Nutcracker Therapeutics Showcases NTX-472's Enhanced B Cell Lymphoma Activity at 2024 ASCO

Nutcracker Therapeutics, Inc., a biotechnology company based in Emeryville, California, is pioneering the development of innovative RNA therapies. Recently, they showcased NTX-472, a promising preclinical drug candidate aimed at treating B cell lymphoma, at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. This new candidate has garnered attention due to its unique approach to targeting cancer cells.

Traditional monoclonal antibody immunotherapies have been effective in treating B cell lymphoma by targeting specific tumor antigens, such as CD19 or CD20. However, these therapies often face challenges as cancer cells can adapt by down-regulating the expression of the targeted antigens, making them invisible to the immune system. This can result in the tumors becoming resistant to the treatment, known as "cold tumors."

To address this issue, Nutcracker Therapeutics has developed a multispecific antibody, NTX-472, which targets multiple antigens simultaneously. Their scientists engineered molecules that can engage CD20, CD19, and CD47 at the same time. By doing so, they aim to enhance the specificity and efficacy of the treatment, reducing the likelihood of the tumor evading the immune system. In vitro studies identified NTX-472 as having superior tumor-killing abilities and B cell depletion compared to existing monoclonal antibody treatments like rituximab and tafasitamab.

Further in vivo studies using Nutcracker Therapeutics' proprietary CodonCrackerTM software and the Nutcracker® Manufacturing Unit showed promising results. In cynomolgus monkeys, a single dose of NTX-472 rapidly depleted B cells without any detectable binding to red blood cells. This is a significant finding, as it suggests that NTX-472 could be both an effective and safer treatment option for B cell lymphoma.

Chief Scientific Officer Samuel Deutsch, Ph.D., expressed pride in the company's achievements, highlighting that Nutcracker Therapeutics is among the first RNA therapeutics companies to engineer a multispecific antibody. He noted that the success of NTX-472 demonstrates the capabilities of their technology platform, which allows for the engineering of complex molecules and the identification of the most promising drug candidates. The company plans to further develop NTX-472 as a trispecific immunotherapy, aiming to create a treatment with a differentiated therapeutic and safety profile.

In addition to NTX-472, Nutcracker Therapeutics has also developed NTX-471, another mRNA therapeutic candidate targeting CD47. Unlike NTX-472, which uses a multispecific approach, NTX-471 encodes a multivalent (octavalent) antibody to achieve high specificity for target cancer cells through avidity. Preclinical data presented at SITC 2023 showed that NTX-471 had similar cytotoxic activity to existing anti-CD47 molecules, with minimal binding to red blood cells.

Nutcracker Therapeutics continues to leverage its advanced engineering and high-precision biosynthesis capabilities to develop its RNA platform, encompassing the design, delivery, and manufacturing of RNA medicines. Their technology platform boasts significant advantages in speed and scalability, potentially reducing costs and cycle times for RNA therapeutic development. Nutcracker Therapeutics' efforts are supported by clinical investigators at leading institutions, and the company is committed to advancing multiple therapeutic programs with the potential to revolutionize RNA therapy.