NalaGenetics Moves Pharmacogenomics from the Bench to the Clinic using qPCR: An Interview with Astrid Irwanto, Co-Founder and COO

Astrid Irwanto is the co-founder and COO of NalaGenetics, a company taking a novel, personalized approach to understanding genetic susceptibility to drug reactions in Southeast Asian populations. Astrid obtained a PhD in human genetics and then explored aspects of many complex human genetic diseases in her post-doctoral studies, specifically how genetic variations relate to disease risks. Her PhD and postdoctoral work, along with personal experiences, now fuel her pursuits at NalaGenetics. Bio-Rad’s Candice Cox recently met with Astrid to ask about the history of NalaGenetics within the focus of pharmacogenomics and why she decided to translate her academic research to a molecular diagnostics company using techniques such as qPCR on the CFX Opus 96 Real-Time PCR System, among others.

Candice: Could you speak about how NalaGenetics came to be and how it proposes to impact human health in Southeast Asia?

Astrid Irwanto, PhD, is the co-founder and COO of NalaGenetics.

Astrid: During my doctorate and post-doctoral research, we published in the New England Journal of Medicine on biomarkers detecting dapsone hypersensitivity syndrome related to the treatment of leprosy, a prevalent disease in Indonesia. This syndrome is more common in Indonesia due to an HLA variant in Asian populations, commonly found in East Indonesians and Melanesian ancestral groups. We developed a low-cost qPCR assay, now used in East Indonesia, screening for this variant before dapsone treatment. It remains affordable, at $5 per test, and accessible, benefiting leprosy patients in the region. Before drug administration, leprosy patients receive a Novartis strip pack from the WHO to test for the HLA variant HLA-B*13:01; if positive, they avoid dapsone but can take other antibiotics. Nala continues to provide this test at a reduced cost.

But then we had other projects we wanted to pursue, owing to my own personal story and Levana’s personal story. My father is tetraplegic, paralyzed from the chest down, due to the administration of two anticoagulants 20 years ago for a chest pain that was thought to be a cardiovascular issue.

Candice: What side effect did the anticoagulant cause?

Astrid: An adverse reaction to the anticoagulant caused bleeding in his gums and the C3 region of his spine that was unfortunately not identified, and it led to paralysis within about 12 hours. Because about 30% of these reactions are genetically linked, actions can be taken to specifically address the problem of ADRs in countries with large Asian populations. We realized that commercial kits lack detection of a crucial mutation, *36, in the CYP2D6 gene, affecting 20–30% of Asians, notably those of Chinese descent. Nala PGx Core^® aims for inclusivity by incorporating prevalent biomarkers in Asian countries, making pharmacogenomic tests both relevant and affordable. Our vision is to make this technology as accessible as possible.

Candice: With that introduction, it’s clear that your company’s mission to improve the lives of many local groups in Asian countries came from a very personal perspective. How do you accomplish the goal of understanding population variation in Southeast Asia?

Astrid: We still do a lot of research to make sure we always refer to the local population reference if available; we’re trying to kickstart our government to do more of this work. For example, last week we signed an agreement with the Government of Indonesia to begin their first human genome project.

In Indonesia, we already see population diversity between those in Papua versus Java and Sumatra, even though geographically they aren’t far from each other. These differences in ethnicity can impact whether we have the right biomarker for dapsone hypersensitivity syndrome. For example, in the Javanese population, it’s almost zero. This information aids in better prediction of disease risk; now we’re focused on preventative medicine, which can be a challenge to emphasize compared to the concept of treatment.  

Candice: Your recent application note with us discusses how you validated your Nala PGx Core^® assay on Bio-Rad’s new CFX Opus [Real-Time PCR] System (Mahendra et al. 2023). So, when you came across the CFX Opus, why did you choose to use this real-time thermal cycler to validate the compatibility of your pharmacogenomics assay?

Astrid: Initially, familiarity with your reagents led us to ensure compatibility with the CFX96, a ubiquitous and affordable option in this region. The prevalence of your real-time PCR systems among our clients reinforced our choice. When the CFX Opus was launched two years ago, with the intent to replace the CFX Touch, we decided to validate our assays on this newer platform. Supporting clients transitioning from Bio-Rad CFX96 to CFX Opus 96 further motivated our decision, aligning with our goal of accessibility and affordability in diagnostics. In diagnostics, it’s a question of cost per test, right? The CFX Opus, with five-channel detection, also fits our needs for our Nala PGx Core^® kit requiring three detection channels. A particular variant of the CYP2D6 gene has three different types of nucleotides in the population; whether you carry a T or an A in this position determines the risk for decreased or a loss of enzyme function, which will impact drug recommendations.

Candice: Is Nala promoting preemptive testing in hospitals so that clinicians know patients’ genetic risk of an ADR (adverse drug reaction) before their hospital visit? Why is preemptive testing safer for patients than testing just at the time of a new prescription?

Astrid: Pharmacogenomics is most beneficial when used at the right time. You want physicians to make the right recommendations for products and doses. Testing someone’s genetics three days after a heart attack isn’t practical. The issue today is that this information isn’t readily available, which can lead to trial and error if a patient needs immediate medication. Having this information available in advance while a patient is in a healthy state can save time and enhance medical checkups. Our test can also save costs for insurers by reducing hospitalization for adverse reactions and the trial and error of different drugs.

Candice: What’s the advantage of a clinical customer using the Nala PGx Core^® kit to determine the genetic risk of ADRs compared to running a large NGS screen?

Astrid: Nala PGx Core^® focuses on the most impactful genes related to pharmacogenomics, making it cost-effective and efficient for clinical customers. You don’t need all the world’s genes for a pharmacogenomics test. You can target a smaller subset with the most significant impact on your population; it fits well into qPCR settings. It allows for quick results with fewer samples and is cost-effective compared to large NGS screens. As pharmacogenomics gains acceptance and becomes a national screening program, NalaGenetics is ready to scale up with more high-throughput platforms.

But we do use other molecular techniques besides qPCR in our product development. Besides qPCR, we can analyze pharmacogenomics results from microarray, short-read NGS, and are moving towards long-read NGS technology to support a wider range of platforms. Each technology has its own strengths and limitations. For example, qPCR excels in cost-effectiveness and fast turnaround, making it suitable for preemptive testing. While NGS offers more comprehensive data, it’s not as cost-effective. To promote pharmacogenomics, we need to change the mindset of the medical community. Education and outreach efforts are essential to drive the adoption of these technologies.

Candice: Thank you for sharing this great example of a successful collaboration using the Nala PGx Core^® on Bio-Rad’s CFX Opus System, showcasing the positive impact of the pilot study approach and highlighting the significance of preemptive testing for these individuals.

Your journey from academic researcher to creator of NalaGenetics shows your commitment to revolutionizing healthcare in Southeast Asia. We hope that NalaGenetics, under your leadership as the Co-Founder and COO, can achieve its mission to provide affordable and accessible genetic testing solutions and shift the medical community’s mindset about the ability to enhance patient outcomes.

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