase III clinical trial of KN026 combined with chemotherapy as second-line and later-line treatment of HER2-positive GC/GEJ is undergoing smoothly.

● The phase III clinical trial of KN026 combined with albumin-bound Docetaxel HB1801 as first-line treatment of HER2-positive recurrent and metastatic BC is undergoing smoothly.

● In October 2024, a phase III clinical trial of KN026 in combination with albumin-bound Docetaxel HB1801 was approved by CDE as neoadjuvant treatment for HER2-positive early or locally advanced BC, and the first patient was successfully dosed in December 2024.

Events after the Reporting Period

● In January 2025, the results of phase II clinical trial of KN026 in combination with docetaxel as first-line treatment for HER2-positive recurrent or metastatic BC were published in Cancer Communications.

● In March 2025, the results of phase II clinical trial of KN026 in combination with KN046 for the treatment of advanced HER2-positive solid tumors (excluding BC) were published in Signal Transduction and Targeted Therapy.

JSKN003

JSKN003 is a bispecific ADC developed based on KN026 using the proprietary Glycan-specific conjugation platform. JSKN003 can bind HER2 on the surface of tumor cells and release topoisomerase I inhibitors (TOPIi) through cellular endocytosis, thereby exerting anti-tumor effects. Compared with its ADC counterparts, JSKN003 demonstrated better serum stability and stronger bystander effect, which effectively expands the therapeutic window. Results of multiple clinical studies at various stages of JSKN003 in China and Australia have demonstrated favorable safety profile, with promising efficacy of JSKN003 in heavily pretreated patients with advanced solid tumors, especially in patients with platinum-resistant ovarian cancer (PROC), HER2-expressing BC, or high HER2-expressing solid tumors.

Events during the Reporting Period

● In April 2024, the results of the dose-escalation stage of the phase I clinical trial of JSKN003 conducted in Australia were presented at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which demonstrated favorable tolerability and safety profile of JSKN003 in patients with advanced/metastatic solid tumors who received prior multi-line treatment. The occurrence of hematologic toxicity was very low among common treatment-related adverse events (TRAEs) of all grades and no TRAE led to death or treatment discontinuation. The results also demonstrated encouraging preliminary anti-tumor activity.

● In June 2024, data from a phase I clinical trial of JSKN003 conducted in China were presented for the first time at the 2024 Annual Meeting of American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper). The results showed that the ORR was 51.1% in all efficacy evaluable patients across HER2 low and HER2 positive populations, of which 28 patients who received prior anti-HER2 the ORR was 57.1%, and 21 patients who received prior anti-HER2 ADC the ORR was 57.1%. The results still showed efficacy signals in patients with previous anti-HER2 ADC treatment.

● In September 2024, clinical data from two studies on JSKN003 for the treatment of PROC and HER2-positive (IHC 3+) advanced solid tumors (excluding BC) were presented at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress. The results have demonstrated favorable tolerability and safety profile, with promising efficacy of JSKN003 in heavily pretreated patients with PROC or HER2-positive solid tumors.

● In September 2024, the Company entered a licensing agreement with JMT-Bio Technology Co., Ltd. (JMT-Bio), a wholly-owned subsidiary of CSPC Pharmaceutical Group Co., Ltd. (CSPC) (stock code: 1093.HK), pursuant to which, JMT-Bio was granted 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. Alphamab retains the sole right to supply JSKN003. According to the licensing agreement, Alphamab is entitled to receive upfront payment and milestone payments of up to RMB3.08 billion in total, and a double-digit percentage of royalties on net product sales of JSKN003.

● In December 2024, JSKN003 received approval from CDE to initiate a phase III clinical trial to compare the efficacy of JSKN003 versus investigator-selected chemotherapy for the treatment of platinum-resistant recurrent epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer, and the first patient was successfully dosed in February 2025.

● The phase III clinical trial of JSKN003 for the treatment of unresectable locally advanced or metastatic HER2-low expressing BC is undergoing smoothly.

● Multiple exploratory phase II clinical studies of JSKN003 are currently being conducted.

Events after the Reporting Period

● In February 2025, JSKN003 received approval from CDE to initiate a phase III clinical trial to compare the efficacy and safety of JSKN003 versus trastuzumab emtansine (T-DM1) for the treatment of HER2-positive advanced BC, and the first patient was successfully dosed in the same month.

● In March 2025, JSKN003 was granted breakthrough therapy designation by CDE. The designation is for the treatment of platinum-resistant recurrent epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer, not restricted to HER2 expression levels.

JSKN016

JSKN016 is a bispecific ADC simultaneously targeting HER3 (Human epidermal growth factor receptor 3) and TROP2 (Trophoblast cell surface antigen 2), which is developed with proprietary single-domain antibody platform and Glycan-specific conjugation platform. TROP2 and HER3 are overexpressed in multiple solid tumors. JSKN016 exerts tumor cell-killing activity through dual binding to both antigens, coupled with endocytosis and bystander effects, demonstrating superior efficacy compared to monospecific TROP2 or HER3 ADCs. Furthermore, JSKN016 shows enhanced ability to overcome drug resistance caused by tumor heterogeneity.

Events during the Reporting Period

● In March 2024, JSKN016 received approval from CDE to initiate a phase I clinical trial for the treatment of advanced malignant solid tumors and the first patient was successfully dosed in May 2024. JSKN016 has demonstrated preliminary antitumor activity and a favorable safety profile across multiple solid tumor types, supporting its advancement to the next phase of clinical study.

Events after the Reporting Period

● The phase II clinical trial of JSKN016 monotherapy in multiple subgroups of lung cancer to evaluate efficacy, safety, and dose optimization is currently being conducted.

● The cohort expansion phase clinical trial of JSKN016 monotherapy for the treatment of non-HER2-positive BC is currently being conducted.

● In March 2025, IND application for JSKN016 combined with chemotherapy/immunotherapy /tyrosine kinase inhibitors (TKI) as first-line and later-line treatment of multiple subgroups of non-small cell lung cancer (NSCLC) was approved by CDE.

● In March 2025, IND application for JSKN016 combined with chemotherapy/immunotherapy as first-line and later-line treatment of multiple subgroups of non-HER2-positive BC was approved by CDE.

JSKN033

JSKN033 is a proprietary high-concentration co-formulation consisting of ADC and immune checkpoint inhibitor, independently developed by the Company, which can be administered subcutaneously. JSKN033 is the world’s first subcutaneous injectable ADC for clinical trials. By combining immunotherapy (KN035) and ADC (JSKN003), JSKN033 is anticipated to significantly enhance efficacy while leading to improved safety and convenience.

Events during the Reporting Period

● In March 2024, the first patient has been successfully dosed in Australia in the phase I/II clinical study of JSKN033 for the treatment of HER2-expressing advanced or metastatic solid tumors. The dose escalation phase has been completed until now.

● In November 2024, the research updates of the first-in-human phase I/II clinical trial of JSKN033 for the treatment of HER2-expressing advanced or metastatic solid tumors, have been presented for the first time as a poster in the Late-Breaking Abstract session at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). JSKN033 presented a favorable safety profile and encouraging anti-cancer activity in heavily treated patients.

● In December 2024, JSKN033 received approval from CDE to initiate a phase I/II clinical trial in Chinese patients with advanced metastatic malignant tumors and the first patient was successfully dosed in January 2025. This study has previously been included in the "Pilot Program for Optimizing the Review and Approval of Clinical Trials for Innovative Drugs".

KN046

KN046, a bispecific antibody (BsAb) immune checkpoint inhibitor, composed of a fusion of CTLA-4 and PD-L1 single domain antibody, engineered to target the tumor microenvironment with high PD-L1 expression. Multiple clinical trials of KN046 at different stages covering different types of tumors including non-small cell lung cancer (NSCLC) have been conducted in China, the United States and Australia.

Events during the Reporting Period

● In February 2024, the results of the phase II clinical trial of KN046 in combination with nab-paclitaxel as first-line treatment for advanced triple-negative breast cancer were published in Nature Communications.

● In March 2024, the results of the phase II clinical trial of KN046 in combination with chemotherapy as first-line treatment for metastatic NSCLC were published in Cell Reports Medicine.

● In August 2024, the results of phase Ib clinical trial of KN046 in combination with chemotherapy and palliative radiotherapy as first-line treatment for advanced esophageal squamous cell carcinoma were published in Cancer Immunology, Immunotherapy.

● In September 2024, we completed OS final analysis for a phase III clinical trial of KN046 for the treatment of advanced squamous NSCLC (sq NSCLC).

● In December 2024, the results of the phase II clinical trial of KN046 in combination with Axitinib as first-line treatment for advanced NSCLC were presented at the European Society for Medical Oncology Immuno-Oncology (ESMO IO) Congress 2024.

Events after the Reporting Period

● In February 2025, the results of phase II clinical trial of KN046 in combination with lenvatinib for the treatment of advanced unresectable or metastatic hepatocellular carcinoma were published in Nature Communications.

Early-stage R&D

Leveraging proprietary platform technologies including glycan-specific conjugation, linker-payload, dual-payload conjugation, and bispecific antibodies, the Company has developed globally competitive new drugs such as ADCs and bispecific antibodies. The bispecific ADCs (BADC) and dual-drug conjugates (BADDC) developed by the Company, not only improve tumor targeting but also address heterogeneity and resistance issues, offering new strategies for cancer treatment. Currently multiple innovative bispecific ADC new drug candidates are in preclinical development and will be advanced into clinical trials sequentially.

● In June 2024, Jiangsu Alphamab entered into a research and collaboration agreement with ArriVent BioPharma, Inc. to use Jiangsu Alphamab’s proprietary linker-payload (Alphatecan) and glycan-specific conjugation platforms to discover and develop novel bispecific ADCs.

Manufacturing Facilities

The Company’s manufacturing facility was constructed in compliance with Good Manufacturing Practice (GMP) standards of the National Medical Products Administration of China (NMPA), the U.S. Food and Drug Administration (FDA), and the European Medicines Agency (EMA). The production lines are equipped with world-class equipment capable of meeting the large-scale manufacturing needs for a variety of biologics, including ADCs, both in the clinical and commercial stages. In 2024, the Company further expanded its production capacity by constructing the new suite dedicated to ADC drugs, which will be put into operation soon.

Other Highlights

● In November 2024, the Company was granted "2024 Top 100 Chinese Pharmaceutical Innovative Enterprises"and"2024 China Pharmaceutical Innovative Enterprise Bispecific Antibody Track Top5"by Healthcare Executive, a specialized magazine focusing on the pharmaceutical industry.

● In November 2024, the Company was granted "2024 Top 100 Brand Influence of Chinese Pharmaceutical Enterprise" by the China Health Culture Association, the China Hospital Association, and the National Health Commission of the People’s Republic of China Health TV Channel (CHTV) at the 2024 Healthy China Communication Conference.

For more information, please refer to the Company’s Annual Results Announcement for the Year Ended December 31, 2024 published on the Hong Kong Stock Exchange and the Company’s official website.

On March 26, 2025 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that its research collaborators will present at the upcoming 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 25-30, 2025 in Chicago, Illinois (Press release, Genprex, MAR 26, 2025, View Source [SID1234651458]). The collaborators will present positive preclinical data from a study of its lead drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid), for the treatment of KRASG12C mutant non-small cell lung cancer (NSCLC).

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"We are delighted to have our academic partners present positive preclinical data on our lead drug candidate, REQORSA, as a potential therapeutic treatment for Ras inhibitor resistant lung cancer," said Ryan Confer, President and Chief Executive Officer at Genprex. "These preclinical data further validate REQORSA as a potential treatment for many types of cancer, including another subset of lung cancer. We remain highly encouraged by the role that TUSC2 plays in the treatment of lung cancer and by our preclinical programs expanding on the potential use of REQORSA to treat many types of cancer where patient populations continue to have unmet medical needs."

The featured Genprex-supported poster to be presented at AACR (Free AACR Whitepaper) 2025:

Title: Overcoming sotorasib acquired resistance in KRASG12C mutant NSCLC by TUSC2 gene therapy

Session Category: Experimental and Molecular Therapeutics

Session Title: Drug Resistance in Molecular Targeted Therapies 3

Session Date and Time: Tuesday, April 29 from 2-5 p.m. CT

Location: Poster Section 17

Poster Board Number: 12

Abstract Presentation Number: 5517

The featured Genprex-supported abstract to be presented at AACR (Free AACR Whitepaper) 2025:

Acquired resistance (AR) to Lumakras (sotorasib), the first FDA-approved KRASi, poses a significant challenge in the treatment of KRASG12C mutant NSCLC. Despite initial responses, patients invariably develop resistance, necessitating alternative therapeutic strategies. The mechanisms underlying AR include the emergence of additional mutations in the KRAS gene, reactivation of the KRAS pathway, or activation of alternative signaling pathways. TUSC2, a potent tumor suppressor gene with immunogenic properties, exhibits multifunctional activity by inhibiting downstream signaling pathways, including MAPK and mTOR; arresting the growth and proliferation of cancer cells; inducing tumor cell death; and activating innate and adaptive immune responses. In this study, researchers demonstrated that TUSC2 gene therapy (REQORSA) effectively overcomes sotorasib AR in KRASG12C mutant NSCLC mouse xenografts.

The data indicate that TUSC2 transfection significantly reduced colony formation in two AR cell lines. Transfection of TUSC2 also markedly increased apoptosis in AR cells. Re-expression of TUSC2 into AR PDXOs significantly decreased the viability of organoids compared with the empty vector. The H23AR tumors exhibited significantly lower sensitivity to sotorasib than their parental counterparts. However, treatment with REQORSA was highly effective in controlling tumor growth compared to treatment with sotorasib alone or the control groups. REQORSA alone also exhibited a strong antitumor effect on TC314AR PDXs. Sotorasib alone showed no significant antitumor activity in these models. However, a synergistic antitumor effect was observed when TC314AR PDX tumors were treated with the combination of REQORSA and sotorasib.

In conclusion, researchers demonstrated that REQORSA, alone or in combination with sotorasib, induced apoptosis, inhibited colony formation, and showed significant antitumor efficacy in KRASG12C mutant sotorasib-acquired resistant xenograft and PDX tumors.

About Reqorsa Gene Therapy

REQORSA (quaratusugene ozeplasmid) consists of a plasmid containing the TUSC2 gene encapsulated in non-viral lipid-based nanoparticles in a lipoplex form (the Company’s Oncoprex Delivery System), which has a positive charge. REQORSA is injected intravenously and specifically targets cancer cells. REQORSA is designed to deliver the functioning TUSC2 gene to negatively charged cancer cells while minimizing uptake by normal tissue. Laboratory studies conducted at MD Anderson show that the uptake of TUSC2 in tumor cells in vitro after REQORSA treatment was 10 to 33 times the uptake in normal cells.

On March 26, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, reported it will be presenting a business update today at Trump Mar-a-Lago Club, Florida (Press release, Actinium Pharmaceuticals, MAR 26, 2025, View Source [SID1234651474]). This presentation follows an Investor KOL Call and Company Update hosted by Actinium on Tuesday, March 25th highlighting its revitalized clinical programs and expanded market opportunities.

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Sandesh Seth, Actinium’s Chairman and CEO, said, "We are honored to have this opportunity to present Actinium Pharmaceuticals and highlight the significant progress we have made in the last several months at the Mar-a-Lago Club. We have great enthusiasm for our revamped clinical programs and expect to achieve significant milestones in 2025. If successful, we will have the opportunity to address multiple potential blockbuster market opportunities with Actimab-A in myeloid malignancies and solid tumors and with Iomab-ACT for cell and gene therapy conditioning."

Actinium has outlined its expanded market opportunities and expected 2025 milestones for each of its clinical programs as well as its R&D and radiopharmaceutical manufacturing capabilities as follows:

Actimab-A as a mutation agnostic, backbone therapy for myeloid malignancies including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) across multiple treatment settings

Initiate Phase 2/3 trial in combination with CLAG-M in relapsed or refractory AML and seek potential partners or collaborators
Generate initial clinical data in frontline AML in first trial under CRADA with NCI
Initiate additional clinical trials in myeloid malignancies
Actimab-A as a pan solid tumor therapy in combination with PD-1 inhibitors including KEYTRUDA and OPDIVO by depleting myeloid derived suppressor cells (MDSCs)

Generate clinical proof of concept data in head and neck squamous cell carcinoma and non-small cell lung cancer
Explore additional solid tumor indications for future trials
Iomab-ACT as a universal targeted conditioning agent to increase patients access to cell & gene therapies and improve patient outcomes

Present initial data from commercial CAR-T trial at University of Texas Southwestern
Generate clinical data in first non-malignant indication from sickle cell disease allogeneic stem cell transplant trial at Columbia University
Pipeline Expansion Leveraging Targeted Radiotherapy R&D Capabilities

Present abstract at AACR (Free AACR Whitepaper) highlighting Actinium-225 targeted radiotherapy for novel radiotherapy cancer target
Establish In-house Radiopharmaceutical Manufacturing & Production

Advance build-out of manufacturing facility
Explore strategic partnerships leveraging proprietary Actinium-225 cyclotron manufacturing technology
Mr. Seth continued, "In addition to the multitude of milestones that lie ahead for our clinical programs, we are excited to highlight our expanding capabilities. As a pioneer in targeted radiotherapy, we are leveraging our robust know-how and intellectual property to develop new pipeline programs to address indications with high unmet needs. In addition, we are investing in our infrastructure and are thrilled to be moving ahead with the build-out of our manufacturing facility starting next quarter in anticipation of future clinical success. Finally, we look forward to fully leveraging our proprietary Actinium-225 cyclotron manufacturing technology to meet our projected demand given our expanding Actinium-225 programs as well as facilitate strategic partnerships. With our strong balance sheet providing runway into mid-2027, our team is focused and committed on execution and value creation."

On March 26, 2025 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for hematologic malignancies and solid tumors, reported that it will release results from four preclinical studies in poster presentations at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (AACR 2025), taking place from April 25th to 30th at the McCormick Place Convention Center, Chicago, the United States (Press release, Antengene, MAR 26, 2025, View Source [SID1234651490]). These four posters will feature Antengene’s four highly differentiated and high-potential programs, including ATG-201 (CD19 x CD3 TCE) and ATG-042 (MTAPnull-selective PRMT5 Inhibitor), which are poised to enter clinical development in the second half of 2025; ATG-110 (LY6G6D x CD3 TCE), which was developed on the AnTenGagerTM TCE 2.0 platform for the treatment of microsatellite stable colorectal cancer; and a companion diagnostic antibody developed to assess CD24 expression and guide clinical studies of CD24-targeted therapies.

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Details of the Poster Presentation:
ATG-201 (CD19 x CD3 T cell engager)
Title: ATG-201, a novel T-cell engager (TCE) effectively depletes B cells with reduced risk of CRS for the treatment of B cell malignancies and B cell related autoimmune diseases
Abstract Number: 7326
Session Category: Immunology
Session Title: T Cell Engagers and Novel Antibody-Based Therapies
Date: April 30, 2025
Time: 9:00 AM – 12:00 PM (Central Time)
10:00 PM, April 30, 2025 – 1:00 AM, May 1, 2025 (Beijing Time)
Location: Poster Section 40

Introduction: By depleting autoreactive B cells, CD19-targeted CAR-T have shown early yet promising efficacy in treating patients with B cell-driven autoimmune diseases. However, the clinical application of TCE continues to be greatly hindered by the unfavorable pharmacokinetics and toxicity associated with cytokine release syndrome. To overcome these limitations, Antengene developed ATG-201, a "2+1" CD19 x CD3 TCE, which was evaluated in a series of in vitro studies for binding affinity, T cell dependent cytotoxicity (TDCC) cytokine release, and drug developability. The in vivo anti-lymphoma efficacy and pharmacodynamic effect were evaluated in Raji xenograft model. The tissue resident B cell depletion was assessed in CD34+ hematopoietic stem cells humanized mice. Pharmacokinetic parameters of ATG-201 were evaluated in normal Balb/c mice.
Results: Compared to benchmark TCEs, ATG-201 demonstrated stronger naïve B cell depletion activity with much lower cytokine release in vitro. ATG-201 showed potent anti-lymphoma activity in PBMC-humanized subcutaneous Raji xenograft model with significant augment of infiltrated CD8+ T cells in tumor microenvironment and limited proinflammatory cytokines detected in plasma. Single dose ATG-201 completely and deeply depleted B cells in blood, bone marrow and spleen of CD34+ cells humanized mice. ATG-201 demonstrated potent efficacy in mouse systemic lupus erythematosus model, inhibiting the lymph node swelling and auto-antibody producing.
Conclusions: ATG-201 demonstrated CD19-dependent CD3 binding and activation, inducing effective B cell depletion in vitro and in vivo with low cytokine release, which provides potential for the treatment of B cell malignancies and B cell related autoimmune diseases. ATG-201 is poised to enter clinical development in the second half of 2025.
ATG-042 (MTAPnull-selective PRMT5 Inhibitor)
Title: Preclinical characterization of ATG-042, a novel MTAPnull-selective PRMT5 inhibitor
Abstract Number: 4230
Session Category: Experimental and Molecular Therapeutics
Session Title: HDAC and Methyltransferase Inhibitors
Date: April 29, 2025
Time: 9:00 AM – 12:00 PM (Central Time)
10:00 PM, April 29, 2025 – 1:00 AM, April 30, 2025 (Beijing Time)
Location: Poster Section 16

Introduction: Targeting the PRMT5-MTA complex has become a promising strategy for treating MTAPnull cancer in a synthetically lethal manner, avoiding on-target off-tumor hematological toxicity when using first-generation, non-selective PRMT5 inhibitors. Herein, Antengene developed ATG-042, a novel MTAPnull-selective PRMT5 small molecule inhibitor with good brain penetration. In this study, the in vitro activity and MTAP selectivity of ATG-042 were profiled using HCT116 MTAP wild type (wt) cells, HCT116 MTAP knock out (ko) cells and multiple endogenous MTAPnull cell lines. The in vivo efficacy was tested in cell derived xenograft (CDX) mouse models with HCT116 MTAP wt cells, HCT116 MTAP ko cells, LU99 cells (MTAPnull) and U87MG-luc (MTAPnull). The pharmacokinetic and toxicological properties were assessed with corresponding assay methods.
Results: ATG-042 showed excellent anti-proliferative activities on multiple endogenous MTAPnull cell lines with IC50 values between 10nM and 100nM. ATG-042 demonstrated high permeability, good metabolic stability, and low risk of drug-drug interaction. In vivo PK study shows that ATG-042 is well absorbed, with a dose-dependent increase in plasma distribution and high oral bioavailability in mice, SD rats and beagle dogs. Furthermore, ATG-042 is brain-penetrable (B/P ratio=51% in mice; KPuubrain=0.73 in rats). ATG-042 showed robust in vivo efficacy in both subcutaneous CDX models (HCT116 -MTAP ko, LU99) and orthotopic CDX model (U87MG-luc) as a single agent. In addition, ATG-042 also exhibited potential synergy in combination with other drugs for antitumor therapy.
Conclusions: ATG-042 is an oral MTAPnull-selective PRMT5 inhibitor with potent efficacy against MTAPnull tumor. It also demonstrated good tolerability and brain penetrability. ATG-042 is poised to enter clinical development in the second half of 2025.
ATG-110 (LY6G6D x CD3 T cell engager)
Title: ATG-110, a novel "2+1" LY6G6D-targeted T-cell engager (TCE) for the treatment of MSS colorectal cancer
Abstract Number: 3509
Session Category: Immunology
Session Title: T Cell Engagers
Date: April 28, 2025
Time: 2:00 PM – 5:00 PM (Central Time)
3:00 AM – 6:00 AM, April 29, 2025 (Beijing Time)
Location: Poster Section 38

Introduction: Colorectal cancer (CRC) is one of the most common cancers worldwide and requires more effective and safer therapies to improve the poor survival outcome, particularly in patients with microsatellite stable (MSS) colorectal cancer, who exhibit primary resistance to immune checkpoint inhibitors and lack effective treatment options. T cell engagers have shown encouraging efficacy in treating hematological malignancies, while exhibiting suboptimal clinical efficacies in solid tumors. The risk of cytokine release syndrome (CRS) remains as a significant challenge clinically. ATG-110 is a novel "2+1" LY6G6D x CD3 TCE developed by Antengene. In this study, ATG-110 was evaluated in a series of preclinical in vitro studies for binding affinity, T cell activation and cytokine release, T cell dependent cytotoxicity (TDCC), and drug developability. The in vivo anti-tumor efficacy was evaluated in PBMC-humanized immunodeficient NDG mice engrafted with LY6G6Dmedium-expression HT55 or LY6G6Dvery low-expression SW480 MSS CRC cells.
Results: ATG-110 binds to LY6G6D-positive cell lines, including LY6G6D-overexpression 293T, HT55, LS1034, with the nanomolar grade EC50. The CD3 binding site of ATG-110 is concealed by the LY6G6D Fab arm before binding to LY6G6D, due to the steric hindrance. Therefore, ATG-110 demonstrated limited binding capability to CD3+ cells before LY6G6D crosslinking. It activates T cells and induces cytokine release only in the presence of LY6G6D+ cells. In vitro, ATG-110 resulted in potent T cell dependent cytotoxicity with single-digit pM IC50 values on HT55 and SW480 cells. ATG-110 also showed potent anti-tumor activity in PBMC-humanized SW480 xenograft model and exhibited complete response (CR) in PBMC-humanized HT55 xenograft model. Furthermore, ATG-110 also demonstrated good drug developability.
Conclusions: ATG-110 demonstrated LY6G6D-dependent CD3 binding and activation with low risk of CRS. It showed powerful in vitro and in vivo anti-tumor efficacy against colorectal cancer, which warrants further clinical evaluation.
ATG1144 (CD24 CDx Antibody)
Title: Development of a diagnostic antibody for CD24 targeted therapy
Abstract Number: 671
Session Category: Clinical Research
Session Title: Diagnostic Biomarkers 2
Date: April 27, 2025
Time: 2:00 PM – 5:00 PM (Central Time)
3:00 AM – 6:00 AM, April 28, 2025 (Beijing Time)
Location: Poster Section 29

Introduction: CD24 has emerged as a promising therapeutic target for anti-cancer treatment. Several clinical trials are being conducted to evaluate the safety and efficacy of CD24-targeted therapies. Here, Antengene developed and characterized an anti-CD24 diagnostic antibody to enhance the screening and selection of patients based on CD24 expression. In this study, the authors described the discovery of the diagnostic antibody, and the evaluation of accuracy, sensitivity (selectivity), specificity, and assay precision of the antibody.
Results: Monoclonal antibody clone ATG1144 binds to the hCD24 core peptide in ELISA with an EC50 of 0.06 nM. Distinct membrane staining on human normal esophageal tissue FFPE specimens can also be observed with IHC staining using ATG1144. For accuracy assessment, six CDX and twenty human specimens, comprising both positive and negative specimens (including solid tumors and B-cell non-Hodgkin lymphomas), were validated. Samples exhibiting high, medium, and low CD24 expression levels were evaluated for sensitivity and specificity, and the interpreted results aligned with the reference outcomes. FFPE tissues from three distinct patients were evaluated for assay precision assessment. The TMA IHC staining result revealed that 50-80% of patients with lung, breast, bladder, ovarian, or liver cancer have CD24 expression on tumor cell surface with low expression in the para-cancerous normal tissue.
Conclusions: ATG1144 specifically binds to human CD24 with high sensitivity as demonstrated by IHC staining. The development and validation of the method have been finalized using Leica Bond III platforms. These data suggest a potential diagnostic use of ATG1144 for identifying CD24+ patients.