Critical Milestone Capstones Recently Disclosed Advances in its Enzymatic Synthesis Platform

EnPlusOne Biosciences, Inc., a biotechnology company harnessing the power of enzymes to deliver better RNA at scale, revealed today that it had achieved the successful synthesis of the antisense strand of the commercially approved siRNA drug, Leqvio® (inclisiran), a treatment for hypercholesteremia (high-cholesterol). Licensed from Alnylam Pharmaceuticals, Inc. by Novartis, Leqvio® currently addresses a multi-million patient population.

The advancement of EnPlusOne’s ezRNA™ platform showcases the potential for enzymatic synthesis to address the needs of a rapidly expanding therapeutic siRNA market. This news comes as the industry faces increased demand for RNA that cannot be produced by chemical synthesis alone. Leqvio® is frequently used as a case study to illustrate the manufacturing challenges of serving large patient populations with RNA therapeutics and as a call for innovation in synthesis technologies.

Critical milestones recently achieved by EnPlusOne, some of which were disclosed in a presentation at the TIDES 2024 conference, include:

  • Synthesis of Leqvio® Antisense Strand The enzymatically-synthesized 23-nucleotide (23-nt) sequence is fully modified with 2’-F and 2’-OMe nucleotide modifications along with two leading and trailing phosphorothioate (PS) backbone modifications.
  • First known template-independent enzymatic synthesis of a fully natural siRNA length oligonucleotide (23-nt) The Company’s water-based ezRNA™ platform synthesized natural RNA without the protecting groups required for other approaches.
  • Synthesis of therapeutically relevant blockmers (5-6-nt) The ezRNA™ platform showcased clear differentiation from templated enzymatic synthesis platforms and its ability to complement RNA ligation approaches.
  • Demonstration of >50 enabling modifications of therapeutic RNA Access to these modifications may unlock a suite of opportunities for the design and discovery of novel RNA therapeutics.

“We are very pleased to have achieved these groundbreaking milestones in building out our ezRNA™ synthesis platform,” said Jonathan Rittichier, PhD, co-founder and Chief Scientific Officer of EnPlusOne. “Altogether, these elements move forward the promise of commercial scale enzymatic RNA synthesis, marking a critical step in our journey to meet the growing need for therapeutic RNA in the life science industry.”

EnPlusOne was launched in 2022 to commercialize its enzymatic RNA oligonucleotide synthesis technology developed in the laboratory of co-founder George Church, PhD. Seed financing was led by Northpond Ventures, with participation from Breakout Ventures, Coatue, and individual investors.

EnPlusOne’s co-founder and Chief Operating Officer Dan Ahlstedt added, “These advances demonstrate EnPlusOne’s leadership in enzymatic oligonucleotide synthesis and position us well to broaden external partnership engagements. We believe our progress over the last year highlights the importance of technical innovation in the pivotal field of enzymatic RNA synthesis, and we look forward to continued dialogue with a widening range of RNA therapeutics and manufacturing companies.”

About EnPlusOne Biosciences

EnPlusOne is enabling the future of RNA therapeutics. Its ezRNA™ platform is a revolutionary innovation that harnesses the power of enzymes to synthesize RNA and can incorporate a diverse array of natural and modified nucleotides. Their enzymatic, water-based approach promises to unlock sustainable and scalable commercial manufacturing of RNA therapeutics. For more information, please visit www.enplusonebio.com.

Mary T. Conway Conway Communications mtconway@conwaycommsir.com 617-407-8778