How Programmable Biology Could Reshape Biologic Drug Development

A new collaboration between Constructive Bio and RxCelerate, announced on Nov. 19, 2025, aims to test whether an emerging class of programmable biology technologies can reshape how biologic therapeutics are conceived and developed. The two Cambridge, UK-based companies have entered a partnership to generate novel biologic candidates for such conditions as liver fibrosis and other cardiometabolic diseases—areas where drug developers continue to face significant scientific and clinical challenges (1).

The partnership centers around Constructive Bio’s programmable biology platform, which uses synthetic genomics and engineered translation to enable incorporation of non-canonical amino acids into peptides, proteins, and biologic therapies (1,2). These chemistries offer broader design options than the standard 20 amino acids, creating the potential to engineer molecules with properties that are not readily achieved through conventional protein design (2). For biopharmaceutical developers, the ability to access new chemical functionalities could influence therapeutic durability, specificity, and manufacturability (3).

Under the agreement, RxCelerate will apply its drug discovery and development capabilities—including design, engineering, and biological assessment—to evaluate how programmable biology can be integrated into early-stage therapeutic pipelines. By combining these approaches, both organizations intend to demonstrate how synthetic and engineered systems might expand the feasibility of biologics designed for diseases with limited treatment options.

“This partnership exemplifies how combining complementary strengths can accelerate innovation,” said Jill Reckless, PhD, CEO, RxCelerate, in a company press release (1). “Together, we aim to unlock new possibilities for next-generation therapeutics, demonstrating the full potential of Constructive Bio’s platform to create differentiated biologics that deliver meaningful benefits for patients."

What advantages could non-canonical amino acids bring to therapeutic development?

Constructive Bio’s programmable biology platform enables researchers to rewrite genetic sequences and reprogram protein translation, allowing cells to incorporate non-canonical amino acids into proteins at multiple positions (1). These expanded chemistries may allow developers to design biologics with greater structural precision, tailored pharmacokinetics, or enhanced stability (4). Such attributes could be increasingly important as the biopharmaceutical sector moves toward more targeted and modular approaches to treating complex diseases (5).

“This collaboration demonstrates how rewriting life’s code can redefine what is possible in drug discovery—enabling entirely new classes of biologics for the world’s most challenging diseases with powerful new-to-nature chemistries,” said Ola Wlodek, PhD, CEO, Constructive Bio, in the release, emphasizing the significance of this technological shift (1).

Although programmable biology remains an emerging field, the partnership suggests growing industry confidence in expanding beyond traditional protein engineering frameworks (6) (see Figure). For companies operating in areas such as antibodies, peptides, or engineered proteins, access to more diverse chemical building blocks could influence competitive differentiation and pipeline strategy (7).

How might integrated discovery capabilities accelerate next-gen biologics?

As part of the collaboration, RxCelerate will use its in-house discovery capabilities, including computational design, bioengineering workflows, and integrated biological evaluation. “This collaboration brings together RxCelerate’s full suite of in-house capabilities, from in-silico design and bioengineering to complex biology,” said Jon Heal, PhD, executive vice-president, ProsaRx, RxCelerate, in the press release (1). “Constructive Bio’s…programmable biology technology opens new design space for biologics, and together we’re building a program that could deliver truly novel therapeutics for diseases where current treatments fall short.”

For the broader biopharmaceutical industry, this partnership highlights how synthetic genomics and engineered translation may begin to move from research settings into therapeutic development programs (1). If successful, this work could offer a blueprint for incorporating programmable biology into drug pipelines, potentially influencing how future biologics are conceptualized, engineered, and manufactured (1).

References

1. RxCelerate. RxCelerate and Constructive Bio Announce Partnership to Advance Next Generation Therapeutics. Press Release. Nov. 19, 2025
2. Yan, X.; Liu, X.; Zhao, C.; et al. Applications of Synthetic Biology In Medical And Pharmaceutical Fields. Signal Transduction Targeted Ther. 2023, 8, 199. DOI: 10.1038/s41392-023-01440-5
3. Kesik-Brodacka, M. Progress in Biopharmaceutical Development. Biotechnol. Appl. Biochem. 2018, 65 (3), 306–322. DOI: 10.1002/bab.1617
4. Kortemme, T. De Novo Protein Design—From New Structures to Programmable Functions. Cell. 2024, 187 (3), 526–544. DOI: 10.1016/j.cell.2023.12.028
5. Badria, F. A.; De Filippis, B.; El-Magd, M. A.; et al. Editorial: Multi-Target Drug Discovery and Design for Complex Health Disorders. Front. Pharmacol. 2025, 16. DOI: 10.3389/fphar.2025.1633600
6. Shen, D.; Wang, X.; Gao, Y.; et al. An Industrial Automated Laboratory for Programmable Protein Evolution. Nat. Chem. Eng. 2025. DOI: 10.1038/s44286-025-00303-w
7. Ranbhor, R.; Venkatesan, R.; Redkar, A. S.; Ramakrishnan, V. Computational Protein Design: Advancing Biotechnology Through In Silico Engineering. Prog. Biophys. Mol. Biol. 2025, 197, 75–83. DOI: 10.1016/j.pbiomolbio.2025.07.003