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Dec 12, 2023 · 24m · a16z

Big Ideas in 2024: Programming Medicine’s Final Frontier with Jorge Conde

Jorge Conde · 16m spoken
0:00 / 0:00
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In this episode of a16z's 'Big Ideas in 2024' series, General Partner Jorge Conde explains how programmable medicine and reusable biological delivery platforms are revolutionizing therapeutic development to deliver scalable, curative treatments.

How this conversation actually went

Every chapter scored 0–10 on four independent dynamics. Hover any point for the reasoning behind the score. How this is scored →

The host as informed peer 1.5 Guest teaching 2.8 Guest disagreement 0.2 The host pushing back 0.3
05100:0010:0020:000:00–3:05 · The host as informed peer 0/10 Recap of 2023 Tech Predictions Introductory promotional segment and guest pitch monologue establishing the A16Z Big Ideas list and introducing the reusable rocket biotech analogy.3:05–6:43 · The host as informed peer 1/10 The Timeline and Risks of Traditional Drug Development The host asks broad setup questions about traditional drug timelines. The guest provides an educational breakdown of the drug discovery, preclinical, and clinical trial phases.6:43–10:42 · The host as informed peer 2/10 How Programmable Medicine Transforms Drug Discovery The host paraphrases the guest's reusable rocket analogy to confirm comprehension. The guest elaborates on delivery vectors like LNPs and AAVs.10:42–16:00 · The host as informed peer 1/10 FDA Agility and the Historic CRISPR Milestone The guest details regulatory adaptations at the FDA and highlights the historic landmark approval of the Vertex/CRISPR therapy for sickle cell anemia.16:00–22:59 · The host as informed peer 2/10 Patient Impact, Industry Blockers, and Opportunities for Builders The host prompts a discussion on potential failure points and blockers. The guest explains permanent genetic modification risks, clinical friction, and multi-million dollar treatment costs.22:59–23:42 · The host as informed peer 3/10 Exponential Scaling and Cost Reduction in Biology The host draws a connection to tech exponential cost curves. The guest acknowledges the biological potential while gently grounding expectations that it has not happened yet.0:00–3:05 · Guest teaching 0/10 Recap of 2023 Tech Predictions Introductory promotional segment and guest pitch monologue establishing the A16Z Big Ideas list and introducing the reusable rocket biotech analogy.3:05–6:43 · Guest teaching 4/10 The Timeline and Risks of Traditional Drug Development The host asks broad setup questions about traditional drug timelines. The guest provides an educational breakdown of the drug discovery, preclinical, and clinical trial phases.6:43–10:42 · Guest teaching 3/10 How Programmable Medicine Transforms Drug Discovery The host paraphrases the guest's reusable rocket analogy to confirm comprehension. The guest elaborates on delivery vectors like LNPs and AAVs.10:42–16:00 · Guest teaching 4/10 FDA Agility and the Historic CRISPR Milestone The guest details regulatory adaptations at the FDA and highlights the historic landmark approval of the Vertex/CRISPR therapy for sickle cell anemia.16:00–22:59 · Guest teaching 4/10 Patient Impact, Industry Blockers, and Opportunities for Builders The host prompts a discussion on potential failure points and blockers. The guest explains permanent genetic modification risks, clinical friction, and multi-million dollar treatment costs.22:59–23:42 · Guest teaching 2/10 Exponential Scaling and Cost Reduction in Biology The host draws a connection to tech exponential cost curves. The guest acknowledges the biological potential while gently grounding expectations that it has not happened yet.0:00–3:05 · Guest disagreement 0/10 Recap of 2023 Tech Predictions Introductory promotional segment and guest pitch monologue establishing the A16Z Big Ideas list and introducing the reusable rocket biotech analogy.3:05–6:43 · Guest disagreement 0/10 The Timeline and Risks of Traditional Drug Development The host asks broad setup questions about traditional drug timelines. The guest provides an educational breakdown of the drug discovery, preclinical, and clinical trial phases.6:43–10:42 · Guest disagreement 0/10 How Programmable Medicine Transforms Drug Discovery The host paraphrases the guest's reusable rocket analogy to confirm comprehension. The guest elaborates on delivery vectors like LNPs and AAVs.10:42–16:00 · Guest disagreement 0/10 FDA Agility and the Historic CRISPR Milestone The guest details regulatory adaptations at the FDA and highlights the historic landmark approval of the Vertex/CRISPR therapy for sickle cell anemia.16:00–22:59 · Guest disagreement 0/10 Patient Impact, Industry Blockers, and Opportunities for Builders The host prompts a discussion on potential failure points and blockers. The guest explains permanent genetic modification risks, clinical friction, and multi-million dollar treatment costs.22:59–23:42 · Guest disagreement 1/10 Exponential Scaling and Cost Reduction in Biology The host draws a connection to tech exponential cost curves. The guest acknowledges the biological potential while gently grounding expectations that it has not happened yet.0:00–3:05 · The host pushing back 0/10 Recap of 2023 Tech Predictions Introductory promotional segment and guest pitch monologue establishing the A16Z Big Ideas list and introducing the reusable rocket biotech analogy.3:05–6:43 · The host pushing back 1/10 The Timeline and Risks of Traditional Drug Development The host asks broad setup questions about traditional drug timelines. The guest provides an educational breakdown of the drug discovery, preclinical, and clinical trial phases.6:43–10:42 · The host pushing back 0/10 How Programmable Medicine Transforms Drug Discovery The host paraphrases the guest's reusable rocket analogy to confirm comprehension. The guest elaborates on delivery vectors like LNPs and AAVs.10:42–16:00 · The host pushing back 0/10 FDA Agility and the Historic CRISPR Milestone The guest details regulatory adaptations at the FDA and highlights the historic landmark approval of the Vertex/CRISPR therapy for sickle cell anemia.16:00–22:59 · The host pushing back 1/10 Patient Impact, Industry Blockers, and Opportunities for Builders The host prompts a discussion on potential failure points and blockers. The guest explains permanent genetic modification risks, clinical friction, and multi-million dollar treatment costs.22:59–23:42 · The host pushing back 0/10 Exponential Scaling and Cost Reduction in Biology The host draws a connection to tech exponential cost curves. The guest acknowledges the biological potential while gently grounding expectations that it has not happened yet.

speaking balance: gold is the host, purple is the guest (3 minute bins)

0:00 · the host 0% · guest 100%0:00 · the host 0% · guest 100%3:00 · the host 0% · guest 100%3:00 · the host 0% · guest 100%6:00 · the host 0% · guest 100%6:00 · the host 0% · guest 100%9:00 · the host 0% · guest 100%9:00 · the host 0% · guest 100%12:00 · the host 0% · guest 100%12:00 · the host 0% · guest 100%15:00 · the host 0% · guest 100%15:00 · the host 0% · guest 100%18:00 · the host 0% · guest 100%18:00 · the host 0% · guest 100%21:00 · the host 0% · guest 100%21:00 · the host 0% · guest 100%24:00 · the host 0% · guest 100%24:00 · the host 0% · guest 100%
Sharpest disagreement ▶ 23:24 Tempering tech cost curve expectations

The guest gently refutes the immediate assumption of software-style cost reductions by emphasizing that exponential cost drops in biology remain an unproven hope rather than a current reality.

 Hardest push from the host ▶ 17:45 Challenging the rosy outlook

The host pushes past the optimistic narrative to demand a candid discussion on industry blockers, regulatory barriers, and reasons why the vision might fail.

 Biggest teaching moment ▶ 20:56 Explaining the economics of gene therapy

The guest educates on the severe financial realities of advanced therapies, citing multi-million dollar price tags like $2.1M for SMA therapies and why manufacturing creates extreme bottlenecks.

 The host holds their own ▶ 22:59 Framing via tech industry cost curves

The host demonstrates domain synthesis by drawing a parallel between tech industry Wright's Law exponential cost reduction curves and biological manufacturing.
the scores for every segment, with the reasoning behind each
ChapterTopicThe host as informed peerGuest teachingGuest disagreementThe host pushing backWhy
Recap of 2023 Tech Predictions 0000 Introductory promotional segment and guest pitch monologue establishing the A16Z Big Ideas list and introducing the reusable rocket biotech analogy.
The Timeline and Risks of Traditional Drug Development 1401 The host asks broad setup questions about traditional drug timelines. The guest provides an educational breakdown of the drug discovery, preclinical, and clinical trial phases.
How Programmable Medicine Transforms Drug Discovery 2300 The host paraphrases the guest's reusable rocket analogy to confirm comprehension. The guest elaborates on delivery vectors like LNPs and AAVs.
FDA Agility and the Historic CRISPR Milestone 1400 The guest details regulatory adaptations at the FDA and highlights the historic landmark approval of the Vertex/CRISPR therapy for sickle cell anemia.
Patient Impact, Industry Blockers, and Opportunities for Builders 2401 The host prompts a discussion on potential failure points and blockers. The guest explains permanent genetic modification risks, clinical friction, and multi-million dollar treatment costs.
Exponential Scaling and Cost Reduction in Biology 3210 The host draws a connection to tech exponential cost curves. The guest acknowledges the biological potential while gently grounding expectations that it has not happened yet.

Statements from this episode (8)

Insight
Legacy drug development is inefficient and single-use like old rockets
“Traditional drug development is painstakingly time-consuming, risky, and expensive. It's highly bespoke too. One molecule has no bearing on the next molecule that gets developed. Like traditional rockets, they're one-time use only.”
Jorge Conde Dec 12, 2023 ▶ 1:55
Assertion Supported
FDA creates new office and Warp Speed pilot for rare diseases
“The FDA is looking to the skies and taking a page out of the FAA's approach to aviation safety, rigorous yet adaptive. Recently launching its own new office for therapeutic products and piloting Operation Warp Speed for rare disease to create more transparent …”
Jorge Conde Dec 12, 2023 ▶ 2:36
Assertion Supported
Developing a new drug takes 10 to 15 years on average
“These are averages of averages, of course, but on average, it could take anywhere between 10 to 15 years to develop a drug to get it to patients.”
Jorge Conde Dec 12, 2023 ▶ 3:51
Insight
Gene therapy delivery platforms enable modular repurposing across different diseases
“If we're able to make a medicine that does that, that can deliver one gene to a given cell type, it becomes increasingly likely that we'll be able to deliver a different gene to a different cell type for a different disease.”
Jorge Conde Dec 12, 2023 ▶ 7:19
Assertion Supported
FDA approves first CRISPR gene editing therapy for sickle cell anemia
“The breaking news is that the first CRISPR therapy has been approved. This is a therapy for sickle cell anemia and beta thalassemia that was developed by a biopharmaceutical company called Vertex Pharmaceuticals, working with another company called CRISPR Ther…”
Jorge Conde Dec 12, 2023 ▶ 13:58
Assertion Supported
CRISPR progressed from initial discovery to FDA approval in just 10 years
“It's barely been 10 years since the concept of CRISPR was discovered and described in the scientific literature. So we went from the initial discovery of CRISPR as a potential use as a medicine, all the way to an approval in just over 10 years. That is lightni…”
Jorge Conde Dec 12, 2023 ▶ 15:30
Assertion Supported
Novartis's one-time gene therapy for spinal muscular atrophy costs $2.1 million
“You know, in the case of treating a baby that had, you know, something like somatic muscular atrophy that would have otherwise died, a one and done gene therapy from Novartis, this is a therapy that's worth about, it's cost about 2.1 million dollars, effective…”
Jorge Conde Dec 12, 2023 ▶ 21:23
Insight
Biology is the most scalable technology on Earth
“If there is one technology on this planet that can scale better than anything else we know of, it's biology.”
Jorge Conde Dec 12, 2023 ▶ 22:01
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