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.

In our latest interview, we’re joined by Nikole Kimes, CEO & Co-Founder of Siolta Therapeutics, a clinical-stage biotech company that was awarded an NIH grant earlier this year and has raised $35 million to date for the development of live biotherapeutic products (LBPs) for the prevention and treatment of diseases of high unmet medical need. Siolta’s proprietary Precision Symbiotics platform has allowed the company to build a robust pipeline of potential first-in-class microbiome-based medicines and diagnostics for allergic diseases, women’s health, and rare pediatric indications.

Congratulations on your recent NIH grant funding and thank you for joining us, Nikole. For drug discovery & development related to allergic diseases, what are the challenges in current therapeutic intervention, or current modality solutions?

Nikole: Current medicines are exceptionally good at alleviating the symptoms of diseases; however, most approaches fail to address the underlying causes of disease and do not provide long-term benefits, particularly when dealing with complex multifactorial diseases that dominate modern society. Traditional pharmaceuticals typically involve a single molecule that targets a well-defined pathway and results in the alleviation of a specific symptom. Although the pharmaceutical industry’s investments in this approach have been successful in many ways, it leaves a lot to be desired if our ultimate goal is to cure diseases with modalities that do not require lifelong chronic treatments or better yet to prevent diseases from happening in the first place. To address these more challenging goals, we are currently witnessing a shift towards more dynamic approaches in the world of biologics. At Siolta Therapeutics, we aim to utilize the vast repertoire of genes and functionality that the human microbiome contributes toward maintaining human health to develop a new class of biologics, called live biotherapeutic products (LBPs), that offer long-term clinical benefit in disease areas where existing modalities have failed.

What is your new modality or technological approach helping to address the challenges? How is it different from existing approaches?

Nikole: We are embracing the dynamic and complex nature of human biology to develop next-generation microbiome-based medicines capable of addressing difficult diseases driven by multiple mechanisms of action. Improving upon food-grade probiotics and donor-derived fecal microbiota for transplantation (FMT) approaches, we are developing LBPs that contain defined bacterial consortia. To do this we isolate beneficial microbes from the human microbiome (i.e., fecal, vaginal, and other sample types) and combine synergistic organisms capable of reshaping and redirecting human physiology to maintain the metabolic and immunological balance required to support human health. Our approach initially incorporates human clinical data to direct early product design and requires an in-depth understanding of each microbe’s functionality (e.g., barrier function, pathogen inhibition, and immune modulation) and their complex downstream metabolic signaling to select the ones that provide the greatest therapeutic benefit for a given patient population.

What are some critical challenges in realizing the full potential of your new modality or technologies? What are the solutions and do you anticipate any recent milestones?

Nikole: Integrating the complexity of systems biology into more traditional drug development processes presents a number of challenges, including novel regulatory considerations, complex manufacturing, and unique clinical trial approaches. To address these challenges, we had to be creative throughout the entire R&D continuum to expand the in-house expertise needed to develop this novel treatment modality. From a regulatory perspective, we continue to work with the FDA to align expectations around the unique aspects of LBP development that make traditional toxicology, pharmacokinetic, and pharmacodynamic measures irrelevant. Our internal expertise was also essential from a manufacturing perspective, allowing us to overcome the difficulties associated with large-scale manufacturing of strict anaerobic organisms. Having overcome the many challenges of this exciting emerging field, we have safely and efficiently advanced our lead program STMC-103H into Phase 2, a proof-of-concept study in the US and Australia, for the prevention of allergic diseases (atopic dermatitis, food allergy, asthma, and allergic rhinitis) in at-risk newborns.

Do you see novel technologies, AI or machine learning being used in the next couple of years?

Nikole: Absolutely, machine learning is an important tool we use to identify and predict key features of a given system, and it plays an important role in our platform by supporting diagnostic development and informing patient stratification methods. This is an area that we believe will continue to have important contributions in our design of new consortia for a wide range of indications. Progressing beyond current machine learning methods to even more advanced AI-driven drug design (e.g., deep learning) will require incredible amounts of data across various populations and longitudinal timepoints. As we strive to move towards a precision medicine model in our healthcare system, we believe that developing diagnostic tests associated with the diseases we are targeting and recognizing factors that drive patient response are essential components of this equation, and core to our strategy. This approach can be iterative and allows us to identify new consortia combinations that could improve patient responses in distinct subsets of the population in order to have the most profound therapeutic impact.

What do you think we will achieve as an industry in the next 10-15 years? What do you think are going to be some game changers in the future?

Nikole: I would like to think that we will look back and appreciate a multitude of advances, including the incorporation of precision medicine concepts to improve efficacy standards and a focus on early intervention and prevention. Going from a symptomatic relief approach to disease-modifying will likely be one of the biggest changes we will observe. In addition, targeted approaches, such as gene editing (whether human or microbial) to treat genetic disorders, cell therapies for the management and potential cure of cancer, and microbes designed to prevent diseases before they start will transform our understanding of the human health. Interestingly, as we continue to embrace more complex approaches to drug development as evidenced in the world of biologics, I also believe we will begin to see even more transformative approaches through the combination of emerging modalities. There is a lot to be excited about!

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Nikole Kimes, Ph.D.

CEO & Co-Founder, Siolta Therapeutics

Nikole E. Kimes, Ph.D., is Chief Executive Officer and co-founder of Siolta Therapeutics, a clinical-stage biotech company developing targeted live biotherapeutic products (LBPs) for the prevention and treatment of diseases of high unmet medical need. Siolta’s growing pipeline of first-in-class LBPs focuses on inflammatory conditions, women’s health, rare pediatric indications, and more. Dr. Kimes leads a talented and passionate team of researchers and clinicians with expertise in microbiology, immunology, bioinformatics, clinical operations, diagnostics, and manufacturing. An inventor of Siolta’s technology, her research in Dr. Susan Lynch’s lab at UCSF, also a co-founder of Siolta, provided the foundational translational research for the company’s formation.

In addition to her scientific and entrepreneurial pursuits at Siolta, Dr. Kimes is the chairwoman of the Microbiome Therapeutics Innovation Group (MTIG) board, an independent 501(c)(6) coalition of companies leading the research and development of FDA-approved microbiome therapeutics and microbiome-based products to address unmet medical needs, improve clinical outcomes, and reduce health care costs.

Dr. Kimes was also a member of the Springboard Health Innovation Hub: Life Sciences Track 2018 and participated in the 2017 California Life Sciences Institute’s FAST Program. She has over a decade of research experience in microbial ecology and host/microbe interactions, previously supported by a National Science Foundation (NSF) Fellowship and a postdoctoral scholar position at UCSF.