Oct 6, 2022 · 51m · capital-allocators

Andy Acker - Empty Rooms: Investing in Biotech at Janus Henderson (Capital Allocators, EP.274)

Andy Acker · 42m spoken Ted Seides · 5m spoken
0:00 / 0:00

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Andy Acker, Lead Portfolio Manager at Janus Henderson Investors, discusses the fundamental dynamics, investment frameworks, and contrarian opportunities within the biotechnology sector following historic market drawdowns. He outlines how specialized scientific research, rigorous clinical and commercial risk management, and disciplined portfolio construction enable investors to capitalize on a golden age of medical breakthroughs.

How this conversation actually went

Every chapter scored 0–10 on four independent dynamics. Hover any point for the reasoning behind the score. Ted holds 10.9% of the talking time here. How this is scored →

Ted as informed peer 2.5 Guest teaching 5.1 Guest disagreement 0.1 Ted pushing back 0.0
05100:0015:0030:0045:002:17–4:39 · Ted as informed peer 2/10 Andy Acker's Background and Path to Janus Henderson Ted opens with friendly biographical prompts acknowledging their shared business school background. Andy shares his personal journey from a family of doctors to biotech investing at Janus Henderson in an entirely collaborative tone.4:40–10:20 · Ted as informed peer 2/10 A Quarter Century of Scientific Breakthroughs in Medicine Ted prompts Andy on the evolution of biotech science over his career. Andy delivers an educational overview comparing the 13-year Human Genome Project to modern sequencing, mRNA vaccines, antibody drug conjugates, and gene therapies.10:21–18:41 · Ted as informed peer 3/10 The 90/90 Rule and the Three Ps Framework Andy introduces his core investment framework: the 90/90 rule (clinical trial failure rates and Wall Street consensus estimation error) alongside the Three Ps (physicians, patients, payers). Ted follows up with concise clarifying questions on the two sides of the rule.18:42–24:18 · Ted as informed peer 3/10 Biotech Market Volatility and the 2021-2022 Bear Market Ted asks how idiosyncratic drug risk maps onto broad sector drawdowns. Andy details the historic 2021–2022 bear market, explaining how 200 companies ended up trading below cash and differentiating early development from early commercial firms.24:18–32:13 · Ted as informed peer 3/10 Fundamental Research Process and Management Evaluation Ted probes how much management quality matters versus the underlying science. Andy shares a real-world case study of Global Blood Therapeutics, noting that underestimating management was one of the biggest lessons of his career.32:14–38:34 · Ted as informed peer 3/10 Portfolio Construction, Sizing, and Trading Strategies Andy details his barbell portfolio structure, strictly capping binary risk to 100-200 basis points and rebalancing against intrinsic DCF valuations. Ted guides the technical discussion with questions on position sizing and behavioral trading.38:35–44:07 · Ted as informed peer 2/10 Crossover Investing and High-Conviction Therapeutic Themes Andy explains the strategic advantage of private crossover investing (e.g., early BioNTech backing) and outlines major clinical frontiers in NASH, gene therapy, and incretin-based obesity treatments.44:08–47:58 · Ted as informed peer 2/10 Industry Risks and Green Shoots in the Biotech Sector Andy analyzes policy risk from the Inflation Reduction Act and points to green shoots like corporate cash piles and M&A necessity as catalysts for a sector rebound before transitioning to lighthearted concluding questions.2:17–4:39 · Guest teaching 1/10 Andy Acker's Background and Path to Janus Henderson Ted opens with friendly biographical prompts acknowledging their shared business school background. Andy shares his personal journey from a family of doctors to biotech investing at Janus Henderson in an entirely collaborative tone.4:40–10:20 · Guest teaching 6/10 A Quarter Century of Scientific Breakthroughs in Medicine Ted prompts Andy on the evolution of biotech science over his career. Andy delivers an educational overview comparing the 13-year Human Genome Project to modern sequencing, mRNA vaccines, antibody drug conjugates, and gene therapies.10:21–18:41 · Guest teaching 7/10 The 90/90 Rule and the Three Ps Framework Andy introduces his core investment framework: the 90/90 rule (clinical trial failure rates and Wall Street consensus estimation error) alongside the Three Ps (physicians, patients, payers). Ted follows up with concise clarifying questions on the two sides of the rule.18:42–24:18 · Guest teaching 6/10 Biotech Market Volatility and the 2021-2022 Bear Market Ted asks how idiosyncratic drug risk maps onto broad sector drawdowns. Andy details the historic 2021–2022 bear market, explaining how 200 companies ended up trading below cash and differentiating early development from early commercial firms.24:18–32:13 · Guest teaching 5/10 Fundamental Research Process and Management Evaluation Ted probes how much management quality matters versus the underlying science. Andy shares a real-world case study of Global Blood Therapeutics, noting that underestimating management was one of the biggest lessons of his career.32:14–38:34 · Guest teaching 5/10 Portfolio Construction, Sizing, and Trading Strategies Andy details his barbell portfolio structure, strictly capping binary risk to 100-200 basis points and rebalancing against intrinsic DCF valuations. Ted guides the technical discussion with questions on position sizing and behavioral trading.38:35–44:07 · Guest teaching 6/10 Crossover Investing and High-Conviction Therapeutic Themes Andy explains the strategic advantage of private crossover investing (e.g., early BioNTech backing) and outlines major clinical frontiers in NASH, gene therapy, and incretin-based obesity treatments.44:08–47:58 · Guest teaching 5/10 Industry Risks and Green Shoots in the Biotech Sector Andy analyzes policy risk from the Inflation Reduction Act and points to green shoots like corporate cash piles and M&A necessity as catalysts for a sector rebound before transitioning to lighthearted concluding questions.2:17–4:39 · Guest disagreement 0/10 Andy Acker's Background and Path to Janus Henderson Ted opens with friendly biographical prompts acknowledging their shared business school background. Andy shares his personal journey from a family of doctors to biotech investing at Janus Henderson in an entirely collaborative tone.4:40–10:20 · Guest disagreement 0/10 A Quarter Century of Scientific Breakthroughs in Medicine Ted prompts Andy on the evolution of biotech science over his career. Andy delivers an educational overview comparing the 13-year Human Genome Project to modern sequencing, mRNA vaccines, antibody drug conjugates, and gene therapies.10:21–18:41 · Guest disagreement 0/10 The 90/90 Rule and the Three Ps Framework Andy introduces his core investment framework: the 90/90 rule (clinical trial failure rates and Wall Street consensus estimation error) alongside the Three Ps (physicians, patients, payers). Ted follows up with concise clarifying questions on the two sides of the rule.18:42–24:18 · Guest disagreement 1/10 Biotech Market Volatility and the 2021-2022 Bear Market Ted asks how idiosyncratic drug risk maps onto broad sector drawdowns. Andy details the historic 2021–2022 bear market, explaining how 200 companies ended up trading below cash and differentiating early development from early commercial firms.24:18–32:13 · Guest disagreement 0/10 Fundamental Research Process and Management Evaluation Ted probes how much management quality matters versus the underlying science. Andy shares a real-world case study of Global Blood Therapeutics, noting that underestimating management was one of the biggest lessons of his career.32:14–38:34 · Guest disagreement 0/10 Portfolio Construction, Sizing, and Trading Strategies Andy details his barbell portfolio structure, strictly capping binary risk to 100-200 basis points and rebalancing against intrinsic DCF valuations. Ted guides the technical discussion with questions on position sizing and behavioral trading.38:35–44:07 · Guest disagreement 0/10 Crossover Investing and High-Conviction Therapeutic Themes Andy explains the strategic advantage of private crossover investing (e.g., early BioNTech backing) and outlines major clinical frontiers in NASH, gene therapy, and incretin-based obesity treatments.44:08–47:58 · Guest disagreement 0/10 Industry Risks and Green Shoots in the Biotech Sector Andy analyzes policy risk from the Inflation Reduction Act and points to green shoots like corporate cash piles and M&A necessity as catalysts for a sector rebound before transitioning to lighthearted concluding questions.2:17–4:39 · Ted pushing back 0/10 Andy Acker's Background and Path to Janus Henderson Ted opens with friendly biographical prompts acknowledging their shared business school background. Andy shares his personal journey from a family of doctors to biotech investing at Janus Henderson in an entirely collaborative tone.4:40–10:20 · Ted pushing back 0/10 A Quarter Century of Scientific Breakthroughs in Medicine Ted prompts Andy on the evolution of biotech science over his career. Andy delivers an educational overview comparing the 13-year Human Genome Project to modern sequencing, mRNA vaccines, antibody drug conjugates, and gene therapies.10:21–18:41 · Ted pushing back 0/10 The 90/90 Rule and the Three Ps Framework Andy introduces his core investment framework: the 90/90 rule (clinical trial failure rates and Wall Street consensus estimation error) alongside the Three Ps (physicians, patients, payers). Ted follows up with concise clarifying questions on the two sides of the rule.18:42–24:18 · Ted pushing back 0/10 Biotech Market Volatility and the 2021-2022 Bear Market Ted asks how idiosyncratic drug risk maps onto broad sector drawdowns. Andy details the historic 2021–2022 bear market, explaining how 200 companies ended up trading below cash and differentiating early development from early commercial firms.24:18–32:13 · Ted pushing back 0/10 Fundamental Research Process and Management Evaluation Ted probes how much management quality matters versus the underlying science. Andy shares a real-world case study of Global Blood Therapeutics, noting that underestimating management was one of the biggest lessons of his career.32:14–38:34 · Ted pushing back 0/10 Portfolio Construction, Sizing, and Trading Strategies Andy details his barbell portfolio structure, strictly capping binary risk to 100-200 basis points and rebalancing against intrinsic DCF valuations. Ted guides the technical discussion with questions on position sizing and behavioral trading.38:35–44:07 · Ted pushing back 0/10 Crossover Investing and High-Conviction Therapeutic Themes Andy explains the strategic advantage of private crossover investing (e.g., early BioNTech backing) and outlines major clinical frontiers in NASH, gene therapy, and incretin-based obesity treatments.44:08–47:58 · Ted pushing back 0/10 Industry Risks and Green Shoots in the Biotech Sector Andy analyzes policy risk from the Inflation Reduction Act and points to green shoots like corporate cash piles and M&A necessity as catalysts for a sector rebound before transitioning to lighthearted concluding questions.

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

0:00 · Ted 69.5% · guest 30.5%0:00 · Ted 69.5% · guest 30.5%3:00 · Ted 12.1% · guest 87.9%3:00 · Ted 12.1% · guest 87.9%6:00 · Ted 0% · guest 100%6:00 · Ted 0% · guest 100%9:00 · Ted 3.4% · guest 96.6%9:00 · Ted 3.4% · guest 96.6%12:00 · Ted 3.6% · guest 96.4%12:00 · Ted 3.6% · guest 96.4%15:00 · Ted 0% · guest 100%15:00 · Ted 0% · guest 100%18:00 · Ted 20.4% · guest 79.6%18:00 · Ted 20.4% · guest 79.6%21:00 · Ted 0% · guest 100%21:00 · Ted 0% · guest 100%24:00 · Ted 7.2% · guest 92.8%24:00 · Ted 7.2% · guest 92.8%27:00 · Ted 15.7% · guest 84.3%27:00 · Ted 15.7% · guest 84.3%30:00 · Ted 6.3% · guest 93.7%30:00 · Ted 6.3% · guest 93.7%33:00 · Ted 2.2% · guest 97.8%33:00 · Ted 2.2% · guest 97.8%36:00 · Ted 11.1% · guest 88.9%36:00 · Ted 11.1% · guest 88.9%39:00 · Ted 5.2% · guest 94.8%39:00 · Ted 5.2% · guest 94.8%42:00 · Ted 1.6% · guest 98.4%42:00 · Ted 1.6% · guest 98.4%45:00 · Ted 4.3% · guest 95.7%45:00 · Ted 4.3% · guest 95.7%48:00 · Ted 20.7% · guest 79.3%48:00 · Ted 20.7% · guest 79.3%51:00 · Ted 100% · guest 0%51:00 · Ted 100% · guest 0%
Sharpest disagreement ▶ 21:00 Pushing back on market overreaction to unprofitable biotechs

Andy forcefully critiques irrational market pricing where 200 companies traded below balance-sheet cash as if their R&D pipelines possessed negative value.

Hardest push from Ted ▶ 18:42 Ted questioning sector-wide drawdowns vs idiosyncratic drug science

Ted challenges how broad sector market crashes occur if drug efficacy and commercialization are primarily idiosyncratic to individual molecules.

Biggest teaching moment ▶ 14:46 Explaining the Three Ps framework for commercial launches

Andy comprehensively details why 90% of Wall Street launch forecasts fail unless physicians, patients, and payers all share aligned economic and clinical incentives.

Ted holds their own ▶ 28:10 Ted examining management efficacy in science-driven industries

Ted demonstrates keen operational insight by questioning whether management quality is truly decisive when investment outcomes seem strictly dictated by underlying molecular biology.

the scores for every segment, with the reasoning behind each
ChapterTopicTed as informed peerGuest teachingGuest disagreementTed pushing backWhy
Andy Acker's Background and Path to Janus Henderson 2100 Ted opens with friendly biographical prompts acknowledging their shared business school background. Andy shares his personal journey from a family of doctors to biotech investing at Janus Henderson in an entirely collaborative tone.
A Quarter Century of Scientific Breakthroughs in Medicine 2600 Ted prompts Andy on the evolution of biotech science over his career. Andy delivers an educational overview comparing the 13-year Human Genome Project to modern sequencing, mRNA vaccines, antibody drug conjugates, and gene therapies.
The 90/90 Rule and the Three Ps Framework 3700 Andy introduces his core investment framework: the 90/90 rule (clinical trial failure rates and Wall Street consensus estimation error) alongside the Three Ps (physicians, patients, payers). Ted follows up with concise clarifying questions on the two sides of the rule.
Biotech Market Volatility and the 2021-2022 Bear Market 3610 Ted asks how idiosyncratic drug risk maps onto broad sector drawdowns. Andy details the historic 2021–2022 bear market, explaining how 200 companies ended up trading below cash and differentiating early development from early commercial firms.
Fundamental Research Process and Management Evaluation 3500 Ted probes how much management quality matters versus the underlying science. Andy shares a real-world case study of Global Blood Therapeutics, noting that underestimating management was one of the biggest lessons of his career.
Portfolio Construction, Sizing, and Trading Strategies 3500 Andy details his barbell portfolio structure, strictly capping binary risk to 100-200 basis points and rebalancing against intrinsic DCF valuations. Ted guides the technical discussion with questions on position sizing and behavioral trading.
Crossover Investing and High-Conviction Therapeutic Themes 2600 Andy explains the strategic advantage of private crossover investing (e.g., early BioNTech backing) and outlines major clinical frontiers in NASH, gene therapy, and incretin-based obesity treatments.
Industry Risks and Green Shoots in the Biotech Sector 2500 Andy analyzes policy risk from the Inflation Reduction Act and points to green shoots like corporate cash piles and M&A necessity as catalysts for a sector rebound before transitioning to lighthearted concluding questions.

Statements from this episode (17)

Opinion
Acker: Healthcare investors can have a bigger impact than practicing physicians
“I also felt that I could have a bigger impact as an investor than I could as a practicing physician. And then what's been really gratifying is that's turned out to be true.”
Andy Acker Oct 6, 2022 ▶ 2:47
Assertion Supported
Acker: Human Genome Sequencing Takes Hours for Hundreds of Dollars
“Now we can sequence a human genome literally in hours, and we can do it for hundreds of dollars.”
Andy Acker Oct 6, 2022 ▶ 5:55
Assertion Supported
Acker: US Drug Approvals Rose Over 100% Across Five Years
“In the last five years, there have been 256 new medicines approved in the United States, and that's up over a hundred percent from where we were just 10 years ago.”
Andy Acker Oct 6, 2022 ▶ 9:02
Prediction Not checkable as stated
Acker: Muscular dystrophy gene therapy could potentially launch by mid-2023
“There's been no disease-modifying therapy, and now we have a gene therapy that could be launching potentially by the middle of 2023.”
Andy Acker Oct 6, 2022 ▶ 9:47
Assertion Supported
Acker: 90% of drugs entering clinical trials never reach the market
“If you look at the industry over the last multiple decades, 90% of the products that begin human clinical testing never make it all the way to market.”
Andy Acker Oct 6, 2022 ▶ 10:45
Assertion Supported
Acker: The industry average success rate for Phase 3 trials is 50%
“And if you think about the industry statistics for a phase three study, the average success rate of the industry is about 50%.”
Andy Acker Oct 6, 2022 ▶ 11:51
Assertion Not checkable as stated
Acker: Wall Street drug launch estimates are wrong 90% of the time
“And what we've found again in more than 23 years of investing in health care is that the consensus estimates from Wall Street Are wrong about 90% of the time.”
Andy Acker Oct 6, 2022 ▶ 14:54
Assertion Supported
Acker: Physician prescriptions determine 80% of healthcare spending
“So the physicians write the prescriptions that affect 80% of healthcare spending.”
Andy Acker Oct 6, 2022 ▶ 16:34
Assertion Supported
Acker: Biotech experienced eleven bear markets of over 20% since 2006
“Back when the SMP select biotech index and the XBI, which is an ETF that tracks that broad biotech index that was created back in 2006. So about 16 years ago, since that time before the recent bear market, and we'll get to that, but there were 11 effectively b…”
Andy Acker Oct 6, 2022 ▶ 19:28
Assertion Supported
Acker: Biotech stocks fell 64% absolute and 75% relative in 2021-2022
“Between February of 2021 and June of 2022, we had one of the worst bear markets in biotech sector in history. So on an absolute basis, these stocks declined 64% and relative to the health care sector, they traded down about 75%.”
Andy Acker Oct 6, 2022 ▶ 21:45
Assertion Supported
Acker: Over 200 biotech companies traded below cash after the 2022 crash
“Now, after that, you get to a point where actually 200 different companies were trading below the levels of cash on their balance sheet. That's highly unusual. We've never seen that before, even going back to The global financial crisis and the bear market, th…”
Andy Acker Oct 6, 2022 ▶ 22:25
Insight
Acker: A bad management team can destroy a great drug molecule
“Probably the biggest mistake that I've made in my career is underappreciating how important a good management team is, because if you have a great molecule and it meets a bad management team, you can destroy a tremendous amount of value just by making bad deci…”
Andy Acker Oct 6, 2022 ▶ 28:40
Assertion Supported
Acker: Small and mid-cap biotechs develop over 60% of new medicines
“Over 60% of the new medicines that reach the market today were developed by small and mid cap biotech companies.”
Andy Acker Oct 6, 2022 ▶ 35:36
Disclosure
Acker: Janus Henderson invested in BioNTech in 2017 at $2B valuation
“BioNTech, which is the company that made the first MRNA vaccine along with Pfizer, we invest in that company when it was still a private company back in 2017 when most people had never heard of MRNA... Back then the company had a two billion market cap in 2021…”
Andy Acker Oct 6, 2022 ▶ 39:11
Assertion Partly supported
Acker: About a third of patients don't fill prescriptions due to co-pays
“Today, about a third of patients don't fill their prescriptions because of the co-pays that they can't afford”
Andy Acker Oct 6, 2022 ▶ 44:25
Assertion Supported
Acker: Pfizer needs to acquire $25 billion in revenue by 2030
“And even just Pfizer alone has said that they need to make acquisitions to acquire twenty five billion dollars of revenue by the end of 2030.”
Andy Acker Oct 6, 2022 ▶ 47:40
Insight
Acker: Buy hated biotech companies after trial setbacks if the drug works
“So it's really buying when a company is the most controversial, the most hated, but where you have high conviction that a product really works.”
Andy Acker Oct 6, 2022 ▶ 50:10
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