A positive result in a cell culture dish once supported many cosmetic claims: a collagen marker increased, or an inflammatory pathway decreased. But consumers buy products for what happens on their skin. As claims become more ambitious, evidence standards are shifting. In vitro remains valuable, but relying on it as the entire proof story is increasingly outdated. Why are in vitro skin models losing credibility? Regulators and consumers are asking a harder question: “Does this model predict what happens in real human skin?” In vitro systems offer valuable biological insight, but they simplify a complex organ. Skin is an ecosystem of immune signalling, vascular influence, environmental exposure and microbes. What can in vitro never fully capture? Skin responses vary between individuals due to age, genetics, hormones, lifestyle and microbiome differences. The microbiome is especially complex, involving microbial interactions, immunity, metabolites and barrier function. Simplified models can provide valuable insights, but they cannot fully predict real-world skin responses. Where does in vitro still earn its place and where does it become a trap? In vitro remains a powerful tool in cosmetic science when used for the right questions. It is valuable for: · Screening ingredients · Supporting safety assessment · Comparing formulations The risk is turning a biological signal into a consumer promise. A fibroblast producing more collagen does not prove fewer wrinkles, and a growth assay does not prove improved microbiome health. The mistake is not using in vitro; it is asking it to prove more than it can. What does in vivo multi-omics actually look like? Multi-omics sounds complex, but the principle is simple: measure multiple biological layers together. A study may combine microbiome sequencing, metabolomics, transcriptomics and clinical measurements such as hydration, redness or barrier function. Instead of asking “did one marker change?”, we can ask: • Did the product alter microbial communities? • Did those changes influence biological pathways? • Did skin function improve? • Did consumers experience a measurable benefit? This moves cosmetic testing from isolated signals towards a systems-level understanding of skin. Will regulators ban in vitro-only substantiation? Probably not. The bigger shift is the rising expectation for evidence quality. Regulators are increasingly focused on whether evidence matches the claim. Validated in vitro methods remain appropriate for safety and mechanistic questions, but claims involving complex outcomes such as inflammation or visible ageing require evidence that reflects real-world effects. How fast should brands move? Strategically, not universally. Routine safety testing and early screening still have a place, but flagship products built on complex biological claims must move to a relevant human evidence base. In vitro is for understanding. Human studies for proving. Multi-omics for explaining. The strongest brands will not abandon laboratory models. They will use them within a fuller evidence ecosystem.

The vaginal ecosystem is not just a microbial community. It is a host-microbe system shaped by hormones, immunity, metabolites, and local chemistry. Multiomics, a combination of microbiome, metabolome, immune signals, and genomics, moves the field beyond "which bacteria are present?" to what they are doing, how the host responds, and what that means for health. What we know This approach has transformed understanding of the vaginal ecosystem, revealing complex host–microbe interactions, functional diversity, and links to BV, reproductive outcomes, and gynaecological cancers 1. The mix of small molecules in the vagina (metabolites) is one of the best ways to understand its state. Certain fats (lipids) help show levels of inflammation, while amino-acid by-products reflect which bacteria are present and the pH 2. The vaginal environment is different for everyone and changes over time. Simple “normal” vs “abnormal” labels miss important differences between people 3. Recent advances include AI-powered diagnostic models that integrate microbiome and metabolome data for improved BV detection 4. Impact and potential Vaginal multiomics opens real innovation pathways. Microbiome-compatible formulation: Designing intimate care that avoids disrupting the vaginal microbiome Prebiotic and postbiotic development: Targeting favourable metabolic environments, not simply eliminating bacteria. Longitudinal testing and claims: Shift from single timepoint testing to tracking changes over time (e.g. across cycles, treatment use), enabling more meaningful and defensible claims. Subtype-driven product design: Move beyond one-size-fits-all “intimate care” by developing products tailored to different dysbiosis or symptom subtypes identified through multiomics. Our position At Sequential, we approach the skin as an ecosystem, not a single pathway. Our focus is on generating measurable, real-world evidence of how formulations interact with both the barrier and the microbiome simultaneously. Using integrated multi-omics approaches, we can quantify changes in lipid composition, protein expression, microbial activity, and overall skin resilience over time. By testing formulations on diverse skin types and environments, using our global sample database, we generate insights that reflect real-world use rather than idealised conditions. References 1. Ottinger, S., et al. (2024). The human vaginal microbiota. Curr Opin Microbiol, 77, 102422. 2. Bokulich, N., et al. (2022). Multi-omics integration in the cervicovaginal microenvironment. PLoS Comput Biol, 18, e1009876. 3. Challa, A., et al. (2024). Multi-omics biomarkers of bacterial vaginosis. J Eur Acad Dermatol Venereol, 38, 1152–1165. 4. Saluzzo, S., et al. (2024). AI-powered multiomics in bacterial vaginosis. J Eur Acad Dermatol Venereol, 38,999 -1000.

The skin barrier is often described as a wall. In reality, it’s more like a living ecosystem. At its surface sits the skin microbiome, a complex community of bacteria, fungi, and viruses that don’t just exist on the skin, but actively help it function. Rather than being passive, the microbiome works alongside the physical, chemical, and immune layers of the barrier to maintain resilience, regulate inflammation, and protect against environmental stress. When this relationship is balanced, skin performs optimally. When it’s disrupted, both barrier function and skin health can decline. What we know The microbiome acts as a co-regulator of skin function, working alongside the barrier and immune system 1. The microbiome is a diverse, site-specific ecosystem. Oily, moist, and dry areas host distinct communities 2,3. Commensal microbes actively support barrier integrity through effects on keratinocytes and lipid balance 1, 4. Dysbiosis, through reduced diversity, is associated with conditions such as acne, atopic dermatitis, and psoriasis, often alongside barrier disruption 1, 5. Industry impact and potential For formulation, this changes the goalposts. It’s no longer enough to protect the barrier or consider the microbiome in isolation. The focus should be on supporting the system as a whole. Barrier-first design: Prioritising formulations that maintain hydration, pH, and lipid balance to create conditions in which beneficial microbes thrive. Microbiome-compatible actives: Using prebiotics, postbiotics, and fermented ingredients where evidence supports functional benefit. Precision skincare: Leveraging microbiome profiling and multi-omic data to match products to different skin states, environments, and life stages. Our position At Sequential, we approach the skin as an ecosystem, not a single pathway. Our focus is on generating measurable, real-world evidence of how formulations interact with both the barrier and the microbiome simultaneously. Using integrated multi-omics approaches, we can quantify changes in lipid composition, protein expression, microbial activity, and overall skin resilience over time. By testing formulations on diverse skin types and environments, using our global sample database, we generate insights that reflect real-world use rather than idealised conditions. References Lee, H, et al. (2022). Skin Barrier Function and the Microbiome. Int J Mol Sci, 23. Smythe, P, et al. (2023). The Skin Microbiome: Current Landscape and Future Opportunities. Int J Mol Sci, 24. Prajapati, S, et al. (2025). Microbiome and Postbiotics in Skin Health. Biomedicines, 13. Harris-Tryon, T, et al. (2022). Microbiota and Maintenance of Skin Barrier Function. Science, 376, 940–945. Scharschmidt, T, et al. (2025). Skin Microbiome and Dermatologic Disorders. J Clin Invest, 135.

The Future of Next-Generation Ingredients & Validation. A full day for senior R&D, innovation and scientific leaders across beauty, personal care and biotechnology, exploring multiomics, the skin microbiome, bioengineered actives and the evidence the market now demands. About the event Where ingredient innovation meets the evidence behind it Sequential is bringing together senior R&D, innovation and scientific leaders from across the beauty, personal care and biotechnology industries for an exclusive full-day event on the future of next-generation ingredient innovation and validation. Expect sharp, practical talks, a moderated roundtable and time to connect with peers. FORMAT: Talks · Panel · Roundtable AUDIENCE: Senior R&D & Innovation Leaders VENUE: Attenborough Room, The Mills Fabrica, London Voices From Across the Industry Lieve Declercq Proya Cosmetics Regenerative biotechnology, a biomimetic Collagen XVII platform, and the future of global R&D collaboration between China and Europe. Dr. Albert Dashi Sequential Chief Science Officer & Co-founder. Behind the science: how Sequential validates next-generation ingredient claims. John Milligan The Honey Pot Company Destigmatizing intimate health and formulating for the fast-growing women’s health category. Christina Patane Medik8 Longevity, the skin microbiome, and Medik8’s five-year innovation roadmap. Martin Pagac DSM-Firmenich 3D facial microbiome mapping and the emerging role of human milk oligosaccharides (HMOs) in skin health. Veronika Oudova S-Biomedic Building the live skin probiotic category, the founder’s journey from idea to market. Dr. Amir Jassim AI Specialist Formerly University of Cambridge & Cancer Research UK. A fast-paced look at where AI is accelerating discovery and validation. On the day Thursday 3 December, 9:00am – 4:30pm Attenborough Room, The Mills Fabrica, London. Timings may shift slightly as the programme is finalised. 9:00am Registration and coffee on arrival 10:15am Keynote - Lieve Declerca, Proya 10:45am - 1:00pm Speaker talks & coffee break 1:20pm Lunch 3:10pm Al in Ingredient Discovery - Dr. Amir Jassim 3:20pm Roundtable discussion - all speakers 4:05pm Networking 4:30pm Close

The Future of Next-Generation Ingredients & Validation. A full day for senior R&D, innovation and scientific leaders across beauty, personal care and biotechnology, exploring multiomics, the skin microbiome, bioengineered actives and the evidence the market now demands. About the event Where ingredient innovation meets the evidence behind it Sequential is bringing together senior R&D, innovation and scientific leaders from across the beauty, personal care and biotechnology industries for an exclusive full-day event on the future of next-generation ingredient innovation and validation. Expect sharp, practical talks, a moderated roundtable and time to connect with peers. FORMAT: Talks · Panel · Roundtable AUDIENCE: Senior R&D & Innovation Leaders VENUE: Attenborough Room, The Mills Fabrica, London Voices From Across the Industry Lieve Declercq Proya Cosmetics Regenerative biotechnology, a biomimetic Collagen XVII platform, and the future of global R&D collaboration between China and Europe. Dr. Albert Dashi Sequential Chief Science Officer & Co-founder. Behind the science: how Sequential validates next-generation ingredient claims. John Milligan The Honey Pot Company Destigmatizing intimate health and formulating for the fast-growing women’s health category. Christina Patane Medik8 Longevity, the skin microbiome, and Medik8’s five-year innovation roadmap. Martin Pagac DSM-Firmenich 3D facial microbiome mapping and the emerging role of human milk oligosaccharides (HMOs) in skin health. Veronika Oudova S-Biomedic Building the live skin probiotic category, the founder’s journey from idea to market. Dr. Amir Jassim AI Specialist Formerly University of Cambridge & Cancer Research UK. A fast-paced look at where AI is accelerating discovery and validation. On the day Thursday 3 December, 9:00am – 4:30pm Attenborough Room, The Mills Fabrica, London. Timings may shift slightly as the programme is finalised. 9:00am Registration and coffee on arrival 10:15am Keynote - Lieve Declerca, Proya 10:45am - 1:00pm Speaker talks & coffee break 1:20pm Lunch 3:10pm Al in Ingredient Discovery - Dr. Amir Jassim 3:20pm Roundtable discussion - all speakers 4:05pm Networking 4:30pm Close

The Future of Next-Generation Ingredients & Validation. A full day for senior R&D, innovation and scientific leaders across beauty, personal care and biotechnology, exploring multiomics, the skin microbiome, bioengineered actives and the evidence the market now demands. About the event Where ingredient innovation meets the evidence behind it Sequential is bringing together senior R&D, innovation and scientific leaders from across the beauty, personal care and biotechnology industries for an exclusive full-day event on the future of next-generation ingredient innovation and validation. Expect sharp, practical talks, a moderated roundtable and time to connect with peers. FORMAT: Talks · Panel · Roundtable AUDIENCE: Senior R&D & Innovation Leaders VENUE: Attenborough Room, The Mills Fabrica, London Voices From Across the Industry Lieve Declercq Proya Cosmetics Regenerative biotechnology, a biomimetic Collagen XVII platform, and the future of global R&D collaboration between China and Europe. Dr. Albert Dashi Sequential Chief Science Officer & Co-founder. Behind the science: how Sequential validates next-generation ingredient claims. John Milligan The Honey Pot Company Destigmatizing intimate health and formulating for the fast-growing women’s health category. Christina Patane Medik8 Longevity, the skin microbiome, and Medik8’s five-year innovation roadmap. Martin Pagac DSM-Firmenich 3D facial microbiome mapping and the emerging role of human milk oligosaccharides (HMOs) in skin health. Veronika Oudova S-Biomedic Building the live skin probiotic category, the founder’s journey from idea to market. Dr. Amir Jassim AI Specialist Formerly University of Cambridge & Cancer Research UK. A fast-paced look at where AI is accelerating discovery and validation. On the day Thursday 3 December, 9:00am – 4:30pm Attenborough Room, The Mills Fabrica, London. Timings may shift slightly as the programme is finalised. 9:00am Registration and coffee on arrival 10:15am Keynote - Lieve Declerca, Proya 10:45am - 1:00pm Speaker talks & coffee break 1:20pm Lunch 3:10pm Al in Ingredient Discovery - Dr. Amir Jassim 3:20pm Roundtable discussion - all speakers 4:05pm Networking 4:30pm Close