VCs Would Bet on Open-Source AI Over OpenAI and Anthropic | E2341

This Week In Startups is made possible by: Northwest Registered Agent: https://www.northwestregisteredagent.com/twistdomain Odoo: http://Odoo.com/twist Rippling: http://Rippling.ai/twist Plaud: http://Plaud.ai/twist Harmonic: http://harmonic.ai/ Today’s show: Anthropic and OpenAI released cheaper models on the same day with Claude Opus 5.5 and GPT-6, and these VCs would still bet on open source. Jason brings on Dave McClure of Practical Venture Capital, Jeff Clavier of Uncork Capital, and Jenny Fielding of Everywhere Ventures to discuss the argument for open-weight models over the frontier labs. Learn why median seed valuations have more than tripled since 2017. Why does Dave say it's a buyer's market for secondaries right now? PLUS, does Meta's Muse leave any room for Instinct, and why are fintech and healthcare suddenly out of favor? Guests: Dave McClure on X: https://x.com/davemcclure?lang=en Practical Venture Capital: https://practicalvc.com/ Jeff Clavier on X: https://x.com/jeff Uncorked Capital: https://uncorkcapital.com/ Jenny Fiedling on X: https://x.com/jefielding Everywhere Ventures: https://www.everywhere.vc/ Relevant Links: Instinct reportedly seeking $1B at a $10B valuation (report via The Information) → https://cryptobriefing.com/ai-assistant-startup-instinct-targets-10b-valuation-in-new-funding-talks-report/ Meta's Muse, the agent the panel sees as Instinct's biggest threat, now on Mac → https://aiweekly.co/alerts/meta-ships-muse-for-mac-agent-now-acts-in-native-macos-apps Trump calls Jensen Huang onstage at the All-In Summit → https://thenextweb.com/news/trump-phoned-jensen-huang-onstage-at-the-all-in-summit-to-call-ai-fear-a-hoax AI-assisted intel error nearly triggered a US intercept of a Chinese ship (CNN via gCaptain) → https://gcaptain.com/ai-error-nearly-triggered-u-s-intercept-of-chinese-ship-cnn-reports/ Bernie Sanders' 50% AI sovereign wealth fund bill + Altman meeting (Fortune) → https://fortune.com/2026/06/18/bernie-sanders-ai-fund-bill-sam-altman-1000-payments/ Stanley Druckenmiller's AI-written WSJ op-ed (Axios) → https://axios.com/2026/08/26/stanley-druckenmiller-ai-writing-wsj-op-ed Claude Opus 5.5 and GPT-6 Sol/Luna launch the same day with price cuts (SiliconANGLE) → https://siliconangle.com/2026/09/22/anthropic-releases-claude-opus-5-5-and-openai-counters-with-two-cheaper-gpt-6-models/ Zipline: LAUNCH's "miss," later backed through the syndicate → https://www.flyzipline.com/ Micro1 → https://www.micro1.ai/ Founder University → **https://www.founder.university/** [VERIFY] The Syndicate: angel invest alongside LAUNCH (apply, waitlist) → **https://thesyndicate.com/** Timestamps: 0:00 What seed rounds looked like then: Fitbit's $2M seed 2:38 Jenny's Techstars NYC years and the two-unicorn mug 6:10 Plaud: 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! 7:51 All-In Summit: Trump calls Jensen Huang onstage. Staged or not? 8:56 P(doom) roundtable + Dave's AI sovereign wealth fund prediction 10:08 Northwest Registered Agent - 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 https://www.northwestregisteredagent.com/twistdomain 13:35 The AI intel error that nearly triggered a US-China incident 17:44 "McClure's Law": a human with AI is the real risk 19:59 Odoo - The all-in-one business platform. Your first app is free! Get started today at https://Odoo.com/twist 21:37 Stripe + OpenRouter: an anti-fraud play, not a routing play? 23:07 Seed valuations: median $8M (2017) to $28M today 23:58 Instinct: $2.5B to a reported $10B in weeks 29:49 Rippling - Thanks to our partners at Rippling! Head to https://Rippling.ai/twist and get the only AI built to give you full visibility across your startup and take complex actions across your entire business. 44:01 Opus 5.5 vs. GPT-6 Sol: the same-day price war 46:51 Gun to your head: open-weight models or frontier labs? 51:00 Secondaries: the top 30 names vs. everyone else 52:30 Why fintech and healthcare are unloved (and Jason's Robinhood bet) Subscribe to the TWiST500 newsletter: https://ticker.thisweekinstartups.com Check out the TWIST500: https://www.twist500.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: (0:00) PARTNER - AD BLURB (0:00) PARTNER - AD BLURB (0:00) PARTNER - AD BLURB Check out all our partner offers: https://partners.launch.co/ Great TWIST interviews: Will Guidara, Eoghan McCabe, Steve Huffman, Brian Chesky, Bob Moesta, Aaron Levie, Sophia Amoruso, Reid Hoffman, Frank Slootman, Billy McFarland Subscribe to our Substack Newsletters! 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