arXiv subjects

Sebastian M. Schmon

Publications and source records attributed to Sebastian M. Schmon.

9 recordsLinked to original sources

arXiv2026

Latent-Y: A Lab-Validated Autonomous Agent for De Novo Drug Design

Drug discovery relies on iterative expert workflows that are slow to parallelize and difficult to scale. Here we introduce Latent-Y, an AI agent that autonomously executes complete antibody design campaigns from text prompts, covering literature review, target analysis, epitope identification, candidate design, computational validation, and selection of lab-ready sequences. Latent-Y is integrated into the Latent Labs Platform, where it operates in the same environment as drug-discovery experts with access to bioinformatics tools, biological databases, and scientific literature. The agent can run fully autonomously end-to-end, or collaboratively, where researchers review progress, provide feedback, and direct subsequent steps. Candidate antibodies are generated using Latent-X2, our frontier generative model for drug-like antibody design. We demonstrate the agent's capability across three distinct campaign types: epitope discovery guided by therapeutic specifications, cross-species binder design, and autonomous design from a scientific publication targeting human transferrin receptor for blood-brain barrier crossing. Across nine targets, Latent-Y produced lab-confirmed nanobody binders against six, achieving a 67% target-level success rate with binding affinities reaching the single-digit nanomolar range, without human filtering or intervention. In user studies, experts working with Latent-Y completed design campaigns 56 times faster than independent expert time estimates, compressing weeks of work into hours. Because Latent-X2 is a general-purpose atomic-level model for biologics design, the same agent architecture naturally extends to macrocyclic peptide and mini-binder design campaigns, broadening autonomous discovery across therapeutic modalities. Latent-Y is available to selected partners at https://platform.latentlabs.com.

q-bio.BM↗

arXiv2025

Drug-like antibodies with low immunogenicity in human panels designed with Latent-X2

Drug discovery has long sought computational systems capable of designing drug-like molecules directly: developable and non-immunogenic from the start. Here we introduce Latent-X2, a frontier generative model that achieves this goal through zero-shot design of antibodies with strong binding affinities, drug-like properties, and, for the first time for any de novo generated antibody, confirmed low immunogenicity in human donor panels. Latent-X2 is an all-atom model conditioned on target structure, epitope specification, and optional antibody framework, jointly generating sequences and structures while modelling the bound complex. Testing only 4 to 24 designs per target in each modality, we successfully generated VHH and scFv antibodies against 9 of 18 evaluated targets, achieving a 50% target-level success rate with picomolar to nanomolar binding affinities. Designed molecules exhibit developability profiles that match or exceed those of approved antibody therapeutics, including expression yield, aggregation propensity, polyreactivity, hydrophobicity, and thermal stability, without optimization, filtering, or selection. In the first immunogenicity assessment of any AI-generated antibody, representative de novo VHH binders targeting TNFL9 exhibit both potent target engagement and low immunogenicity across T-cell proliferation and cytokine release assays. The model generalizes beyond antibodies: against K-Ras, long considered undruggable, we generated macrocyclic peptide binders competitive with trillion-scale mRNA display screens. These properties emerge directly from the model, demonstrating the therapeutic viability of zero-shot molecular design, now available without AI infrastructure or coding expertise at https://platform.latentlabs.com.

q-bio.BM↗

arXiv2025

Latent-X: An Atom-level Frontier Model for De Novo Protein Binder Design

Traditional drug discovery relies on rounds of screening millions of candidate molecules with low success rates, making drug discovery time and resource intensive. To overcome this screening bottleneck, we introduce Latent-X, an all-atom protein design model that enables a new paradigm of precision AI design. Given a target protein epitope, Latent-X jointly generates the all atom structure and sequence of the protein binder and target, directly modelling the non-covalent interactions essential for specific binding. We demonstrate its efficacy across two therapeutically relevant modalities through extensive wet lab experiments, testing as few as 30-100 designs per target. For macrocyclic peptides, Latent-X achieves experimental hit rates exceeding 90% on all evaluated benchmark targets. For mini-binders, it consistently produces potent candidates against all evaluated benchmark targets, with binding affinities reaching the low nanomolar and picomolar range - comparable to those of approved therapeutics - whilst also being highly specific in mammalian display. In direct comparisons with the state-of-the-art models AlphaProteo, RFdiffusion and RFpeptides under identical conditions demonstrates, Latent-X generates binders with higher hit rates and better binding affinities, and uniquely creates structurally diverse binders, including complex beta-sheet folds. Its end-to-end process is an order of magnitude faster than existing multi-step computational pipelines. By drastically improving the efficiency and success rate of de novo design, Latent-X represents a significant advance towards push-button biologics discovery and a valuable tool for protein engineers. Latent-X is available at https://platform.latentlabs.com, enabling users to reliably generate de novo binders without AI infrastructure or coding.

q-bio.BM↗

arXiv2022

Investigating the Impact of Model Misspecification in Neural Simulation-based Inference

Aided by advances in neural density estimation, considerable progress has been made in recent years towards a suite of simulation-based inference (SBI) methods capable of performing flexible, black-box, approximate Bayesian inference for stochastic simulation models. While it has been demonstrated that neural SBI methods can provide accurate posterior approximations, the simulation studies establishing these results have considered only well-specified problems -- that is, where the model and the data generating process coincide exactly. However, the behaviour of such algorithms in the case of model misspecification has received little attention. In this work, we provide the first comprehensive study of the behaviour of neural SBI algorithms in the presence of various forms of model misspecification. We find that misspecification can have a profoundly deleterious effect on performance. Some mitigation strategies are explored, but no approach tested prevents failure in all cases. We conclude that new approaches are required to address model misspecification if neural SBI algorithms are to be relied upon to derive accurate scientific conclusions.

stat.ML↗

arXiv2022

High Performance Simulation for Scalable Multi-Agent Reinforcement Learning

Multi-agent reinforcement learning experiments and open-source training environments are typically limited in scale, supporting tens or sometimes up to hundreds of interacting agents. In this paper we demonstrate the use of Vogue, a high performance agent based model (ABM) framework. Vogue serves as a multi-agent training environment, supporting thousands to tens of thousands of interacting agents while maintaining high training throughput by running both the environment and reinforcement learning (RL) agents on the GPU. High performance multi-agent environments at this scale have the potential to enable the learning of robust and flexible policies for use in ABMs and simulations of complex systems. We demonstrate training performance with two newly developed, large scale multi-agent training environments. Moreover, we show that these environments can train shared RL policies on time-scales of minutes and hours.

cs.MA↗

arXiv2022

Calibrating Agent-based Models to Microdata with Graph Neural Networks

Calibrating agent-based models (ABMs) to data is among the most fundamental requirements to ensure the model fulfils its desired purpose. In recent years, simulation-based inference methods have emerged as powerful tools for performing this task when the model likelihood function is intractable, as is often the case for ABMs. In some real-world use cases of ABMs, both the observed data and the ABM output consist of the agents' states and their interactions over time. In such cases, there is a tension between the desire to make full use of the rich information content of such granular data on the one hand, and the need to reduce the dimensionality of the data to prevent difficulties associated with high-dimensional learning tasks on the other. A possible resolution is to construct lower-dimensional time-series through the use of summary statistics describing the macrostate of the system at each time point. However, a poor choice of summary statistics can result in an unacceptable loss of information from the original dataset, dramatically reducing the quality of the resulting calibration. In this work, we instead propose to learn parameter posteriors associated with granular microdata directly using temporal graph neural networks. We will demonstrate that such an approach offers highly compelling inductive biases for Bayesian inference using the raw ABM microstates as output.

cs.MA↗

arXiv2021

Learning Multimodal VAEs through Mutual Supervision

Multimodal VAEs seek to model the joint distribution over heterogeneous data (e.g.\ vision, language), whilst also capturing a shared representation across such modalities. Prior work has typically combined information from the modalities by reconciling idiosyncratic representations directly in the recognition model through explicit products, mixtures, or other such factorisations. Here we introduce a novel alternative, the MEME, that avoids such explicit combinations by repurposing semi-supervised VAEs to combine information between modalities implicitly through mutual supervision. This formulation naturally allows learning from partially-observed data where some modalities can be entirely missing -- something that most existing approaches either cannot handle, or do so to a limited extent. We demonstrate that MEME outperforms baselines on standard metrics across both partial and complete observation schemes on the MNIST-SVHN (image-image) and CUB (image-text) datasets. We also contrast the quality of the representations learnt by mutual supervision against standard approaches and observe interesting trends in its ability to capture relatedness between data.

cs.LG↗

arXiv2020

Capturing Label Characteristics in VAEs

We present a principled approach to incorporating labels in VAEs that captures the rich characteristic information associated with those labels. While prior work has typically conflated these by learning latent variables that directly correspond to label values, we argue this is contrary to the intended effect of supervision in VAEs-capturing rich label characteristics with the latents. For example, we may want to capture the characteristics of a face that make it look young, rather than just the age of the person. To this end, we develop the CCVAE, a novel VAE model and concomitant variational objective which captures label characteristics explicitly in the latent space, eschewing direct correspondences between label values and latents. Through judicious structuring of mappings between such characteristic latents and labels, we show that the CCVAE can effectively learn meaningful representations of the characteristics of interest across a variety of supervision schemes. In particular, we show that the CCVAE allows for more effective and more general interventions to be performed, such as smooth traversals within the characteristics for a given label, diverse conditional generation, and transferring characteristics across datapoints.

cs.LG↗

arXiv2018

Large Sample Asymptotics of the Pseudo-Marginal Method

The pseudo-marginal algorithm is a variant of the Metropolis--Hastings algorithm which samples asymptotically from a probability distribution when it is only possible to estimate unbiasedly an unnormalized version of its density. Practically, one has to trade-off the computational resources used to obtain this estimator against the asymptotic variances of the ergodic averages obtained by the pseudo-marginal algorithm. Recent works optimizing this trade-off rely on some strong assumptions which can cast doubts over their practical relevance. In particular, they all assume that the distribution of the difference between the log-density and its estimate is independent of the parameter value at which it is evaluated. Under regularity conditions we show here that, as the number of data points tends to infinity, a space-rescaled version of the pseudo-marginal chain converges weakly towards another pseudo-marginal chain for which this assumption indeed holds. A study of this limiting chain allows us to provide parameter dimension-dependent guidelines on how to optimally scale a normal random walk proposal and the number of Monte Carlo samples for the pseudo-marginal method in the large-sample regime. This complements and validates currently available results.

stat.CO↗