FIBROGEN INC earnings calls

How roxadustat dose changes are decided

Q (Alex Ramsey · William Blair): How is the decision made to titrate roxadustat up to 3.5 mg/kg? Is it based on tolerability or efficacy, and what is the timing and interval for assessments?

A: Management said dose changes are based on an assessment of benefit and risk. They said a change in dose is possible every six weeks. They also said sites will get specific guidance based on hemoglobin level and the rate of rise.

Are there dose steps between 2.5 and 3.5 mg/kg?

Q (Carol Gaddum · William Blair): If a patient goes up from 2.5 mg/kg, is it straight to 3.5, or are there intermediate dosing steps and timing details?

A: Management said there are intermediate dose steps between 2.5 and 3.5 mg/kg. They reiterated dose changes can occur every six weeks based on benefit-risk assessment. They also said sites will have specific guidance tied to hemoglobin level and the rate of rise.

"Alex, there will be very specific guidance to the sites on the titration either up or down based upon a number of factors including hemoglobin level and the rate of rise of that hemoglobin level as well." — Thane Wettig (CEO)

Phase III start: partner or internal? MATTERHORN impact

Q (Matthew Keller · H.C. Wainwright): Will you start phase III only with a partner or can you do it internally? Did the MATTERHORN data change partnering plans or the phase III design?

A: They are running parallel paths: they may develop internally but would need to bring in capital, and they are also evaluating strategic partners. From a clear economic point, if Kyntra develops and commercializes on its own it would owe AstraZeneca a mid-single-digit royalty on net sales; if Kyntra partners, AstraZeneca would get 35% of any economics to Kyntra. They said MATTERHORN informed the phase III design, isolating transfusion burden as a key variable and ensuring enrollment of both RS+ and RS- patients.

"When we negotiated those rights back from AstraZeneca, if we were to develop roxadustat on our own and commercialize on our own, we would owe AstraZeneca a mid-single-digit royalty on net sales." — Thane Wettig (CEO)

Prior Pluvicto patients, biopsies, and ctDNA

Q (Michael King · Rodman & Renshaw,): How many enrolled patients have prior Lutetium-177 (Pluvicto) treatment and can you enrich for them? Also, will you collect pre/post biopsies and use ctDNA?

A: They said prior Pluvicto-treated patients are allowed in the trial and about 30% of randomized patients so far were previously treated with Pluvicto, and they have a pre-specified analysis in the SAP by prior Pluvicto exposure. They are collecting tissue, PSMA scans, PET scans, and FG-3180 scans as much as possible but noted limits due to patient burden and tissue availability. They will look at ctDNA and noted the phase I monotherapy trial showed a nice ctDNA effect with FG-3246.

"To your point, we clearly are allowing prior Pluvicto-treated patients into the trial." — Thane Wettig (CEO)

Positioning FG-3246 and moving roxadustat earlier

Q (Jay Olson · Oppenheimer): Do you see FG-3246 as best for PSMA-low or negative patients, or complementary to PSMA therapies? And how might roxadustat move into first-line settings?

A: They said the phase II is designed to answer those questions and they are allowing prior Lutetium-177 patients to see how responses differ across subgroups. They are doing scans to understand where the greatest unmet need and value proposition for FG-3180 is, and lifecycle moves would typically be post-chemo to pre-chemo to hormone-sensitive; strategy will be data-driven. Clinicians told them after PSMA-directed RLT, they often look to a different target and modality, such as an ADC targeting CD46 rather than another PSMA-directed therapy.

"I think these are exactly the type of questions we're looking to address with the phase II, and that's why we're allowing prior Lutetium-177 to understand how responses are similar or different in different patient subpopulations." — Carol Gaddum