Dato-DXd (datopotamab deruxtecan), jointly developed by Daiichi Sankyo and AstraZeneca, and NTLA-2001, co-developed by Intellia Therapeutics and Regeneron Pharmaceuticals, were evaluated to have high potential value among new drugs whose clinical results will come out this year.

Kwak Seo-yeon, a senior fellow at the Korea Drug Development Fund, predicted the two drugs as Nos. 1 and 2 in net current value among substances with their clinical results expected to come out this year in a report, “Top-10 R&D Project for Global New Drug Development in 2023,” released on Monday.

The pipeline with the highest net present value was Dato-DXd, with $9.6 billion.

Dato-DXd is an antibody-drug conjugate that targets TROP2. More than 10 clinical trials are currently conducted on cancerous tumors expressing TROP2, including breast and lung cancer.

Dato-DXd typically stands out in the combination therapy of durvalumab (product name: Imfinzi) and pembrolizumab (product name: Keytruda).

Through the follow-up results of 3.9 months in phase 1b/2 clinical trials, called the BEGONIA study, in 2022, the combo therapy with durvalumab showed the objective response rate (ORR) of 73.6 percent, complete response (CR) of 8 percent, and partial response (PR) of 67 percent, confirming treatment efficacy. Regarding safety, there were no dose-limited toxic reactions, and the rate of discontinuation of clinical trials due to adverse reactions was 7 percent.

Also, according to the TROPIOC-Lung02 Study, a clinical trial on combination therapy with pembrolizumab presented at World Conference on Lung Cancer (WLCLC) in August 2022, the Dato-DXd and pembrolizumab combo therapy as the primary treatment for non-small cell lung cancer (NSCLC) showed treatment efficacy and drug tolerance equivalent to ORR of 62 percent, PR of 62 percent, and disease control rate of (DCR) of 100 percent.

However, in the side effects of interstitial lung disease (ILD) observed in the DXd-ADC family, two third-degree ILDs occurred, indicating that they were not free from side effects. Therefore, clinical trials related to safety will be conducted in the future.

The medical product with the second highest net present value was NTLA-2001, valued at $6.3 billion. NTLA-2001 is a treatment candidate for transthyretin amyloid (ATTR). It recognizes a specific sequence and injects a Cas9 enzyme protein into the vein that cuts the DNA at the site, permanently deactivating the abnormal transthyretin (TTR) gene in the hepatocytes. It is a CRISPR/Cas9 gene editing treatment designed to reduce the accumulation of proteins in TTR.

In 2022, Intellia and Regeneron announced interim analysis results of phase 1 clinical trials that evaluated drug tolerance, safety, and PK/PD depending on doses of NTLA-2001 in patients with ATTR with polyneuropathy (PN) and ATTR with cardiomyopathy (CM).

In seven cohort groups – four ATTR-PN and three ATTR-CM – conducted by different patient groups and administrative doses, NTLA-2001 groups showed TTR reducing the effect of a maximum of 94 percent on the 28th day and confirmed similar TTR-reducing effect in the long-term follow-up results of six months or more.

NTLA-2001 also draws attention as the first ATTR monotherapy candidate. Among drugs approved by the U.S. Food and Drug Administration as the ATTR treatment, vutrisiran (product name: Amvuttra) has received the highest mark for administrative convenience, featuring a method of subcutaneous administration (SA) once every three months and four times a year.

NTLA-2001 is a product developed jointly as part of genetic treatments using CRISPR gene-editing technology by Intellia and Regeneron since April 2016. In 2020, Regeneron secured the right to commercialize NTLA-2001 through an additional license contract worth $100 million.