Why phage companies aren’t raising $400M rounds… yet | Paul Garofolo

Why phage companies aren’t raising $400M rounds… yet | Paul Garofolo

“The thing everybody thinks is a tailwind for our space — the low financial barrier to get into a clinical trial — is actually one of the largest headwinds.” Paul has spent 35 years in biopharma, and he has a sharp take on why phage therapy isn't pulling in the same kind of investment as other biotech sectors. Cheap, small trials have produced mediocre data that's spooked the money — and the field is paying for it. In this episode, Paul walks us through what it actually takes to get phage drugs through the clinic, why his company believes intracellular pathogens are the next frontier, and how Locus went from a CRISPR-Cas3 startup to dosing patient 188 of 288 in what may be the largest phage clinical trial ever. In this episode: * How Locus tested CRISPR-Cas3 delivery via phage, nanotech, and cell-penetrating peptides — and why phage won * The EpiBiome acquisition and the $800M Janssen partnership * Why Phase 0 trials are worth the investment * The problem with low-cost, underpowered clinical trials damaging the field’s reputation * Getting PKPD right before progressing — “the right drug at the wrong dose still fails” * Why intracellular pathogens could unlock phage therapy as a new field of medicine * The 5-year plan (engineered cocktails for MDR infections) and 15-year vision (anti-inflammatory, oncology, neurology) * Advice for researchers: work on payloads, chase government funding, and don’t give up on the microbiome Guest: Paul Garofolo, CEO of Locus Biosciences (@locusbio) Hosts: Jessica Sacher & Joe Campbell Learn more: https://www.locus-bio.com/

Chip Schooley & Graham Hatfull: the state of phage therapy (& what HIV can teach us)

Chip Schooley (UC San Diego, IPATH) and Graham Hatfull (University of Pittsburgh) join us to discuss why phage therapy needs biologists and clinicians collaborating — and what the HIV field’s playbook can teach us. Topics covered: • Why they organized an academic phage conference in Washington, D.C. • The state of in vitro phage assays and the reproducibility problem • How to design phage clinical trials that actually teach us something • Phage resistance, fitness trade-offs, and the role of the immune system • What HIV’s journey from 1988 to 1998 tells us about where phage therapy is headed • Why synthetic biology is the future of phage therapeutics • The need for young scientists entering the field Guests: Chip Schooley — Co-founder, IPATH Phage Therapy Center, UC San Diego. Physician behind the Tom Patterson case. HIV research veteran. Graham Hatfull — University of Pittsburgh. Runs the world’s largest phage collection. Creator of SEA-PHAGES. Hosts: Jessica Sacher & Joe Campbell Links: IAS-USA: The conference Chip & Graham describe in the episode was sponsored by the International Antiviral Society-USA (Executive Director: Donna Jacobsen): https://www.iasusa.org/

How to run a phage therapy center from your academic lab

What does it take to build a phage therapy program from nothing — and keep your research lab running at the same time? 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 Division of Infectious Diseases at UPMC. When Daria arrived at Pitt in 2018, she describes herself as "phage poor" — a lot of interest in phages, zero phages in hand. Today, her lab manufactures phage for dozens of compassionate use patients per year, all while continuing to publish research. Daria's commitment to owning the process end to end is especially fascinating to hear about — right down to personally doing the phage formulation herself every morning after preschool drop-off, because, as she put it: "if I'm making something that's going to be administered intravenously to patients, I want to be the one to own it." 🔬 Highlights: Building a phage library from scratch: How Daria used multidrug-resistant clinical isolates as bait to fish phages out of hospital and municipal wastewater — ensuring clinical relevance from day one. The first cases: From a cystic fibrosis patient post-lung transplant with Burkholderia multivorans in 2020, to partnering with Ben Chan at Yale and Breck Duerkop at Colorado when they didn't have the right phages in-house. Making manufacturing sustainable: Only using phages so good undergrad students can make them grow reliably, batching workflows, pre-manufactured cocktails, protein low-bind tubes, and more. QC that works for her lab and the FDA: Whole genome sequencing for identity and purity, cesium chloride banding, endotoxin testing, USP-71 sterility. Working with the FDA: From nerve-wracking Friday evening conference calls for emergency INDs to the much calmer world of single-patient INDs and email correspondence — and why she sees the FDA as a partner, not a gatekeeper. The phage susceptibility testing problem: Why the field still lacks standardized, clinically translatable assays, and what it would take to make phage susceptibility testing work in a real clinical microbiology lab. Research questions that keep her up at night: Phage resistance evolution in patients, whether phages can clear biofilm infections, and what phage therapy actually does to the microbiome. The future she's hoping for: FDA-approved phage products, with compassionate use and clinical trials coexisting for the long tail of complex cases — and her biggest fear being that investor money kills the collaborative spirit that has made the field work. 📺 Watch on YouTube: https://youtu.be/nbN4whcoJrU 🔗 Learn more: Pittsburgh Phage Program (P3): https://dom.pitt.edu/id/research/phage/

AI-generated phages that work: ChatGPT for phage biologists?

Can AI design living organisms from scratch? Samuel King and Claudia Driscoll from the Arc Institute used genome language models to generate functional phages—and 16 of them actually worked in the lab. Not only that, they killed bacteria equally or better than the natural phage the team used as a template.  In this episode, we dig into how they did it, what it means for phage research, and why this could be a new way to explore evolution and design genomes. What we covered: • How genome language models work (ChatGPT, but for DNA) • Training on millions of phage genomes with Evo-1 and Evo-2  • The creativity (from biologists!) required to figure out how best to filter generated sequences • Going from 4000 selected sequences in silico, to 300+ synthesized candidates, to 16 working phages • Fresh phage lab protocols for new ways to look at phage fitness • Phage "personalities" that emerged from the generated candidates • Watching recombination occur among a cocktail of designed phages • Cost realities: hundreds of dollars per 5kb genome candidate, but emerging ways to reduce it exist! • Good news: All tools are open source and free to use! The preprint: Samuel H. King, Claudia L. Driscoll, David B. Li, Daniel Guo, Aditi T. Merchant, Garyk Brixi, Max E. Wilkinson, Brian L. Hie (2025-09-17). Generative design of novel bacteriophages with genome language models | bioRxiv. biorxiv.org. Retrieved November 8, 2025, from https://www.biorxiv.org/content/10.1101/2025.09.12.675911v1 More resources: • Arc Institute Evo browser interface: https://arcinstitute.org/tools/evo • GitHub (open source code): Evo2: https://github.com/ArcInstitute/evo2)  • Hugging Face (model downloads): https://huggingface.co/arcinstitute Guests: Samuel King: PhD candidate, Stanford/Arc Institute, Brian Hie's lab; follow @samuelhking on X Claudia Driscoll: Postdoc, Arc Institute, Brian Hie's lab, follow @driscoll_cl on X Also follow @BrianHie, @arcinstitute, @stanford on X for more from this team!

How to get successful outcomes with phage therapy: Saima Aslam, MD, MS

"When I first started, I was treating anything and everything in terms of ‘this is highly drug resistant and it's failed’. But I think I have a clearer idea now, at least clinically, where I think phage would be beneficial, rather than all comers.” What does it take to achieve an 85% success rate with phage therapy? We talk to Dr. Saima Aslam, MD, MS, a Professor of Medicine at UC San Diego and the clinical lead of IPATH (Center for Innovative Phage Applications and Therapeutics), about her strategies for successful phage treatment.  Since 2017, Dr. Aslam has treated many patients with phages, and learned crucial lessons about patient selection, trial design, and the importance of collaboration between clinicians and phage researchers. We explore how her approach has evolved from "treating anything and everything" to targeted strategies, why early clinical trials struggled, and her exciting NIH-funded placebo-controlled trial for recurrent UTIs in kidney transplant patients.  The conversation covers practical implementation challenges and lessons for phage therapy practitioners, and discusses her vision for a centralized US phage repository and manufacturing center to reduce the current 6-12 month delays in accessing treatment. Here's a taste of what we covered: 1. 🧫 Why patient selection is crucial: not all infections benefit equally from phage therapy 2. 🏥 Why phage scientists and clinicians must work together from day one 3. 🧪 Learning from early studies to create pragmatic, enrollable protocols 4. ⌛ The challenge of long-established biofilms in chronic infections like LVAD bacteremia 5. 💉 Why recurrent UTIs in transplant patients represent the "lowest hanging fruit" 6. 🔬 How Dr. Aslam designed her NIH-funded clinical trial for recurrent UTIs in kidney transplant patients 7. 🌐 The urgent need for centralized phage production in the US to reduce treatment delays Chapters: 00:00 Introduction to Phage Therapy and Dr. Saima Aslam 02:11 Early Experiences and Lessons in Phage Therapy 05:27 Criteria for Patient Selection in Phage Therapy 09:14 Challenges in Phage Therapy: Availability and Effectiveness 12:31 Collaboration and Research in Phage Therapy 24:08 Bottlenecks in Phage Therapy Development 36:07 Future Directions and Hopes for Phage Therapy Learn more: Saima’s team is now enrolling for their kidney transplant phage clinical trial! (https://clinicaltrials.gov/study/NCT06409819) A recent paper by Saima and her team: Phage Therapy in Lung Transplantation: Current Status and Future Possibilities (https://pubmed.ncbi.nlm.nih.gov/37932113/)