What do customers want? The answer is obvious yet important because the customer is the boss, and frequently, an unforgiving one. A force naturelle, the Customer gravitates toward products or services with the highest quality, supplied at the lowest possible cost, in the shortest amount of time. Accordingly, new cell and gene therapy companies emerge from stealth mode each week to solve the problems of unpredictable efficacy, extreme cost, and protracted development timelines. On the other hand, biotech newCOs often fail because it’s challenging to thread through the three-way “iron triangle” of quality, cost, and time (“QCT”)—especially when human health is at stake and quality cannot budge.

Under such severe constraints, [1] where is the future of cell and gene therapy? Perhaps it lies in companies who collaboratively approach biotechnology’s QCT dilemmas with an industrial mentality, [2] transforming the artisanal status quo into a system with interchangeable spare parts, modular process designs that employ automation, and universal manufacturing standards. This requires networking, building an ecosystem with “symbiotic” allies who can provide the most balanced solutions. In this blog, we thus highlight four exemplar new companies that might become the next “talk of the town” for all those right reasons. You might label them with the snazziest buzzword for “next-gen” (but perhaps avoid the terms “game-changing,” “paradigm-shifting,” “disruptor”). Or just read on…and simply call them “cool.” 😎

Adva Biotechnology, near Haifa, Israel, redefines what a bioreactor can be for autologous cellular therapies. It’s an understatement that many human primary cell types need far superior TLC than what big steel tanks with impellers can provide. That is partly because each new seeded population of even highly similar human cells can behave differently in its new environment, consuming and releasing metabolites according to subtle and yet dynamic influences. But how do you scale to human-sized doses as per “GMP in a box?” [3] Established in 2016, Adva addresses these costly advanced therapies with variable performance by giving human cells a good “home” to grow up in. It combines automation with advanced in-line sensing and AI to allow tight, real-time control over the cell culture during expansion and upstream bioproduction via a technology it calls Continuous Adaptive Multiparameter (CAMP®). CAMP is embedded in the ADVA X³ bioreactor system, an “all-in-one” instrument that can be part of a cGMP process suitable for applications like CAR-T, CAR-NK, TILs, exosome, and virus production.

Green Elephant Biotech of Giessen (Gießen, Hesse) spotlighted a proverbial Elephant in the Room with its founding in 2021. They noticed multi-ton mountains of plastic biowaste tossed in autoclaved bags and thankfully said this will not do. They adapted a concept that is based on the 2500+ year-old Archimedes screw pump, whose interior threads move fluids (here, culture media) through a cylinder as it spins on its axis, angled at 10^o-15^o. This mechanism facilitates extremely efficient and low volume::surface area ratio (cm³/cm²), excellent oxygenation, and favorable growth. The result? Consume 80% less plastic. And the plastic that is consumed is made via highly biocompatible and GRAS polylactic acid (PLA), from plants, produced with 90% lower carbon footprint. A variety of product formats are available for small-to-large scale uses to help investigators and the producing industry help the Earth and meet their sustainability goals.

Was Duke Ellington referring to Kolibri of Paris, France when he famously declared: “If it sounds good, it IS good”? (One wonders what sounds “musically good” to cells in culture.) Surprisingly, it appears that Kolibri (founded 2021) has cracked the code of optimized acoustic waves directed into tissue culture environments, increasing the yield of products like AAV capsids and reducing production costs. Kolibri reports “100x increase in cell density and 50x reduction in production costs…Being cell-agnostic and scalable, our process has significant potential across a range of high-value cell-based therapies – or in the cellular agriculture space more broadly.” These impressive efficiencies via sound must surely be music to your ears—and perhaps inspiring enough for your cell culture to get up and dance!

Ronawk was founded in 2019 via technology developed at the University of Kansas to improve and standardize cultured cell quality, reduce overall costs, and accelerate timelines for research breakthroughs. It’s “plane-ly” 😉 obvious that human cells in their natural state do not grow on anything resembling a 2D, plastic surface. Ronawk thus features a product system of modular, microchannelled 3D tissue-mimetic structures to replace the age-old tissue culture flask. Named “Bio-Blocks,” these facilitate “real-time visualization, efficient nutrient exchange, and compatibility with tissue processing techniques.” Bio-blocks come in at least three product formats: (i) X-blocks for ease of cell expansion and retrieval by user-timed degradation; [4, 5] (ii) surface customizable T-blocks for physiological modeling of multi-cell type tissues and organoids; and (iii), E-blocks for production of extracellular secretome products like exosomes/extracellular vesicles (EVs), conditioned media, particles, or proteins. There is a growing literature of how the Tissue-Mimetic-Bio-blocks improve key features of cells grown in high density on these porous, easily manipulatable substrates across parameters like maintenance of stemness, better wound-healing capacity, [6] and reduced senescence. In the coming months and years, watch for product expansion into cGMP-certified materials and demonstrations of Bio-blocks to employ very large scales of production within small footprints.

Like the vertices of a star, the innovative new companies of Adva Bio, Green Elephant, Kolibri, and Ronawk each shine from their own discrete domain of excellence and yet are part of a much larger unified whole. It’s not even difficult to imagine how each could interface with one another collaboratively. This is because all harness unique aspects of industrialization of advanced therapies to catalyze more favorable quality, cost and timing (QCT). Adva bridges advanced sensing and AI to standardize bioreactor outputs for cGMP autologous cell therapies. Green Elephant borrows an ancient irrigation machine and reinvents it to help cells flourish with far less waste and environmental hazard. Few would have imagined Kolibri, whose acoustic waves might even be propagatable in musical patterns—with astonishing results. Finally, Ronawk revolutionizes the geometry of practical tissue culture, literally driving cell culture into a new dimension with its modular bio-block units.

RoosterBio aims to industrialize the biomaterial supply chain and achieve scalable solutions for advanced cell therapies and their secreted exosome products. As with the others in this list and elsewhere, RoosterBio cannot and doesn’t do so alone, not as a lone wolf. We cut our teeth on many of the same kinds of problems, but in radically different ways—and sometimes divvy up the scope of ambitious new projects with collaborators and partners, [7, 8, 9, 10] progressing with agility often lacking in larger institutions. After all, patients are waiting. To you, the reader of this blog, we pose a question: What are other examples of new life sciences companies who aim to fashion a more easily threaded “needle” via an improved triangular “eye” of quality, cost, and time?   

References

1. Kim, J. H., et al., Perspectives on the cost of goods for hPSC banks for manufacture of cell therapies. NPJ Regen Med, 2022. 7(1): p. 54. 10.1038/s41536-022-00242-7
2. Rowley, J., Boychyn, M., Kelly, T. Why Cell Manufacturing Matters: How Bioprocess Innovations Have Laid the Foundation for a Cell-Based Products Revolution. BioProcess International, 2022.
3. Kadauke, S., et al., In-Hospital Manufacturing of Cellular Therapies Using Automated Systems. Clin Chem, 2023. 69(9): p. 954-960. 10.1093/clinchem/hvad102
4. Hodge, J. G., J. L. Robinson, and A. J. Mellott, Mesenchymal Stem Cell Extracellular Vesicles from Tissue-Mimetic System Enhance Epidermal Regeneration via Formation of Migratory Cell Sheets. Tissue Eng Regen Med, 2023. 20(6): p. 993-1013. 10.1007/s13770-023-00565-6
5. Hodge, J. G., J. L. Robinson, and A. J. Mellott, Tailoring the secretome composition of mesenchymal stem cells to augment specific functions of epidermal regeneration: an in vitro diabetic model. Front Med Technol, 2023. 5: p. 1194314. 10.3389/fmedt.2023.1194314
6. Hodge, J. G., et al., Tissue-mimetic culture enhances mesenchymal stem cell secretome capacity to improve regenerative activity of keratinocytes and fibroblasts in vitro. Wound Repair Regen, 2023. 31(3): p. 367-383. 10.1111/wrr.13076
7. denovoMATRIX GmbH and RoosterBio, Inc. White Paper: 3D Manufacturing of Therapeutic hMSCs with RoosterNourish™-XF & beadMATRIX. 2021.
8. ISCT22: RoosterBio, ShiftBio partner to harness the power of MSCs, exosomes. The Science Advisory Board, 2022.
9. Maryland Stem Cell Research Commission Announces Over $14 Million in Awards to Accelerate Cures. The Maryland Stem Cell Research Fund (MSCRF.org), 2023.
10. Patel, A. Accelerating the Development of a Novel Cell Therapy for COVID-19–Associated Lung Fibrosis. pharma’s almanac, 2021.