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Sam Deutsch

Sam Deutsch

Chief Scientific Officer
Nutcracker Therapeutics
02 May 2024

How would you describe the promise of RNA therapies?

RNA therapies offer a transformative approach in medicine, utilizing the body‘s own mechanisms to reprogram cells and tissues towards a healthy state. The key lies in precisely engineering and delivering RNA to the right cells and tissues. RNA‘s role, often equated to the software running cells, presents a unique opportunity to harness the body‘s inherent biology towards therapeutic processes. 

Specifically, at Nutcracker Therapeutics, we are exploring ways to temporarily reprogram healthy tissues to produce therapeutic molecules. These molecules, encoded by mRNA, target disease areas such as cancer or autoimmune disorders. The transient nature of RNA reduces the risk of permanent alterations, reverting tissues back to their normal state after the therapeutic action is completed.

How does Nutcracker Therapeutics address the challenges of RNA manufacturing scale?

Contrary to common belief, the scale-up of RNA is not as problematic today, thanks in part to advancements during the COVID-19 pandemic. Moderna and Pfizer/BioNTech, for example, scaled up production to meet global demand. 

However, the challenge now shifts to producing diverse types of RNA consistently and reproducibly on a smaller scale, suitable for research or early phase clinical trials. Nutcracker Therapeutics' approach focuses on end-to-end scalability, ensuring consistency in product quality regardless of the production scale. Our technology, which includes our Nutcracker Manufacturing Unit,  emphasizes reproducibility and scale-out strategies. We utilize biochip-based microfluidics platforms, capable of producing different RNAs at various scales with minimal risk of contamination and reduced operator intervention. This setup is particularly suited for personalized medicine, where manufacturing needs to be adaptable, automated, and efficient, so that we can produce n-of-1 therapies on the same device     .

Could you elaborate on the value proposition of Nutcracker Therapeutics’ integrated platform?

Nutcracker Therapeutics' unique proposition lies in combining therapeutic development with an advanced manufacturing platform. Our biochip-based microfluidics system is pivotal for producing mRNAs at varying scales. While it may not be ideal for producing billions of doses, it excels in creating personalized medicines and can scale up for treatments intended for hundreds of thousands of patients. This integrated approach facilitates the seamless transition from small-scale research to commercial production, addressing common challenges in clinical development where processes often falter when scaled up.

Can you provide insights into your current product pipeline?

Our pipeline includes products in various stages of development, focusing on attainable goals in the coming years. One exciting aspect of mRNA therapy is its capacity to combine different mRNA molecules, each with a unique mechanism of action, within a single product. This multimodal approach is particularly effective against diseases like cancer, where attacking with multiple therapeutic angles can prevent resistance development.

Our first product candidate, NTX-250, targets cervical dysplasia a precursor to cervical cancer, and may be found useful for potentially treating other HPV-driven cancers. It combines a vaccine component against HPV, an immunomodulator to make the tumor environment more receptive to immune attacks, and a T-cell co-stimulator to establish long-term immune memory against the tumor. This multifaceted strategy exemplifies how RNA therapies can offer novel and effective treatments for complex diseases.

What components are still missing in your platform?

Our platform at Nutcracker Therapeutics consists of several components: the biochip, the hardware interface, purification processes, and the software that orchestrates everything.

The biochip acts as a reactor for RNA synthesis, integrated into a platform for loading reagents and processing RNA. Post-synthesis, RNA purification is also vital, involving precise filtration before packaging. Another crucial component is the delivery technology. We have developed our proprietary Nutshell delivery vehicle library, a nanoparticle-based system that facilitates RNA uptake by cells. Lastly, there is the design aspect, focusing on creating therapeutically effective RNA. This involves selecting suitable proteins for mRNA programming, ensuring optimal pharmacological properties, and considering manufacturability. While our current solutions are state-of-the-art, continuous innovation is essential in the rapidly evolving field of mRNA technology.

Has the interest in mRNA advancements waned post-pandemic?

The success of mRNA vaccines during the pandemic validated mRNA as a viable drug form, but it also led to an overcapacity issue in mRNA production. The biotech sector, including mRNA, has faced challenges in 2022 and 2023, affecting investment flows and market valuations. This crunch impacted companies across the board, leading to more conservative operational modes. However, the landscape is gradually changing, and companies that are prepared, like Nutcracker Therapeutics, are well-positioned to capitalize on emerging opportunities.

How important are partnerships for Nutcracker Therapeutics at its current stage, and do you plan to share your platform with other companies?

Partnerships are crucial for Nutcracker Therapeutics, as they are for most pre-public biotech companies. The funds raised are often adequate for patent and early stage asset development, but clinical progression requires significantly more investment. Partnering with companies that have expertise in later-stage clinical development is critical.

We are open to partnerships, not just for our assets, but also for sharing our end-to-end platform, which encompasses design, manufacturing, and delivery technologies. This integrated approach optimizes drug development, a challenging task if a partner only specializes in one component. Our platform's comprehensive nature makes it an attractive option for partners seeking to expedite their mRNA medicine development.