Targeted therapies and antibody drugs enter clinical trials

... beginning the conquest of pancreatic cancer

Onconic Submits IND to initiate a domestic Phase II trial for Nesuparib...“saw positive results in Phase 1 trial”

Companies start developing antibody-drug conjugates and antibody drugs... seek potential for commercialization as combination therapy

Korea’s pharmaceutical and biotech industry is accelerating new drug development for pancreatic cancer, a cancer regarded as one of the most intractable cancers.

 

Onconic Therapeutics, Prestige Biopharma, and Aptamer Sciences have each started clinical trials, making their bid into the field.

 

The company plans to test the commercial viability of various mechanisms in the area, including antibody-drug conjugates (ADCs), targeted anticancer agents, and antibody-based novel therapies.

 

Pancreatic cancer is difficult to detect at an early stage and has a poor prognosis, with a five-year survival rate of only 12.6 percent — the lowest among the nation’s top ten cancers.

 

Given the limited success seen with existing therapies, there is a growing consensus that the development of new drugs is urgently needed.

 

Onconic Therapeutics applies to initate Phase II trial in Korea According to industry sources on the 26th, Onconic Therapeutics has recently submitted an Investigational New Drug (IND) application to the Ministry of Food and Drug Safety for a Phase II clinical trial of its anticancer drug candidate Nesuparib.

 

Nesuparib is a novel drug candidate with a dual mechanism of action, simultaneously inhibiting poly (ADP-ribose) polymerases (PARPs) and tankyrases (TNKS).

 

The compound is currently being evaluated as both a monotherapy and as combination therapy across multiple indications, including pancreatic, endometrial, and gastric cancers.

 

It has also been granted Orphan Drug Designation (ODD) by the U.S.

 

Food and Drug Administration (FDA) for pancreatic and gastric cancers.

 

Onconic Therapeutics has confirmed the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D) for its anticancer candidate in a Phase Ib clinical trial involving patients with advanced or metastatic pancreatic cancer.

 

This multicenter, open-label, Phase Ib dose-escalation study enrolled up to 48 patients with locally advanced or metastatic pancreatic cancer.

 

Participants were divided into two cohorts - Arm A, which received Nesuparib in combination with the FOLFOXIRI regimen (oxaliplatin, leucovorin, irinotecan, and 5-fluorouracil (5-FU)), and Arm B, which received Nesuparib in combination with gemcitabine and nab-paclitaxel.

 

Onconic Therapeutics described the results of the Phase Ib trial as encouraging and announced its intention to present the findings at upcoming major international oncology conferences.

 

New antibody drug development active in the industry… companies also see potential in combination therapies Korea’s pharmaceutical and biotech industry is stepping up its efforts in the field, with companies pursuing a wide range of new drug candidates, including antibody-drug conjugates (ADCs) and novel antibody therapies.

 

Aptamer Sciences recently unveiled preclinical data for its ADC candidate AST-203, which targets TROP2, a protein commonly expressed in breast, pancreatic, gastric, and lung cancers.

 

AST-203 selectively binds to TROP2-positive tumors, penetrates cells, and releases the microtubule inhibitor MMAE to induce tumor cell death.

 

Structurally, AST-203 is composed of an anti-TROP2 antibody linked to the cytotoxic microtubule-inhibiting payload MMAE via a VC-PAB linker.

 

MMAE is the same payload used in Padcev, the ADC therapy developed by Astellas and Seagen.

 

ADC therapy

TROP2 acts as an intracellular calcium signal transducer involved in cell proliferation and survival.

 

Among TROP2-targeting new drugs, only two commercialized products exist: Gilead's ADC Trodelvy and Daiichi Sankyo/AstraZeneca's Datroway.

 

Both products have only secured indications for breast cancer.

 

Because TROP2 is highly expressed in breast, non-small cell lung, colorectal, and pancreatic cancers, the later entrants have been actively conducting clinical studies to tackle such major solid tumors.

 

Aptamer Sciences is leveraging its proprietary ADC platform, “Aptamer,” to address the limitations of conventional ADCs.

 

Aptamers are roughly one-tenth the size of antibodies, enabling deeper penetration into tumor tissue and faster delivery to target cells, enhancing therapeutic efficacy.

 

In preclinical studies using tumor spheroid models (three-dimensional cultured cell aggregates), AST-203 demonstrated a 6.7-fold higher tumor penetration rate compared with Trodelvy.

 

Prestige Biopharma has entered a clinical trial in the U.S for its antibody drug candidate PBP1510.

 

PBP1510neutralizes the PAUF protein, a key driver overexpressed in pancreatic ductal adenocarcinoma (PDAC) that is a major target in pancreatic cancer.

 

Through its Phase I trial, the company aims to assess the safety and tolerability of PBP1510 in combination with gemcitabine.

 

NeoImmuneTech's NT-I7 received FDA orphan drug designation this year for pancreatic cancer.

 

NT-I7 is an anti-cancer drug candidate targeting IL-7, which organizes T-cell development and function, and targets various indications.

 

Immuno-oncology drug

Beyond pancreatic cancer, NT-I7 previously received ODD from the FDA for CD4 lymphopenia (2019), progressive multifocal leukoencephalopathy (2020), and glioblastoma (2023).

 

NeoImmuneTech is currently conducting a Phase II trial evaluating NT-I7 in combination with Keytruda.

 

The trial enrolled 50 patients with previously treated metastatic colorectal cancer and 48 with pancreatic cancer.

 

Interim data showed partial responses (PRs) in three of the 48 pancreatic cancer patients, with a median overall survival (OS) of 11.1 months.