Public Funding for Apoha Limited

For 50 years, the UK has led the world in developing monoclonal antibodies. Today, there are over 100 monoclonal antibodies approved by the US Food and Drug Administration, and the global monoclonal antibody therapeutics market is valued at USD279.8bn (Dimension Market Research). However, efforts to develop novel therapeutics remain stymied by the persistently high failure rates, particularly at clinical stages of development, when approximately 90% of drug candidates fail. Regarding biologics, poor developability is estimated to account for one third of clinical-stage failures, costing approximately USD450m per biologic developed. Through examination of the clinical-stage antibody landscape, researchers have established the key biophysical properties that define developability (Jain et al., 2017), but screening of biophysical properties remains a formidable challenge, particularly with limited material availability. At the same time, BioTech and Pharma researchers are increasingly focused on the development of next-generation antibodies, which leverage multispecificity (e.g., bispecifics) and drug conjugation (e.g., antibody-drug conjugates) to address the therapeutic shortcomings of first-generation antibodies and improve patient outcomes. These novel antibody formats are increasingly complex and can even be entirely synthetic (e.g., engineered nanobodies), further exacerbating the developability challenge and risking even higher failure rates during clinical-stage development. Founded in 2021 by Dr Shamit Shrivastava (experimental physicist and inventor of Apoha's Liquid Brain; previously postdoctoral researcher at the University of Oxford) and Anshika Srivastava (skilled in operating and scaling businesses; previously Executive Director/Vice President, Goldman Sachs), Apoha is a seed-stage start-up based in London. Our mission is to empower scientists to design materials with new functional properties inspired by the physics of brain matter. With Innovate UK funding, we will deploy our neuromorphic sensor and computer, the Liquid Brain, to revolutionise analysis of antibody-target binding and developability, reducing development time, costs, and likelihood of clinical-stage failures, ultimately improving treatment accessibility, affordability, and health outcomes.

Lipid nanoparticles (LNPs) are sub-micron-scale spherical vesicles made of ionisable lipids. They are used to safely and effectively deliver drugs including nucleic acids such as messenger RNA (mRNA) to target cells, most prominently being deployed in Pfizer-BioNTech and Moderna's mRNA-based COVID-19 vaccines. Although receiving increasing attention, LNPs are complex to design, since they are typically composed of at least four lipid components: (i) ionisable cationic lipids (to ensure effective cell penetration and cargo release in the cytoplasm); (ii) helper lipids (to promote cell binding); (iii) cholesterol (to pack out the lipids); and, (iv) a polyethylene glycol (PEG)-lipid conjugate (to improve stability). This results in a large combinatorial space, since the individual components and the relative ratios of each must be optimised for each new therapeutic application and administration route. High-throughput assembly and in vitro screening technologies for LNPs permit traversing of this combinatorial space, cost-effectively manufacturing and analysing thousands of novel LNPs. Yet, because of time and cost constraints, only a limited number of LNPs (often, only 5-10) can be taken forward to preclinical in vivo studies. These LNPs are selected based on the results of cell-based in vitro assays. However, studies have shown that there is no correlation between in vitro and in vivo results. In other words, the in vitro models do not accurately represent in vivo behaviour. This results in high failure rates for novel LNPs at preclinical in vivo stage, increasing development costs and reducing R&D efficiency for BioTech/Pharma. Founded in 2021 by Dr Shamit Shrivastava (experimental physicist and inventor of Apoha's core platform technology; previously postdoctoral researcher at the University of Oxford) and Anshika Srivastava (skilled in operating and scaling businesses; previously Executive Director/Vice President, Goldman Sachs), Apoha is a seed-stage start-up based in London, UK. Our mission is to empower scientists to design materials with new functional properties inspired by the physics of brain matter. Founded in 2009 by PD Dr Carsten Rudolph (lead inventor of Ethris' core mRNA platform technology) and Professor Christian Plank (biochemist with expertise in targeted drug delivery), Ethris is a clinical-stage BioTech based in Munich, Germany. Ethris' mission is to redefine mRNA medicines through best-in-industry delivery, stability, and nebulization technology. Here, Apoha and Ethris will leverage the unique complementary skills and expertise of both partners to address the in vitro/in vivo predictability challenge of LNPs, reducing development costs and increasing BioTech/Pharma R&D efficiency.

Synthetic biology is poised to revolutionise future food systems, increasing sustainability, affordability, and quality for consumers, while improving resource efficiency and global food security. But, today, synthetic biology start-ups as well as FoodTech and Fast-Moving Consumer Goods innovators looking to integrate synthetic biology ingredients into novel food and beverage product formulations face three key challenges: 1. Achieving taste and texture parity with traditional food products. 2. Achieving price parity with traditional food products. 3. De-risking supply chain vulnerabilities (e.g., single-source ingredients suppliers) and scaling up synthetic biology food and beverage product manufacture to meet consumer demand. These three key challenges together create a screening and product optimisation bottleneck limited by the lack of rapid, cost-effective analytical instrumentation technologies that can analyse and model key biophysical properties of complex mixtures. Apoha is a stealth-stage start-up (UK SME), founded in 2021 by Dr Shamit Shrivastava (inventor of Apoha's core cross-cutting platform technology; ex-postdoctoral researcher, University of Oxford) and Anshika Srivastava (ex-Executive Director/Vice President, Goldman Sachs). Our mission is to prepare the world for the future where demand for new materials and computational power will soon far exceed current capabilities and capacity. We are developing a "liquid brain", a neuromorphic fluid-based technology that mimics neuron-like activity when it is exposed to a chemical. The fundamental science behind our innovation was highlighted by Scientific American in 2018 as a "Revolution in Science that could change everything". With Innovate UK support through the Engineering Biology Collaborative Research and Development Round 1 call, we will apply our emerging "liquid brain" platform technology to screening and optimisation of synthetic biology food products, unlocking multiple synthetic biology use cases including similarity analysis (e.g., comparing the taste and texture of synthetic biology food products to traditional and plant-based food products), new product development (e.g., integrating synthetic biology ingredients in place of traditional or plant-based ingredients), scale up re-optimisation (e.g., product reformulation to reduce costs by incorporating more cost-effective raw materials), quality assurance/quality control checks (e.g., analysing ingredients from different suppliers and/or from the same supplier over time), and product optimisation (e.g., to improve quality, nutrition, and/or functional properties). Our innovation aligns with the scope of this funding call, to develop tools and technologies that support synthetic biology. We are focused primarily on the National Engineering Biology Programme (NEBP) theme: food systems, with a secondary focus on cross-cutting technology and service development (e.g., extending our technology to applications of synthetic biology in biomedicine).

Drug development costs are rising and pharmaceutical R&D efficiency is falling, increasing costs for BioTech and Pharma companies, healthcare providers, and reducing affordability and accessibility for patients worldwide. 90% of drug candidates fail during clinical-stage development. Poor developability accounts for one third of clinical-stage failures of biologics, costing approximately USD450M per drug developed. High-throughput screening technologies deployed in the critical hit-to-lead phase of drug discovery are used to evaluate thousands of potential drugs against the drug target. Yet, comprehensive assessment of key biophysical properties associated with drug developability remains severely restricted by resource and time constraints, including limited material availability, particularly for biologics. Apoha is a stealth-stage start-up (UK SME), founded in 2021 by Dr Shamit Shrivastava (inventor of Apoha's core platform technology; ex-postdoctoral researcher, University of Oxford) and Anshika Srivastava (ex-Executive Director/Vice President, Goldman Sachs). Our mission is to create a new paradigm for sensing and computing that is powerful and sustainable at scale, inspired by the physics of brain matter. We are developing a "liquid brain", a neuromorphic fluid-based technology that mimics neuron-like activity when it is exposed to a chemical. The fundamental science behind our innovation was highlighted by Scientific American in 2018 as a "Revolution in Science that could change everything". With Innovate UK support, we will apply our "liquid brain" platform technology to the challenge of poor antibody developability, by developing a neuromorphic sensing and computing platform for high-throughput screening of underlying biophysical properties. We will combine our proprietary and patented hardware with cutting-edge neuromorphic algorithms trained to rank antibodies based on their developability potential. Our innovation directly addresses a key barrier to global transformative research highlighted in the UK Innovation Strategy 2021, that of declining pharmaceutical R&D efficiency and the rising cost of drug development.

High-performance liquid chromatography (HPLC) is the most widely used analytical technique in pharmaceutical analysis, with applications spanning from detection of active pharmaceutical ingredients in drug formulations and biological fluids to quality control and assurance; for example, monitoring pharmaceutical impurities and degradation products (Siddiqui, AlOthman, and Rahman, 2017). In HPLC, a sample dissolved in a solvent is injected into a column. This sample is separated into its individual components based on the different rates at which these components travel through the column. This separation relies on differences in column retention resulting from varying polarity, electrical charge, or molecular size. The separated components are detected as they elute from the HPLC column. Pharmaceutical and biotechnology companies are actively searching for a quantitative universal liquid chromatography detector for pharmaceutically relevant molecules. The Enabling Technologies Consortium (a forum for member pharmaceutical and biotechnologies companies including AstraZeneca, GlaxoSmithKline, and Pfizer) issued a request for proposals in October 2021\. Most HPLC detectors rely on UV/vis spectroscopy to detect and identify analytes in the sample, passing ultraviolet and visible light through the sample and measuring the amount of light that is absorbed. However, UV/vis spectroscopy can only be used with analytes that absorb ultraviolet or visible light, while quantitative detection relies on knowing the absorption coefficient of each analyte and is affected by solvent absorbance. Refractive index detection, while universally responsive, suffers from poor sensitivity and cannot be used with gradient chromatography, since changing solvent composition alters refractive index. Gradient chromatography is used for pharmaceutical analysis because of its higher selectivity, sensitivity, and speed compared to isocratic elution. More sophisticated techniques e.g., Evaporative Light Scattering Detection (ELDS), Charged Aerosol Detection (CAD), and Mass Spectrometry (MS) are unsuitable for semi-volatile analytes and provide poor response linearity. Apoha is developing the world's first universal HPLC detector for pharmaceutical applications. Our proprietary and patented emerging sensing technology (developed by cofounder and experimental physicist Dr Shamit Shrivastava) provides universal detection by monitoring properties that are unique to any analyte (including viscosity, electrostatic interaction, and surface tension). With Innovate UK support, we will develop our sensor technology from laboratory validation stage to prototype system demonstration with a top 5 HPLC market player. This will position us ready to raise follow-on private finance for rapid post-project commercialisation, establishing our technology in the pharmaceutical industry. Addressing declining pharmaceutical R&D efficiency and ultimately lowering the cost of drug development and enhancing pharmaceutical affordability.