Delivering on the Promise of New Modalities: An Interview with Sue Dillon, CEO of Aro Biotherapeutics

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New modalities offer unprecedented therapeutic potential for patients, yet they also pose unique challenges. As part of WuXi AppTec’s ongoing efforts to collaboratively foster new thinking and actionable approaches in advancing breakthroughs for patients, we have launched a new interview series in 2022 – “Delivering on the Promise of New Modalities” – so leading voices of R&D can share how their approaches are addressing the barriers standing in the way of breakthroughs. Our first episode of this interview series features Sue Dillon, an industry veteran and co-founder & CEO of Aro Biotherapeutics based in Philadelphia. Aros proprietary Centyrin technology platform enables precise receptor-mediated delivery of RNA drugs to address intracellular gene targets. In Jan 2021, Aro announced $88 million Series A financing to advance development of Centyrin-Targeted genetic medicines to clinical development.

Congratulations Sue on Aro’s series A. What gaps is Aro trying to address in the field?

Sue: We are focused on developing tissue – targeted genetic medicines for patients with rare genetic muscle diseases and immune diseases with high unmet medical need. Our approach achieves selective and efficient targeting of RNA medicines, such as small interfering RNA and antisense oligonucleotides, to specific tissues thus enabling first-in-class medicines that precisely modify disease related genes. As a drug class, oligonucleotides have demonstrated dramatic clinical proof of concept for modulating disease related genes in the liver, or when locally delivered to the CNS or to the eye directly. Although this approach offers the possibility of addressing previously “undruggable” disease targets, the gap facing the field has been lack of efficient targeting and delivery of this exciting class of drugs to the many extra – hepatic tissues that cannot be addressed with local administration. Our initial work is focused on targeting siRNA drugs to skeletal muscle, heart, immune cells, and tumors.

Tell us a bit more about Aro’s Centryn platform and how is it different from others out there?

Sue: We are pioneering a new class of drugs called Centyrin – siRNA conjugates. Centyrins, Aro’s proprietary antigen-binding platform, are small, simple, and highly stable proteins.  Centyrins have been shown to bind target antigens with high specificity and high affinity, and Aro has identified Centyrins that bind to cell surface receptors which internalize post binding, thus carrying the Centyrin inside the cell. By chemically linking Centyrins with siRNAs or other oligonucleotides, we can target these gene modifying RNAs to particular tissues in vivo.  Centyrins have a number of unique properties – small size, low immunogenicity and relative simplicity of chemical conjugation and manufacturing among others – that makes them uniquely suited for targeted delivery of oligonucleotides. Using Centyrin oligonucleotide conjugates, we have shown robust gene modulation in target tissues with little to no effect in non-target tissues and have recently achieved disease relevant pharmacology in animal models.

Any challenges or risks that you foresee with Aro’s novel approaches?

Sue: We are pioneering a new class of drugs that is comprised of a protein component produced by recombinant technology in bacteria (Centyrin) covalently linked to a chemically synthesized oligonucleotide. There are no drugs of this type that have achieved FDA approval and as such, we are engaging with the FDA early to de-risk the preclinical and manufacturing IND enabling studies that will support our First-in-Human trial. Furthermore, given the nature of our molecules, there are complexities associated with species cross-reactivity for the oligonucleotide and Centyrin that complicates development.  We rely upon certain precedents (ADCs, oligonucleotides) that are not perfect analogues but can still provide valuable information. Additionally, we have recruited an excellent team of experienced scientists and developers and identified external consultants to create development plans for our first product candidate. Importantly, our learnings from our first programs will be deployed against future programs, which will reduce the risks associated with development of new pipeline assets.

Look forward to hearing more on Aro’s exciting developments as you advance programs to clinic. It is exciting to see now patients may have more and better treatment options as we gain more insights into new modalities and understand better how to overcome the challenges. How do you see the field will continue to evolve?

Sue: While small molecules and antibodies dominate the approval landscape of 2021, there are major shifts in R&D investment given new scientific breakthroughs. In recent years, the first siRNA medicine, cell therapy, and gene therapy have all achieved FDA approval. Just as it took several years for antibody drugs to become a mainstay in the pharmaceutical industry, we are at the very early stages of these new modalities. Across many of these new modalities, targeted delivery of genetic medicines to diseased tissues, while sparing normal tissues, is recognized as a barrier to achieving maximum efficacy and ideal safety profiles. We are very excited to potentially play a meaningful role in solving this issue, as Centyrins have the potential to achieve specific targeting to various tissues for a variety of drug payloads including oligonucleotides, and also more complex drug moieties including mRNA, gene editing technologies and cell therapies.

As new modalities continue to broaden and brighten new horizons of therapeutic intervention, do you see our industry collectively may be able to achieve 100+ new drug approvals at 50% of today’s cost?

Sue: I am optimistic about the industry’s ability to deliver 100+ approvals by 2030. The application of artificial intelligence and machine learning toward analyzing complex data sets and making associations across data will advance understanding about the root causes of disease and enable new classifications of disease and identification of new drug targets. At the same time, advances in precision medicine will improve success rates by identifying patients who are most likely to respond to a given therapeutic based on linking therapeutic MOA with the patient’s genetic profile. Additionally, accelerated clinical trials and the potential for singular (n=1) trials of highly customized therapeutics should shorten development timelines and reduce costs. Manufacturing costs and capacity of GMP approved sites for genetic and cell therapies are currently a significant challenge and must be addressed to make these medicines more cost effective and widely available.

Thank you Sue for your sharing Aro’s approaches in advancing breakthroughs for patients.

Sue: My pleasure.

 


 

Sue Dillon

Co-Founder, President & CEO, Aro Biotherapeutics

Sue Dillon, PhD, brings 30 years of experience in executive leadership roles at pharmaceutical and biotech companies to Aro Biotherapeutics. During her more than 16-year career at Johnson & Johnson, Sue led global Immunology R&D, and achieved numerous regulatory approvals for innovative antibody products for autoimmune diseases including REMICADE®, SIMPONI®, STELARA® and TREMFYA®. She also built a robust Immunology development portfolio through internal discovery and external licensing, and championed research into the emerging areas of the microbiome and immune repertoire profiling.

Multi-disciplinary teams under Sue’s leadership were twice recognized with the Prix Galien Award for PROMACTA® and STELARA®, each first-in-class medicines. Sue received her PhD in Immunology from Thomas Jefferson University in Philadelphia and completed a postdoctoral fellowship in Immunology at Duke University. She was named by FierceBiotech as one of the “Top Women in Biotech” in 2013.

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