Why Prime Movers Lab Invested in Zafrens
Prime Movers Lab leads Series A for massively parallel multi-modality drug discovery platform company Zafrens.
The speed of drug discovery is limited by our ability to generate experimental data. To design a novel medicine involves tediously making and testing molecules over and over until a few hits meet a long list of essential criteria. Mining chemical data by traditional methods, a biopharma company could burn through tens of millions of dollars screening large libraries containing hundreds of thousands or even millions of molecules against a single desired target. Looking more deeply at the mechanisms or cell-to-cell interactions, secretions, and other functional assays dramatically increases the costs. Applying this conventional, brute-force approach to the interrogation of all of the thousands of putative drug targets could take a company millennia and cost more than a trillion dollars. If humans intend to solve disease, we must greatly accelerate the throughput and reduce the costs of experimentation.
Enter Zafrens, a startup pushing the boundaries of early-stage drug development. Zafrens utilizes nanofabrication to miniaturize experiments to conduct multi-modality drug discovery at single-cell resolution. The company’s innovative platform is an easy-to-use, ultra-high throughput system that enables the screening of hundreds of thousands of molecules in a reproducible manner, significantly expediting the drug development process. Prime Movers Lab led a $23M Series A investment in Zafrens to support this profoundly important scientific endeavor, spearheaded by Dr. Kandaswamy (Swamy) Vijayan. A stellar group of existing and new investors participated in the round, including BlueYard Capital, KOFA Healthcare, Global Brains, FoundersX Ventures, Alix Ventures, Possible Ventures, IASO Ventures, Hawktail, and other investors. The financing will be used to pursue applications of the company’s Z-Screen™ platform through value-added partnerships and to advance their growing internal pipeline. Below, we outline the reasoning behind our investment:
At Prime Movers Lab, “Human Augmentation” stands as a central pillar of our investment thesis. The desire to enhance or optimize human health is deeply embedded in our mission, and we invest strategically toward these aims. Zafrens embodies this mission by integrating concepts from artificial intelligence, biology, chemistry, and physics into a single platform to watch cells interact with molecules in real time, at incredible scale. They aim to leverage their platform to scale screening campaigns and democratize the drug development process.
Zafrens pulls the future forward by conducting drug discovery experiments simultaneously across hundreds of thousands of individual capture wells to perturb biology at the physical limits of detection.
As investors, we consider numerous data points during due diligence on a company. Arguably, one of the most critical considerations is whether the founder possesses the necessary attributes for success, which encompasses qualities like intellect, charisma, tenacity, and fervor. As investors, we are ourselves entrepreneurs and operators, and a “roll-up-your-sleeves” mentality is critical. Swamy not only boasts a technical background, having earned his PhD in theoretical physics from the University of Pennsylvania, but also possesses business acumen for starting, building, and scaling companies. Swamy began his career at Illumina and built two biotechnology companies, Omniome (acquired by PacBio for $800M) and Plexium (securing over $100M in Series B funding and collaborations with Amgen and AbbVie). With Zafrens, Swamy’s resolve has been redoubled, which comes through in the energy he brings to building this vision. It has been a pleasure working with a seasoned operator to rapidly prosecute such a complex organizational build, and create a strong, growing group of elite scientists, engineers, and operators around the company.
The remainder of the Zafrens team each possess deep expertise built through careers steeped in drug discovery and laboratory instrumentation platforms at prominent large and small pharmaceutical companies, research institutions, and other platform companies. Critically, the team will need to continue to bring in top discovery scientists and computational biologists, who we believe will be attracted to Zafrens’ team for the opportunity to collaborate with other great scientists generating and mining the large-scale experimental data and sharing in the potential to discover so many new medicines.
The drug discovery industry has to fail faster to succeed. Drug discovery and development is an expensive, trial-and-error process. Still, approximately 90% of drug candidates fail. We must fail faster, at a much lower cost. Developing, synthesizing, and experimentally validating novel molecules demands an extraordinary activation energy in terms of finances, effort, and time. Typically, the drug development pipeline begins with target validation, compound screening, and lead optimization. Following these stages, the drug can be tested on a model organism, such as a mouse. If proven safe and efficacious, it can then proceed to clinical testing. If not, go back several steps and start anew. These initial stages can incur costs in the millions or tens of millions and take approximately 4–5 years.
As an industry, we have to ask ourselves: What if we could compress this initial timeline from years to months, weeks, or even days at a fraction of the cost? How would you build that technology and the business around it? These questions inspired Zafrens to develop their ultra-high throughput and deep resolution platform, called Z-Screen™, capable of conducting more than a hundred thousand experiments in parallel. These experiments encompass molecule synthesis, functional screening, and multi-omic sequencing all simultaneously imaged and able to link barcoded molecular data with functional data. As a result, a single bench scientist can conduct million-scale compound screens, structure-activity relationship (SAR) campaigns, mechanism of action (MoA) studies, and lead optimization in an end-to-end assay platform.
For decades, microtiter plates with 96, 384, or up to 1536 wells have been the standard for biomedical research. Zafrens pulls the future forward by conducting drug discovery experiments simultaneously across hundreds of thousands of individual capture wells to perturb biology at the physical limits of detection. At the core of the Z-Screen™ platform is a small plastic chip, about the size and shape of a traditional microscope slide, featuring capture wells designed to deterministically load a single cell per well, enabling the isolation of up to 200,000 individual cells per chip. The chips are loaded onto the stage of a modified bright field light microscope, and interactions between each individual cell and one of hundreds of thousands of different perturbations (barcoded molecules) are observed simultaneously. The platform is highly flexible, allowing for small molecules, antibodies, RNA, or CAR-T cells to be assayed. The cells can be removed individually where desired or washed out and analyzed by in-depth multi-omic analyses. Zafrens also devised proprietary combinatorial synthesis and barcoding approaches to generate novel molecules at an ultra-high throughput rate and testing. Incredibly, their single-cell-single-well scale makes this process use up significantly fewer reagents per reaction, reducing cost by orders of magnitude. The Z-Screen platform’s flexibility and multi-modality are notable for the variety of programs the team has been able to pursue and validate internally and with partners in a short time.
The improvements in speed and cost afforded discovery scientists are further accelerated by the flexibility and the scale of high-resolution experimental data generated by the system. The rich complexity of the platform’s experimental data allows for downstream analysis at unprecedented fidelity and scale. Due to the adaptability of their platform, numerous potential applications can be addressed. Complex immunology experiments, such as T-cell receptor discovery and CAR-T optimization, can be streamlined. Cell-cell and target-receptor interactions can be investigated at a massive scale. Antibodies, bi-specifics, and multispecific discovery and optimization can be combined into a single end-to-end methodology. The platform can explore RNA-binding molecules or RNA therapeutics themselves. As such, the market (or combination of markets) they chose to pursue is substantial. The drug discovery services and drug development market is currently growing rapidly — the space is set to double over the next 5 years. Their multi-modality platform positions Zafrens to collaborate with major pharmaceutical companies across the industry while maintaining the ability to prosecute an internal pipeline of assets and validate new therapeutic approaches as they evolve.
With funding from Prime Movers Lab, Zafrens will be empowered to expand its team and scale operations. This funding will support further platform optimization, scaling in validated application areas, the discovery of new applications, and partnerships with companies at the forefront of their respective modalities. In the realm of cutting-edge science, Zafrens emerges as a trailblazer of convergent technologies taken to their physical limits for a high-value application space. Prime Movers Lab is proud to catalyze a new era of biomedical advancements, back a promising and ambitious team, and accelerate drug discovery at scale.
Special thanks to Ted Ling Hu, PhD, PML Research Fellow in Spring 2023, for co-authoring this post and supporting the screening of more than 700 companies that ultimately led to PML’s investment in Zafrens.
Prime Movers Lab invests in breakthrough scientific startups founded by Prime Movers, the inventors who transform billions of lives. We invest in seed-stage companies reinventing energy, transportation, infrastructure, manufacturing, human augmentation, and agriculture.
