
Written by a model from the transcript; not yet reviewed.
This episode of This Week in Startups features a VC roundtable hosted by a guest moderator from Menlo Ventures, joined by panelists from Coastal Ventures, Signalfire, and Better Tomorrow Ventures. The discussion centers on recent breakthroughs in AI, particularly OpenAI's advanced math results covering several millennium prize problems, and what these compounding capabilities mean for early-stage investing. The panel debates the dominance of compute-rich frontier labs versus vertical AI startups that own proprietary data workflows, noting how younger, AI-native founders are leveraging autonomous agents to rewrite traditional software playbooks.
Moving to consumer AI, the guests analyze the high valuations and utility of personal agents like Instinct and Muse, weighing the advantage of platform distribution against privacy concerns and high costs. They also dissect the dynamics of competitive investments in fast-moving AI categories, the state of enterprise SaaS amid multiple compression, and how venture capitalists are adapting their research methods to keep pace with rapid technological change.
The host introduces the roundtable, announces the guest moderator and the panelists.
The host promotes the Plod note pin and its AI-generated transcript capabilities.
Panelists discuss the significance of recent OpenAI mathematical results and their investment implications.
Investors explore how AI advances could accelerate breakthroughs in medicine and planetary health.
Discussion on how the definition of a strong founder has evolved with AI-enabled startups.
The panel debates current compute limitations, future scaling, and the role of physical AI labs.
Panelists weigh the prospects and risks of personal AI agents like Instinct and Muse.
Discussion of how personal AI agents can streamline personal finance tasks and reduce administrative friction.
Speaker 02 shares a privacy incident involving an AI agent leaking bank information, raising trust issues.
A viral tweet imagines AI agents advising users to withdraw funds, potentially triggering bank runs and systemic risk.
Exploration of how AI agents could lower friction in insurance, banking, and other bureaucratic processes.
The panel discusses a Twitter feud between Factory and Cognition, its origins, and its impact on investor perception.
OpenAI Math Breakthroughsinsight
The panel discusses recent mathematical results from OpenAI that solve major problems across four remaining unsolved millennium prize domains, highlighting how AI capabilities are compounding rapidly across formal and informal sciences.
Healthcare And Life Sciencesinsight
The guest explains how converging investments in life sciences, automated wet labs, and data capture will drive unprecedented breakthroughs in understanding complex human biology and planetary health.
Compute Constraints And Efficiencydebate
The moderator questions whether startups can compete given massive compute concentration in labs like OpenAI and Anthropic, prompting a discussion on algorithmic efficiencies and alternative scaling paths.
Data Companies Terminal Valuedebate
The panel disagrees on whether data providers to AI labs have long-term terminal value, with one investor arguing that foundation models eventually internalize needed data while another emphasizes founder adaptability.
The Rise Of Young Hackersstrategy
An investor describes a bimodal investment strategy that pairs deep domain experts with young, insatiably curious hacker founders who are unburdened by legacy industry constraints.
Real World Agent Use Casesstory
The guest moderator shares a concrete personal success story of using an AI personal agent to navigate flight delays and automatically secure a 600 euro EU refund.
Factory Versus Cognition Dramadebate
The panel addresses the viral public spat between coding agent startups Factory and Cognition, touching on the complexities of venture capital firms investing in competing companies.
SaaS Multiples And Labor TAMinsight
The discussion examines public market multiple compression for 2010s SaaS darlings, explaining how AI expands the addressable market by going after labor rather than just software budgets.
“We at Coastal Ventures are very proud early investors in OpenAI, and I'm very excited about all the results.”
“I think a lot of what I've seen with other people and certainly applies to myself is there's only so many points of entry into my private data that I want.”
“I think it's a really interesting time for sort of young founders. Because you can also do so much with so little money, much like what cloud computing did.”
“On top of it, I'm, I'm also really bullish on personal finance use cases because it's like the bane of my existence of like,”
“I think there's a lot of systems in the world that are built on breakage.”
This Week In Startups is made possible by: Plaud: http://Plaud.ai/twist Odoo: http://Odoo.com/twist Northwest Registered Agent: http://www.northwestregisteredagent.com/twistdomain Quo: https://www.quo.com/perks/twist Today’s show: A personal AI agent that’s still invite-only just hit a $10 billion valuation. Guest host Deedy Das of Menlo Ventures is joined by Kanu Gulati of Khosla Ventures, Chris Farmer of SignalFire, and Sheel Mohnot of Better Tomorrow Ventures to debate whether Instinct can beat Meta’s Muse, what they actually use their own agents for, and what breaks when everyone’s agent makes the same move. Plus we’re also talking about OpenAI’s math breakthroughs, the Factory vs. Cognition fight, and whether SaaS is still worth funding. Catch the whole debate on this week’s VC roundtable. Guests: Deedy Das on X: https://x.com/deedydas Menlo Ventures: https://menlovc.com Kanu Gulati on X: https://x.com/KanuGulati Khosla Ventures: https://www.khoslaventures.com Chris Farmer on X: https://x.com/chriswfarmer SignalFire: https://www.signalfire.com Sheel Mohnot on X: https://x.com/pitdesi Better Tomorrow Ventures: https://www.btv.vc Relevant Links: OpenAI’s 722 math manuscripts from an unreleased internal model → https://github.com/openai/math OpenAI’s earlier Navier–Stokes Millennium Prize result → https://openai.com/index/navier-stokes-solution/ Pramaana Labs, the Khosla-backed startup turning tax rules into provable logic → https://pramaanalabs.ai Logos Research, the Imperial College spinout verifying AI-written financial code → https://www.imperial.ac.uk/news/articles/2026/logos-research-plans-to-make-ai-reasoning-trustworthy-in-high-stakes-environments/ EvenUp, SignalFire’s AI company for personal injury law → https://www.evenuplaw.com/ WindBorne Systems, the Khosla-backed weather balloon company Kanu mentioned → https://windbornesystems.com Gokul Rajaram’s X Post: https://x.com/gokulr/status/2107851356019290569?s=20 micro1, the AI training data company Chris and LAUNCH backs → https://www.micro1.ai Vercel’s data on companies shifting to open-weight models → https://vercel.com/i/open-weight-models Instinct raises $1B at a $10B valuation (SiliconANGLE) → https://siliconangle.com/2026/09/28/everyday-personal-ai-assistant-startup-instinct-raises-1b-at-10b-valuation/ Meta introduces Muse, its personal AI agent → https://about.fb.com/news/2026/09/introducing-muse-personal-ai-agent/ Wajo, maker of the Fo agent Kanu uses → https://wajo.ai Factory’s CEO accuses his board adviser of spying for Cognition (TechCrunch) → https://techcrunch.com/2026/09/30/factory-ceo-just-accused-his-vc-board-advisor-of-spying-for-cognition/ xAI rents its Colossus 1 data center to Anthropic (Data Center Dynamics) → https://www.datacenterdynamics.com/en/news/musk-spacex-xai-is-actively-seeking-more-ai-compute-customers-following-anthropic-deal/ Bending Spoons agrees to buy Miro, weeks after Airtable → https://investors.bendingspoons.com/newsroom/bending-spoons-agrees-to-acquire-miro The FCC’s new rule on foreign-made robots → https://www.fcc.gov/covered-list-faqs-robots-inverters Timestamps: 0:00 VC roundtable with guest host Deedy Das 1:23 If your work depends on conversations - interviews, meetings, calls - you need a Plaud NotePin S. You can check it out at https://Plaud.ai/twist and use code TWIST for 10% off! 2:11 OpenAI's math results and what's left to invest in 5:10 Formalizing taxes and code so AI can prove its work 6:37 Why science breakthroughs still need the real world 9:44 Odoo: The all-in-one business platform. Your first app is free! Get started today at https://Odoo.com/twist 10:54 Can startups compete with the labs on compute? 13:02 Private data and vertical AI as the moat 18:54 Would you invest in AI training data companies? 20:34 Got a new business idea? Northwest Registered Agent helps you bring it to life. Get a free domain, email, phone number, and more - with no purchase required! - Learn more at www.northwestregisteredagent.com/twistdomain 26:29 What a great founder looks like in the AI era 29:13 Quo (formerly OpenPhone) gives you a clean, modern way to handle every customer call, text, and thread all in one place. Try it free at https://quo.com/TWiST 34:35 Is Instinct worth $10 billion? 41:31 Can Muse reach a billion daily users? 44:49 Favorite personal agent use cases 49:06 What happens when everyone's agent makes the same call 53:17 Factory vs. Cognition and VCs backing rivals 1:03:49 Is SaaS still worth venture money? 1:09:49 Where the panel gets its information 1:14:45 What a seed fund means in 2026 Subscribe to our newsletters on Substack: TWiST: https://twistartups.substack.com/ TWiAI: https://www.thisweekinai.ai/ TWiVC: https://thisweekinvc.substack.com/ Subscribe to This Week in Startups on Apple: https://rb.gy/v19fcp Follow Lon: X: https://x.com/lons Follow Jason: X: https://twitter.com/Jason LinkedIn: https://www.linkedin.com/in/jasoncalacanis Thank you to our partners: Check out all our partner offers: https://partners.launch.co/
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