Nintx
Decoding The Brazilian Biodiversity Into Multi-Target Therapies

The relentless pursuit of new and improved therapies for a host of diseases is an ever-present endeavor. While great strides have been made in discovering new treatments for various complex ailments, certain chronic multifactorial disorders, caused by a combination of genetic (biological targets) and environmental factors (nutrition, lifestyle, stress, microbiome), continue to evade. Prime among them are inflammatory diseases of the gastrointestinal (GI) tract, autoimmune disorders, cardiometabolic afflictions, cancer, and neurodegenerative disorders.

Established by eminent scientists Dr. Miller Freitas and Dr. Cristiano Guimarães and healthcare business and strategy veteran Mr. Stephani Saverio, Next Innovative Therapeutics (Nintx) offers a fresh look on the search for potent therapies to treat these multifactorial diseases.

Nintx is breaking new ground in the discovery of novel therapeutics. The biotech startup uses an in-depth understanding of the inter-relationships between various species of plants, microbes, and humans to devise innovative, revolutionary multi-target therapies that have the ability to combat diseases with varied causal factors.

Located in Brazil, home to the Amazon rainforest and a treasure trove of incredible biodiversity, Nintx seeks to unlock the immense therapeutic potential in the Brazilian flora. Nintx stands apart with its concept of using plant-based natural products (NPs) as a base to modulate concomitantly human biological targets and microbiome—groups of microorganisms present in the human body—for successful disease outcomes. The human microbiome is involved in crucial physiological processes and an imbalance between symbiotic and pathogenic microbes, favoring the latter, called ‘state of dysbiosis,’ can be a trigger for several diseases.

“From the natural products derived from Brazil’s biodiversity, we generate next-generation multi-target therapies that can simultaneously modulate biological targets in the human genome and the gut microbiome to treat multifactorial diseases,” says Dr. Freitas, co-founder, and CEO of Nintx.

A New Direction with New Technologies

To develop innovative, effective therapies, Nintx takes into consideration (i) that natural compounds made by plants and microbes have the ability to modulate biological targets in the human genome, as humans share genes with all living organisms, and (ii) the evolutionary link between microbes and plants that exists for millions of years. This link has led to the generation of NPs or metabolites that serve biological needs within or between such species. Not surprisingly, recent scientific data from the American Gut Project reveals that NPs, especially those derived from plants, can profoundly impact the human microbiome, which is populated since our birth by microbes that live among us.

In line with these findings, Nintx leverages the latest advancements in omics (metagenomics, metabolomics, and proteomics), analytical, and data analytics technologies to promote a renaissance of natural products as a drug discovery platform. To that end, Nintx employs advanced extraction, isolation, and structure elucidation techniques, high-through put screening, high resolution X-ray protein crystallography, in vivo disease models, revolutionary proprietary technologies to simulate the human microbiome, next generation DNA sequencing, and cutting-edge data analytics algorithms in order to develop multi-target therapies.

Enabling Nintx to develop therapies by projecting the effect of different NPs on humans are the startup’s proprietary technologies, GAIApath^® and xGIbiomics^®.

The former is a data analytics infrastructure that maps and selects medicinal plants with robust scientific evidence pointing to the simultaneous potential to modulate biological targets and the microbiome. With so many possibilities to choose from Brazil’s biodiversity, Nintx built a knowledge-graph solution in order to make the selection systematic and data-driven as opposed to serendipitous and arbitrary, increasing the probability of success of the selected discovery projects and reducing attrition in R&D. The xGIbiomics® technology closely emulates the human GI tract and microbiome. This in vitro system helps researchers test the NPs impact on the gut microbiome without requiring animal models or human subjects.

The xGIbiomics^® technology has five bioreactors in sequence simulating the stomach, the small intestine, and three portions of the colon (ascending, transverse, and descending). The pH, volume, transit time, oxygen level, and temperature are controlled in the different bioreactors. Digestive enzymes and bile are added to the simulated stomach and small intestinal compartments, where applicable, while inoculation with fecal microbiota from human donors (healthy volunteers or patients) only takes place in the bioreactors simulating the colon.

The simulation replicates the actual environment of a typical human GI digestive system. The Nintx team inoculates the system with the microbiome from a human subject and introduces NPs that have the potential to deeply modulate it, not only changing a state of dysbiosis to eubiosis (equilibrium) and increasing diversity of species in the gut, but also tuning specific microbes strongly associated with diseases. A diverse microbiota is a major factor in the better management of multifactorial diseases and promoting human health. This is where the Brazilian biodiversity comes at play with its diverse flora brimming with medicinal properties and incredible prebiotic potential.

“The advances in analytical, omics, and screening technologies, which can now be augmented by data science and analytics methodologies, are crucial to decode the molecular crosstalk between the different species. This can boost research on microbiome derived therapies and reboot natural products-based drug discovery. Natural products will continue to inspire novel discoveries in chemistry, biology, and medicine for many generations”, says Dr. Guimarães, co-founder, and Chief Scientific Officer at Nintx.

Setting the Stage for Therapies of the Future

Brazil has an unparalleled biological diversity. The potential for generating value from biodiversity is enormous but remains largely untapped. It is necessary to develop economic alternatives that state the obvious; that the different biomes are much more valuable standing than devastated. Nintx is driven by its founders’ dedication to bringing a proactive, first-of-its-kind approach to drug development that is on the verge of transforming the Brazilian biodiversity into a therapy powerhouse based on this incredible biological richness.

To build its business plan, Nintx devoted a considerable amount of time prioritizing global unmet medical needs in the Gastroenterology, Cardiometabolic, Immunology, Neuroscience, and Infectious Disease Therapeutic Areas (TAs), with the help of world-renowned consultants.

Due to the involvement of the human microbiome in many pathologies of such TAs, the unmet medical needs therein would benefit the most of Nintx’s multi-target therapy concept, i.e., the simultaneous modulation of biological targets and the microbiome, leading to truly disruptive therapeutic interventions.

After carefully building the business plan and prioritizing the TAs, Nintx geared up to find strategic partnerships that would bring both technical expertise and direct investments on Nintx’s projects, technologies, and infrastructure. The company has partnered with the Center for Research in Energy and Materials (CNPEM) and the Center for Innovation and Preclinical Studies (CIEnP), two of the best-regarded research institutes in Brazil, and Adeste, a prominent Brazilian company in the food, human health, and animal nutrition sectors. Five out of eight R&D projects in Nintx’s pipeline are partnered with CNPEM, CIEnP, and Adeste. From a technology standpoint, Nintx partnered with the Centroflora Group, a world class producer of sustainable botanical extracts, essential oils, and isolated natural products for the pharmaceutical industry, to build a state-of-the-art research lab to house Nintx’s xGIbiomics® technology.

Innovation with Purpose

Brazil, with its rich biodiversity, has a privileged position to assume a leading role on a new regenerative economy, with the potential to inspire transformations that, through research, science, and technological innovation, benefit not only the country, but also the rest of the world. Nintx is based on an equation that balances high technology, respect for the environment, and economic viability.

As Nintx ramped up the activities after its foundation, as demonstrated by the startup’s very busy year since its foundation at the beginning of 2021, the next step was to capture a venture capital (VC) investment that would not only bring financial resources, but was also aligned with the startup’s vision, values, and purpose. Nintx has recently secured a US $3 million seed investment. The seed round, led by deep tech VC firm Pitanga, also had the participation of Mr. Guilherme Leal (Natura & Co.) and Mr. Peter Andersen (Centroflora), entrepreneurs who practice ESG (environmental, social, and governance) guiding principles in their businesses.

Mr. Saverio, co-founder and non-executive board member at Nintx, affirms, “The world is experiencing a decentralized pharma R&D modus operandi in a highly collaborative network and digital era, allowing deep tech startups to have great notoriety and impact. There is also availability of venture capital worldwide for investments in high-risk, high-impact projects, especially in ESG projects, but not in Brazil. Pitanga is one of the few exceptions and Nintx should be extremely proud to have been selected by them and by true Brazilian giants, such as Mr. Guilherme Leal and Mr. Peter Andersen. Nintx will be a force to be reckoned with”.

Going beyond generic drugs, Nintx is pushing the boundaries of innovation in the Latin American pharma sector with its unique multi-target concept and drug discovery approach. Nintx is all set to bring the next-generation therapies poised to transform disease treatment on a global scale with the rich Brazilian biodiversity as its launch pad, promising a revolution to the global therapeutics market.