How the ADPKD maps started

It all started right before BIO…

I was looking for people to meet on the conference platform when a "Renal" tag caught my eye. With one click, I could see pharmas, biotechs, investors, patient associations and CROs with any interest in renal indications.

We had just nominated ADPKD (Autosomal Dominant Polycystic Kidney Disease) as our lead indication then, positioning it to spearhead our pipeline of RNA-upregulating small molecules. We did not take that decision lightly (oh, so not lightly!), but I knew I still had so much to learn about the disease and its therapeutic landscape. Mapping the programs in development seemed like a good place to start.

Figure 1: An ADPKD market map. 46 active programs from companies and academic groups, one chip per program, in rows by modality (mRNA-upregulating small molecules and ASOs, PKD protein correctors, signaling modulators, read-through correctors, gene therapy, gene editing, antibodies, undisclosed, repurposing) and columns by stage, from preclinical to approved (Otsuka's tolvaptan). — Figure 1. It started with an ADPKD market map. Explore it in the active programs map

At the conference, people got excited when I mentioned the map I made, so I started sending it around. People started telling me about programs I'd missed. A random search led me to PKDCureTracker.com by Renato Molina Toth, which revealed many repurposing programs. And my weekly ADPKD alert kept surfacing news of even more programs.

A mental model started to form: Otsuka Pharmaceutical bringing first hope and validating the market; Vertex Pharmaceuticals, AbbVie / Calico Life Sciences and Novartis (acq. Regulus) bringing additional modalities to the clinic; researchers from around the globe spinning out their discoveries - xCystence Bio (AUS), Nephrogen (SF), Borealis Biosciences (CAN), Mezzion (KOR); and visionaries like Torque Bio, Estuary Biotherapeutics, Renasant Bio and many more who are pushing the boundaries of science to promote human health.

Then I got curious about discontinued programs: why were they stopped? what's been learned? how did the field evolve?

Figure 2: The same pipeline grid with the history added: 77 programs, 46 active and 31 discontinued, the discontinued ones shown faded in the stage they reached. — Figure 2. What about all the history? Explore it in the history map

Figure 3: A timeline from 2000 to today, one line per program from its first public evidence to today or to its last news. Active programs run in green to today; discontinued ones are colored by why they stopped: efficacy, safety, strategic or not disclosed. — Figure 3. How does it fit into a timeline? Explore it in the history map (timeline view)

This became a little obsession, and here's what I learned:

⤵️ Many programs targeting indirect pathways were discontinued for lack of efficacy.
🏦 Some were neglected simply because their parent company was acquired for a lead program outside PKD.
📈 That latter pattern is fading. More companies now have ADPKD as their lead indication, and interest in the space is growing.

But on paper it was still one huge table, and that's not how I think. My brain visualizes networks and relationships. So I asked Claude to help me turn everything into a cell model. It took a few iterations, I'll tell you, but I love the result. It teaches me things the raw tables never showed me.

Figure 4: A cyst-lining kidney cell with the disease pathway drawn in: the PC1 route from gene to primary cilium, cAMP, mTORC1, AMPK and other steps, each marked as overactive or reduced in ADPKD. Every program sits on the step it targets, circles for active and squares for discontinued, colored by modality; whole-kidney drugs and undisclosed mechanisms sit beside the cell. — Figure 4. How does it fit into a cell? Explore it in the cell map

Since the work was already done (OK, Claude did most of it, but I told it what to do!), I thought it would be nice to share it with the community 🤗
Thank you to everyone working on this worthy cause. I hope we can help bring patients the cure they've waited far too long for ❤️

Figure 5: What is the broader ecosystem? The people and organizations around these programs: pharma, researchers, investors and foundations, coming next in this series. — Figure 5. The broader ecosystem, coming next in this series. First up: Who invests in ADPKD

Sources

Programs, active and discontinued: the Renasis Bio active programs map, history map and cell map, each program linked to its sources; as CSV: programs.csv, organizations.csv, program_owners.csv
Repurposing programs: PKDCureTracker.com