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Colossus (Invest Like the Best / Business Breakdowns)Podcast15 Jun 2025Source: joincolossus.comHost: Patrick O'Shaughnessy

Dinakar Singh - A Father’s Call To Action - [Invest Like the Best, EP.428]

In plain words

A hedge fund manager, Dinakar Singh, spent $150 million of his own money to develop three drugs for his daughter's rare disease (spinal muscular atrophy) after his diagnosis. He used a 'parallel processing' approach (trying all paths at once) instead of the usual slow, step-by-step method. He regrets not capping prices—now some drugs cost $730,000 a year. Key players: Biogen (its SMA drug makes $4-5 billion yearly but is criticized for high cost), Novartis (bought a gene therapy for $8.7 billion, but only works for very young kids), and Roche (his daughter uses their daily injectable pill).

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This episode of Invest Like the Best features a conversation with Dinakar Singh, founder and CEO of Axon (formerly TPG-Axon Global Long/Short Hedge Fund). After his son was diagnosed with spinal muscular atrophy (SMA), Singh combined his financial background with pharmaceutical R&D, using a "virtual

~9 min full read · 8 sections
Deep Analysis

Dinakar Singh - A Father's Call To Action - [Invest Like the Best, EP.428]

At a Glance

Dinakar Singh, former founder and CEO of TPG-Axon hedge fund, combined his financial background with drug development after his daughter was diagnosed with spinal muscular atrophy (SMA). He drove the approval of three SMA treatments through a "virtual company" model. Singh argues that in biotech investing, time is the scarcest capital, and "parallel processing" rather than "sequential advancement" is key to breaking the deadlock of rare disease drug development — he self-funded approximately $150 million, compressing a development cycle that might have taken decades into the fastest approval timeline in FDA history.


From Diagnosis to Determination: When the "Worst Outcome" Becomes the Trigger for Action

Singh believes that for parents, "seeing their child suffer while realizing they could have done something but didn't act in time" is more terrifying than losing the child—this fear drives him to act "at maximum speed and with no effort spared."

  • Diagnosis Background: In 2001, his 15-month-old daughter was diagnosed with SMA—then known as "the deadliest childhood genetic disease," affecting approximately 20,000 children each year. The doctor gave only a 60-second phone call because at the time "no one knew what SMA was."
  • Time Window: His daughter's case was of moderate severity, with a projected life expectancy of 10–15 years, but with progressive muscle weakening. Singh concluded: "If we waited for decades, she would be gone by then."
  • Key Insight: SMA patients have a "backup gene" (SMN2), but it is defective—this means the challenge is not about "creating something from nothing" with gene replacement, but rather "repairing an existing factory," making it far less difficult than traditional gene therapy. Moreover, the SMA protein has an "extremely wide therapeutic window" (overdosing is nearly impossible), which reduces the core risk of drug development.
  • Logic of Action: Singh directly applies the concept of "time value" from investing—every day of success earlier gives his daughter a greater chance of survival. He left Goldman Sachs and founded TPG-Axon, with the core motivation being "to earn enough money as quickly as possible, then pour everything into R&D."

Virtual Company Model: Reconstructing Drug Development with Financial Thinking

Singh explains that traditional drug development is "serial"—do one study, then decide the next step, taking over a decade. He advocates for "parallel" processing: advancing five paths simultaneously, exposing failures quickly and accelerating successes.

  • Resource Investment: Approximately $150 million of his own funds, all used for R&D, not company operations. Singh says, "My father jokes that I've developed the most expensive drug habit in the world."
  • Talent Network: Gathered 15–18 top global drug development experts, forming a "volunteer think tank"—these people accept no salary, come for a few weekend brainstorming sessions each year. Singh emphasizes: "They are willing to invest because this is a person who truly has a chance to solve neuroscience problems—and neuroscience is the 'graveyard' of drug development."
  • Open Testing Platform: Singh's team built their own mouse models and cell models, opening them free of charge to global pharmaceutical companies—companies only need to send their compound libraries, testing is free, IP belongs to the company, only asking "if you discover something, please tell us." Even so, it took years to persuade Novartis to participate.
  • FDA Advocacy: Singh facilitated a joint letter from 50 Nobel laureates, placed a full-page ad in a Washington political newspaper, and persuaded the FDA to accept "natural history studies" as a control group—meaning clinical trials would not need half the children to take a placebo (otherwise many children would die in the trial). This made the SMA drug one of the fastest-approved drugs in FDA history.

Three Paths, All Successful: Luck or Systematic Design?

Singh attributes his success to "luck," but a more accurate description is that by systematically covering all possible mechanisms, he increased the probability of "winning the lottery."

Drug Type Main Driver Key Milestone Current Status
Antisense Oligonucleotide (ASO) Ionis → Biogen First to be approved, fastest FDA review Annual fee ~$730,000; now one of Biogen's three top-selling drugs, annual revenue ~$4-5 billion
Small Molecule PTC Therapeutics → Roche Drug used by his daughter Daily injection, effective and safe
Gene Therapy Avexis → Novartis (acquired for $8.7 billion) First approved gene therapy drug Only suitable for very young children (viral vector toxicity is too high for older children)
  • Singh's reflection: "We selfishly focused only on what we needed most (the small molecule), but we made sure all three paths had someone working on them—because gene therapy only works for very young children, and our daughter was already 12 years old."
  • Investment logic analogy: This is not "diversified betting," but "covering all factors that could yield success"—in a portfolio, this means positioning should cover all mechanisms that could generate returns, rather than betting on a single path.

Ecological Evolution and Cost Dilemma: From "Nobody Wants It" to "Nobody Can Afford It"

Singh points out that the success of the SMA drug market has changed the narrative of rare disease R&D—but extreme pricing and international regulatory fragmentation are creating new tragedies.

  • Before and After: 20 years ago, Singh took a business plan pricing $5,000-$15,000/year to lobby big pharma, and they scoffed: "The most expensive drug is only $50,000/year, no one will pay that much for a pediatric rare disease." Today, SMA drugs are priced as high as $730,000-$2 million/year, and the entire SMA drug market is approaching $10 billion.
  • Singh's regret: "I wish that when we invested, we had included a price cap clause—million-dollar pricing is insane."
  • New problem: There are still children who cannot access treatment due to international regulatory barriers and pricing issues. Singh gives an example: a family from Uzbekistan raised $400,000 through crowdfunding, but could not receive treatment in the US or UK because "the regulatory framework between countries is completely chaotic."
  • Future direction: Singh is pushing for "muscle regeneration" drugs—these drugs are not only effective for SMA but may also be applicable to a broader range of muscle wasting diseases (such as ALS, elderly muscle weakness). "SMA is becoming a 'model disease' for muscle research—because the holes in the boat have been patched, and now we can really drain the water."

Mentioned Positions

Position Guest Attitude Key Data
Biogen Neutral (mentions collaboration) Its SMA drug costs approximately $730,000 per year, with annual revenue of about $4–5 billion
Novartis Neutral (mentions collaboration and acquisition) Acquired Avexis gene therapy for $8.7 billion; early on, it offered free testing of compound libraries
Roche Neutral (mentions collaboration and that his daughter is using its drug) The drug is a daily injectable small molecule; Singh's father previously worked at Roche
Ionis Pharmaceuticals Neutral (partner) Developed the first approved ASO drug
Avexis Neutral (acquired entity) Developed the first approved gene therapy drug
PTC Therapeutics Neutral (R&D partner) Identified an effective small molecule drug through extensive screening
Jackson Laboratory Positive (Singh currently serves on the board of directors) Core supplier of mouse models; Singh plans to establish a "Rare Disease Think Tank" there

Judgments Worth Remembering

1. “The worst thing is not that the child suffers, but that you realize you could have done something but didn’t have time.” — Singh used this “personal risk formula” to define action priorities: time is scarcer than money, and parallel execution is safer than serial.

2. “Neuroscience is a graveyard for drug development—but SMA has a ‘backup gene’ and an extremely wide therapeutic window, which makes it more ‘solvable’ than most neurological diseases.” — This shows that sound investment judgment requires identifying problems that are “structurally easier to solve,” rather than focusing only on scale.

3. “We open up all testing resources, and the company retains the IP—we only ask that someone discovers something and tells us.” — This is a “platform” approach to R&D: giving up ownership in exchange for information flow, reducing the cost of trial and error for all participants.

4. “If you had told me 20 years ago that SMA drugs would sell for a million dollars a year, I would have thought you were crazy—now it’s reality, and I regret not adding a price cap when I invested in the beginning.” — Singh candidly reveals the “narrative reversal” of rare disease drug pricing: from no one caring to no one being able to afford it, the system needs new constraints.

5. “SMA is becoming the ‘standard model’ for muscle research—because the hole in the boat is patched, and now we can really drain the water.” — This means that a breakthrough in the “infrastructure” of a field (such as an effective base treatment) can unleash downstream innovation potential, and investors should focus on the second wave of opportunities after “patching the hole.”

6. “Gene therapy can only save very young children—for older people, the viral vector itself will kill you.” — This is a critical technical time window constraint: not all therapies are applicable to all patients, and investing requires a precise understanding of the technology’s applicable boundaries.

7. “My ‘Ghostbusters’ plan: set up a team at Jackson Lab to help rare disease families create a ‘game plan’—no fees, no IP ownership, just be the ‘Switzerland.’” — Singh attempts to replicate the “model” from SMA’s success (parallel execution, neutral coordination, open resources) to other rare disease areas, with the goal of lowering the entry barrier for the “first attempt.”