No Priors Ep. 121 | With Chai Discovery Co-Founders Jack Dent and Joshua Meier

Background and Formation of Chai Discovery 00:05

  • Chai Discovery was founded by experienced leaders in AI and bioengineering, formerly from Meta, OpenAI, and Stripe.
  • The company was started after founders saw imminent breakthroughs in protein structure prediction and generative modeling, believing the timing was right to commercialize.
  • Unlike traditional AI-bio companies with tight lab integrations, Chai aimed to build a portable, generalizable AI platform for broad application across various drug discovery projects.

Motivation and Opportunity in Drug Discovery 01:06

  • Previous computational approaches in drug discovery showed promising research but lacked practical company timelines.
  • Key inflection point came from advances like AlphaFold 2 in protein folding, which moved from single-protein modeling toward interaction modeling (e.g., antibodies and antigens).
  • Chai's approach leverages diffusion and language models to increase the diversity and quality of generated molecular designs.
  • Chai 1 was open-sourced and widely adopted in industry for structure prediction, setting the stage for Chai 2's more advanced capabilities.

Why Focus on Antibody Discovery and Platform Shift 04:03

  • The potential to engineer molecules with atomic precision presented a massive platform shift affecting not only health but a variety of industries.
  • Antibodies are among the most therapeutically valuable molecules, comprising about 50% of recent drug approvals and 7 of the top 10 bestselling drugs.
  • Chai 2 was launched as a generative model platform to design antibodies, achieving much higher hit rates than previous computational or lab methods.

Technical Breakthrough: Chai 2 Results and Methods 06:12

  • Chai 2 can design effective antibodies against specified targets with a ~20% success rate in just 20 attempts per target, versus previous computational methods (~0.1%) and lab-based approaches (often requiring screening millions of molecules).
  • The benchmark involved 52 problems to demonstrate generalizability, as opposed to typical studies with only a few targets.
  • Model assessment was engineered-centric: used vendor catalogues, ensured held-out data, and focused purely on model performance, not therapeutic relevance.

How the Model Works: Intuitive and Technical Details 12:59

  • At core, structure prediction provides an atomic-resolution “microscope” for 3D protein configurations.
  • The design model receives prompts specifying targets and generates both sequence and 3D structures for antibodies likely to bind the target.
  • Analogy: Structure prediction is like classifying images; generative design is like creating new, fitting “keys” for molecular “locks.”
  • Success rates held even when generalizing to very dissimilar targets, indicating the model learns fundamental interaction principles.

Implications, Industry Impact, and Access 18:20

  • Chai 2 accelerates hit discovery and opens up targets previously inaccessible by traditional methods.
  • Academic groups and companies are being given early access due to overwhelming industry demand.
  • The model challenges reliance on high-throughput screening, potentially complementing or partially replacing large-scale wet lab processes.
  • Combining AI sampling with traditional lab testing could further boost the quality and properties of discovered drugs.

Vision for Biotech’s Future 24:26

  • Despite a gloomy biotech market, Chai 2’s breakthroughs are seen as a sign of an impending industry platform shift.
  • Success rates could rise from 20% toward 50–100% across various molecule classes as models improve.
  • Envisions a future “CAD suite” for biology (analogous to software for engineering or design), fundamentally altering molecule design and drug discovery.
  • This shift may lower risk and diversify targets in drug programs, increasing efficiency and effectiveness across the industry.

Expansion Beyond Antibodies and Further Optimization 27:00

  • Beyond hit rates, other properties like manufacturability and stability will be optimized using the platform.
  • Next-generation antibody formats (e.g., biparatopic antibodies binding multiple epitopes) become easier and faster to create.
  • Approach supports more complex engineering needs, from dual-species cross-reactive molecules to optimizing selectivity and multi-target prompts.

Product Direction, Defensibility, and Investment Areas 31:39

  • Chai 2 is evolving from a research model to a full software product, requiring significant investment in user interface, workflow support, and prompt engineering.
  • Complexities in prompt specification and supporting multiple drug modalities mean the product must enable sophisticated yet accessible workflows for scientists.
  • Continuous learning from lab feedback will help models function as co-pilots, enhancing experimental iteration.

Skills for the Next Generation of Biotech Experts 36:23

  • Antibody engineers and biologists are advised to gain access to Chai 2, master prompt engineering, and explore new experimental possibilities.
  • The shift will require both technical and creative adaptation, similar to how LLMs changed workflows in natural language tasks.
  • Collaboration with domain experts will be crucial due to the vastness and complexity of biological knowledge.

Company Building: Engineering Culture and Team Structure 40:04

  • Chai maintains a highly interdisciplinary, engineering-focused team drawing from biology, chemistry, physics, AI, and computer science.
  • Strong emphasis on modularity, simplicity, and software best practices to avoid technical debt, which is especially important due to the high cost of deep learning errors.
  • Despite a small team (~12 members), intense focus and collaboration drive the company’s rapid progress.
  • Investment in platform engineering from the outset is seen as essential for scaling and speed of innovation.

Resource Allocation and Growth Strategy 46:42

  • The company began with scrappy resource use (leveraging free compute credits) and remains disciplined about compute investment, scaling only when justified by results.
  • The focus is on rapid progress, prioritizing key problems, and being smart about spending amid fast-moving advances in the field.
  • Chai is hiring across all key functions, including engineering, antibody discovery, business development, and product roles to meet surging industry demand.

Closing and Contact Information 49:00

  • The co-founders express optimism about the impact of their work and encourage interested parties to follow their updates and apply for early access or open roles.
  • Listeners are directed to No Priors’ podcast and website for more information and transcripts.