Why phage companies aren’t raising $400M rounds… yet | Paul Garofolo Podcast Episode · Podovirus · April 21 · 1h 2m

6/ Listen to the full episode:

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5/ His advice for phage researchers: work on payloads, chase government funding, and don't sleep on the microbiome.

"I don't think you have a safer delivery vector to get something into the human body that's better than phage."

4/ Paul thinks intracellular pathogens are the holy grail.

If phage can clear bacteria hiding inside cells — where antibiotics fail — "we have a new field of medicine."

Think Crohn's, chronic UTIs, and beyond.

3/ They’re now on patient 188 of 288 in what may be the largest phage clinical trial ever.

94% of bacterial isolates stay sensitive to their phage cocktail — a rate that’s held from lab screens through to the clinic.

2/ Locus Bio started as a CRISPR-Cas3 company.

They tested 3 delivery vectors — nanotech, cell-penetrating peptides, and phage.

Phage won because it carries huge payloads AND can't infect human cells.

That safety profile is unmatched.

1/ "Why can't phage companies attract $400M rounds?"

Locus Bio CEO Paul Garofolo thinks the answer is uncomfortable: too many small, underpowered trials producing mediocre data have cooled investor confidence across the whole field.

Why? And how do we fix it?

Chip Schooley & Graham Hatfull: the state of phage therapy (& what HIV can teach us) Podcast Episode · Podovirus · April 3 · 1h 7m

5/ Find out all the answers on our newest Podovirus podcast episode with the legendary Chip Schooley & Graham Hatfull 👇

🎥 YouTube: youtu.be/lm3LdG8iEDY
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4/ Many lessons. For one: every phage trial should be designed so we learn something even when it fails.

Chip calls it “principles of phage therapy” vs “anecdotes and adventurism.”

Which one better describes the phage therapy field right now?

3/ Last October, Graham & Chip built the conference they felt was missing — academic, peer-reviewed, spanning phage biology through to the clinic.

250+ scientists and clinicians in Washington, D.C. What came out of it?

2/ Graham Hatfull has led collection of ~30,000 phages (phagesdb.org), and thinks natural phages are just the starting point.

The future is synthetic — designed killing machines. But what do we need to learn from natural phages first?

1/ Chip Schooley (cofounder of UCSD's IPATH) was there when HIV went from “some people benefit” to functionally cured.

His take: phage therapy is at about 1988 on that timeline.

How do we get it into the 90s?

Excited to see @dariavantyne.bsky.social and Van Tyne Lab featured on the Podovirus Podcast!

Great conversation on how translational phage work actually gets done. 🧫

Check out the links below for the full story! #pittsburghphageprogram #p3 #phages #infectiousdiseases #phagetherapy

How to run a phage therapy center from your academic lab In this episode, Joe and I sat down with Dr. Daria Van Tyne, PhD, Associate Professor of Medicine at the University of Pittsburgh and researcher in the Divis...

Check out our conversation with Daria on the Podovirus podcast!

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10/

Where does she hope the field is in 15 years?

FDA-approved phage products, and compassionate use still running alongside them.

“There will always be patients who don’t fit trials. The two will coexist.”

9/

Her research questions now come straight from the clinic:

Does resistance evolve during treatment? How often? In what way?

Can phage clear biofilms?

What actually happens to the microbiome?

8/

On the FDA: she used to dread Friday emergency calls that felt like her PhD qualifying exam.

Now it's mostly email. 30-day windows. A program manager handling paperwork. It's routine.

“They’ve evolved as the field has evolved.”

7/

One step she won’t delegate: formulation.

Once a week, 8:30–9am — after preschool drop-off, before her students arrive — she’s alone in the lab formulating IV phage.

“I want to be the one to own it.”

6/

On manufacturing, she’s optimized everything she can.

Weekly batching for susceptibility testing.

Pre-made cocktail vials in the fridge.

Multi-patient preps.

Low-bind tubes to keep phage titers stable for 6+ months.

5/

Collaboration in the phage therapy community is the theme Daria returns to often.

“I’ve gotten as far as I have because of the generosity of this community.”

Her biggest fear? VC money enters, greed/ego ensues, and people stop sharing phages for patients.

4/

Her first case (2020): a CF patient post–lung transplant w/ a decade-long Burkholderia infection.

None of her phages matched. She called Ben Chan @Yale. He worked overnight & had a phage within 1 wk.

This quick + helpful collaboration launched her phage therapy operation..

3/

First, you have to build your phage library right.

Daria's team only uses the scariest bugs as bait.

They collects drug resistant clinical isolates from physician colleagues & fish for phages in hospital wastewater.

If a phage kills those bugs, it's clinically relevant.

2/

In 2018, @dariavantyne.bsky.social started her phage lab at @pittdeptofmed.bsky.social.

She had 0 phages, just knew their biology & wanted to help patients.

Today her lab makes phage for dozens of patients/year under compassionate use, while still publishing research.

We asked Daria: HOW?

🧵1/

Oh also find John Rex here! @johnhrexmd.bsky.social

Plazomicin (Achaogen) financial post-mortem: #PassPASTEUR Dear All (and with thanks to Kevin for co-authoring and also a wonkish alert … get your coffee and settle in for the details), If you’ve been around the antibiotic ecosystem for a while, you’ve hopefully heard the story of the 2019 bankruptcy of Achaogen and the subsequent loss to the entire world of its […]

6/ The solution? We need new models that pay for ACCESS, not USAGE

Think Netflix subscription > pay per view

Read the full analysis by @JohnRex_NewAbx: amr.solutions/2024/10/14/plazomicin-ac...

/end

5/ Why this matters for scientists:

We're not just losing drugs. We're losing the teams who know how to make them.

Talent is leaving the field. (The true cost of broken incentives)

4/ The hidden tragedy: Plazomicin still WORKS. It could save lives.

But without a company behind it = limited global access

Like having a fire extinguisher no one can buy 🧯

3/ The painful numbers from @JohnRex_NewAbx's analysis:
- $500-600M to reach approval
- +$350M to keep it on market 10yrs
- Expected sales? Minimal

Because good stewardship = less use = bankruptcy 🤯

2/ The developer's paradox: "Make something AMAZING... that we hope rarely gets used"

Investors: "So we spend millions to create a drug that sits on a shelf?"
Scientists: "Yes! That's the point!"
Investors: *leaves chat*

1/ The Achaogen story haunts scientists:
- Spent 9 years developing plazomicin
- Got FDA approval in 2018
- Raised $776M (!!)
- Bankrupt by 2019
- Sold for pennies: $16M

The math wasn't mathing 📉

🧬 Big Pharma's antibiotic problem:
A successful drug + FDA approval = $776M loss

Here's how that happens 🧵