66 companies are segmented by radioisotope and highest stage of development

Further thoughts on this emerging market below:

What was once a dormant space has seen rapid growth over the past few years

Since 2018:

• 3 novel FDA-approved therapeutics
• >$1B in investor funding
• >$10B in M&A and licensing deals

With the current industry pipeline showing >60 clinical-stage and >100 preclinical assets

Radiopharmaceuticals are radioactive drugs for imaging or therapeutic use

They can be delivered as individual elements or via targeting components such as small molecules, antibodies or peptides

Isotope use varies from canonical (177-Lu, 131-I) to emerging (225-Ac, 90-Yt)

While agents such as Iodine-131 have been in use since the 1940s, the "1st gen" assets were released in the early 2000s, namely Zevalin (IDEC Pharma / Biogen, 2002) and Bexxar (GSK, 2003)

These early drugs failed commercially due to a confluence of factors:

(1) Dosing required specialist radiation oncologists & facilities whereas SoC (rituximab) did not

(2) Short half-life & reliance on centralized manufacturing meant an overly tight timeframe to ship, deliver & dose patients

These two factors killed use in the community setting

(3) Less favorable reimbursement structure for a more logistically-intensive treatment

(4) Concerns around radioactive toxicity and a lack of long-term safety data

(5) Shortage of trained nuclear medicine physicians (The US only produces ~100 / year)

So what triggered the current Renaissance in the space for 2nd Gen?

• Focus on indications with limited treatment options (i.e. NETs)
• Cell therapy uptick has "elevated" ability to handle complex logistics
• Consolidation of medical & radiation oncology practices

Lutathera (Novartis) was a big leap forward for the space, as it proved a bespoke radiopharmaceutical could effectively target solid tumors - including difficult-to-treat indications

And combinations with immunotherapies, chemo or other modalities should further improve responses

There's also been improvement in the core differentiators of the class:

• Difficult for tumors to develop resistance mechanisms due to double-strand breaks
• No boxed warnings
• Precise dosing as the drug can be tracked in the patient, minimizing off-target effects
• A difficult supply chain cuts both ways and acts as a moat for incumbents
• Theoretically more robust vs. biosimilars
• Preferential status under IRA as Medicare Part B drugs (price negotiations delayed 2 additional years to 2028)
• Alpha emitters can be dosed out-patient