K-pharma unveils results on TPD to ADC at AACR

Results from preclinical trials, such as TPD, will be unveiled

Korean companies are developing innovative new drugs and best-in-class drugs…demonstrated potential for patients with drug tolerance

The Korean pharmaceutical and biotech industry has shown achievements in developing anticancer drugs equipped with novel mechanisms.

 

They demonstrated potential in areas that have rapidly risen as R&D trends, such as targeted protein degraders, antibody-drug conjugates (ADCs), and bispecific antibodies.

 

According to industry sources on the 29th, the American Association for Cancer Research Annual Meeting (AACR 2025) began on the 25th and will run for five days in Chicago, USA.

 

The AACR is classified as one of the world’s top three oncology conferences, along with the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO).

 

The annual meeting primarily features early‐stage clinical results for anticancer drug candidates, such as preclinical and phase 1 data.

 

Dong-A ST·Therapex demonstrated achievements in preclinical trials involving TPD Companies such as Dong-A ST, Therapex, Pin Therapeutics, and Nibec unveiled their development results for targeted protein degraders (TPDs) at this meeting.

 

While conventional small‐molecule therapies inhibit protein function, TPD drugs are designed to fundamentally degrade and remove disease-causing proteins, offering superior therapeutic efficacy and eliminating resistance issues.

 

TPD drugs's advantage lies in their ability to target over 80 % of disease-causing proteins that cannot be modulated by conventional small‐molecule compounds.

 

Dong-A ST unveiled preclinical results for its EGFR-targeted protein degrader 'SC2073' at this meeting.

 

Currently available EGFR-positive lung cancer treatments include first-generation Iressa (gefitinib, AstraZeneca) and Tarceva (erlotinib, Roche), second-generation Giotrif (afatinib, Boehringer Ingelheim) and Vizimpro (dacomitinib, Pfizer), and third-generation Leclaza (lazertinib, Yuhan) and Tagrisso (osimertinib, AstraZeneca).

 

However, resistance often develops even with highly effective targeted therapies.

 

The C797S mutation is a key resistance mechanism in EGFR-positive treatment.

 

Moreover, treatment options remain limited after resistance to targeted therapies emerges.

 

For patients with resistance to targeted therapies, options such as platinum-based chemotherapy, docetaxel, or immuno-oncology agents are available, but response rates show no significant improvement.

 

SC2073 acts on an allosteric binding site of EGFR and selectively degrades only the mutant EGFR forms that are resistant to existing non-small cell lung cancer (NSCLC) therapies.

 

It does not affect normal EGFR, thereby minimizing associated side effects.

 

Therapex unveiled data on its degrader antibody–drug conjugate (DAC) 'TRX-214-1002,' which links a GSPT1 molecular glue to a CD33 antibody, at AACR 2025.

 

DACs are expected to offer higher safety than ADCs because they employ TPDs, small molecules that degrade proteins.

 

ADCs are novel anticancer drugs that connect an antibody, which binds to specific antigens on the surface of cancer cells, with a cytotoxic drug linked by a linker.

 

ADCs use antibodies' selectivity for their targets and the drug's cytotoxic activity to selectively target cancer cells, thereby increasing therapeutic efficacy while minimizing side effects.

 

While Roche's Kadcyla, the first-generation ADC, is only approved for breast cancer, second-generation ADCs are approved for various indications.

 

Enhertu and Trodelvy have been shown to be effective in various solid cancer areas, such as breast cancer, non-small cell lung cancer (NSCLC), and colorectal cancer.

 

Despite its high intracellular target specificity and ability to induce decreased protein expression, TPD has low in vivo utilization.

 

Developers are conducting clinical trials to use TPD and ADC for precise target identification.

 

AACR 2025

Therapex is developing TRX-214-1002 as a treatment for acute myeloid leukemia (AML) that is refractory to existing therapies or has low drug responsiveness.

 

In July of last year, it received support from the Korea Drug Development Fund (KDDF) to advance its development.

 

TRX-214-1002 attaches a GSPT1 payload to the same antibody used in the ADC therapeutic 'Mylotarg.' Preclinical results showed that TRX-214-1002 demonstrated improved outcomes in AML treatment compared with conventional ADC therapies.

 

Pin Therapeutics has unveiled the preclinical research results for 'PIN-5018' for the first time.

 

PIN-5018 is a molecular glue degrader targeting CK1α (Casein Kinase 1 alpha), operating via a mechanism that blocks cancer cell survival pathways.

 

Pin Therapeutics has unveiled the preclinical research results for 'PIN-5018' for the first time.

 

PIN-5018 is a molecular glue degrader targeting CK1α (Casein Kinase 1 alpha), operating via a mechanism that blocks cancer cell survival pathways.

 

CK1α is a serine/threonine kinase that plays essential roles in cell cycle regulation, DNA repair, immune responses, and other vital functions.

 

PIN-5018 works by suppressing cancer cell growth and survival through induction of the degradation of this protein.

 

PIN-5018 is being developed specifically for MSS (Microsatellite Stable) colorectal cancer, which has a low response rate to immuno-oncology drugs.

 

MSS-type colorectal cancer accounts for approximately 80–85% of all colorectal cancers.

 

Still, it is classified as an area of high unmet need because current response rates to immuno-oncology drugs or targeted therapies are low, and the duration of response is short.

 

Pin Therapeutics reported that PIN-5018 demonstrated superior antitumor efficacy compared to existing first-line therapies in preclinical studies and showed positive potential as a monotherapy and in combination regimens.

 

Yuhan·Celltrion·Aptamer Sciences presented preclinical results for ADCs and bispecific antibodies Yuhan and ABL Bio presented preclinical data on 'YH32364' (ABL104) in a poster session at this AACR meeting.

 

YH32364 is designed as a bispecific antibody that simultaneously targets EGFR and 4-1BB.

 

EGFR is a well-known biomarker expressed in major solid tumors, including non–small cell lung cancer (NSCLC) and colorectal cancer.

 

By simultaneously targeting EGFR and T-cell activating 4-1BB, Yuhan aims to maximize the antitumor effect of this immuno-oncology candidate.

 

Yuhan reported that in a preclinical efficacy trial, YH32364 showed stronger superior effects in EGFR-expressing tumors compared to cetuximab.

 

It was demonstrated that the candidate drug retained long-term anti-tumor effects through immunological memory.

 

Furthermore, it was confirmed that YH32364 activated 4-1BB signaling in EGFR-expressing tumors, leading to the recruitment of tumor-infiltrating immune cells and altering the tumor microenvironment.

 

Cetuximab is an anticancer agent that targets the EGFR receptor and is used to treat various cancers, including colorectal cancer, head and neck cancer, and lung cancer.

 

It is particularly well known to be effective in colorectal cancer patients with KRAS gene mutations.

 

Yuhan stated that YH32364 works by activating immune cells through EGFR-specific 4-1BB signaling in tumors.

 

The company hopes YH32364 will be more effective in a wide variety of EGFR-expressing solid cancers than anti-EGFR mAb.

 

AACR 2025

Celltrion presented preclinical results for its multi-specific antibody-based anticancer drug candidate, 'CT-P72.' CT-P72 is a multi-specific antibody immunotherapy co-developed by Celltrion and Abpro, a biotechnology company based in the United States.

 

This therapy is designed as a T-cell engager (TCE), which connects cancer cells that express HER2 (Human Epidermal Growth Factor Receptor 2) with T cells, a type of immune cell, to help eliminate the cancer cells.

 

T-cell engagers are a bispecific antibody-based modality that physically links cancer cells and immune cells to treat cancer.

 

This mechanism can harness the human immune system to attack cancer, enabling more precise targeting of cancer cells and eliciting a potent immune response.

 

CT-P72 is designed to simultaneously target HER2 and the immune cell surface protein CD3 to activate T cells and attack cancer cells while minimizing toxicity to normal cells.

 

In particular, it demonstrated high tumor inhibition by selectively acting on cancer cells in HER2-overexpressing tumor models.

 

Moreover, CT-P72 consistently maintained its antitumor efficacy in both in vitro and in vivo studies, and in primate toxicity tests, it exhibited 180-fold superior safety compared to a reference compound.

 

Aptamer Sciences presented pre-clinical results of its new ADC candidate product, 'AST-203.' AST-203 targets the protein TROP2, which is predominantly expressed in breast, pancreatic, gastric, and lung cancers.

 

This drug candidate binds selectively to TROP2-positive tumors, penetrates the cells, and releases the microtubule inhibitor MMAE to induce cancer cell death.

 

AST-203 is made by conjugating TROP2-targeting antibody with 'MMAE,' a microtubule disruption agent, with linker 'VC-PAB.' TROP2 is an intracellular calcium signal transducer involved in cell proliferation and survival.

 

Among TROP2-targeting drugs, the commercialized products are Gilead's ADC Trodelvy and Daiichi Sankyo/AstraZeneca's Datroway.

 

Both products are approved for breast cancer indications only.

 

Because TROP2 is mainly found in breast cancer, NSCLC, colorectal cancer, and pancreatic cancer, later entrants are conducting clinical trials targeting these major solid tumors.

 

Aptamer Sciences is exploring ways to overcome the limitations of existing ADC therapies using its proprietary ADC platform technology, 'Aptamer.' Aptamers are one-tenth the size of antibodies, allowing deeper penetration into tumor tissue and rapid delivery to target cells for therapeutic effect.

 

In preclinical studies, Aptamer Sciences confirmed the potential of AST-203 in tumor spheroid models (three-dimensional aggregates of cultured cells).

 

According to the company, AST-203 demonstrated a 6.7-fold higher tumor penetration rate than Trodelvy.