Press Release: Basilea provides updates on efficacy data with derazantinib in bile duct cancer and on ongoing clinical programs in urothelial and gastric cancer

-- An updated analysis shows further improvement of progression-free

survival, disease control rate and objective response rate in the cohort

of FGFR2 gene fusion-positive patients with bile duct cancer (iCCA) in

FIDES-01 study

-- Pursuing intensified dose regimen in FIDES-02 urothelial cancer study and

FIDES-03 gastric cancer study

Basel, Switzerland, May 31, 2021

Basilea Pharmaceutica Ltd. (SIX: BSLN) today reported updated response

data from cohort 1 of the FIDES-01 study. The cohort is assessing the

anti-tumor efficacy of the orally administered fibroblast growth factor

receptor (FGFR) inhibitor, derazantinib, in patients with FGFR2 gene

fusion-positive intrahepatic cholangiocarcinoma (iCCA), a form of bile

duct cancer.(1) The positive efficacy data further substantiate the

clinical proof-of-concept of derazantinib as monotherapy in iCCA.

FIDES-01: ICCA

Topline results for cohort 1 of the FIDES-01 study were presented in

early February 2021.(2) An updated analysis based on a data cut-off in

April 2021 has now been completed and shows that the objective response

rate (ORR) increased from 20.4% to 21.4%, the disease control rate (DCR)

from 72.8% to 74.8% and the median progression-free survival (PFS) from

6.6 to 7.8 months, further supporting the clinically relevant efficacy

for derazantinib monotherapy in this indication.

Dr. Marc Engelhardt, Chief Medical Officer, said: "We are very pleased

with the more mature results from the first fully enrolled patient

cohort of the FIDES-01 study. The progression-free survival of 7.8

months is in the upper range reported for this endpoint with

FGFR-inhibitors in this patient population. Derazantinib also continues

to show a well-manageable safety profile, with low rates of retinal side

effects, stomatitis, hand-foot syndrome and nail toxicity. Overall,

these results underscore the favorable benefit to risk profile of

derazantinib as a monotherapy in bile duct cancer."

He added: "We are also making good progress in cohort 2 of the study,

which is enrolling iCCA patients with FGFR2 gene mutations or

amplifications. We have achieved about 50% of target enrolment and are

aiming to report topline results in the first half of 2022. If the

encouraging results from the recently reported interim results are

confirmed upon completion of the study, this will further strengthen the

evidence of a differentiated efficacy and safety profile for

derazantinib in bile duct cancer."

FIDES-02: Urothelial cancer

Basilea had decided to explore an intensified dose regimen in several

cohorts with derazantinib monotherapy and combination therapy in the

FIDES-02 study in patients with urothelial cancer.(3) Based on interim

efficacy data from the ongoing cohort of FGFR-inhibitor naive patients

in a second-line or later setting receiving derazantinib monotherapy at

a dose of 300 mg per day, this cohort will not be further expanded and

Basilea will focus patient enrolment on the intensified dose regimen of

400 mg per day, with the goal to maximize efficacy in this patient

population. The approach is based on the available clinical data and

supported by pharmacology data.

Dr. Engelhardt commented: "Derazantinib monotherapy at a dose of 300 mg

per day has shown to be efficacious and safe in patients with iCCA, and

has also provided signs of clinical benefit in the ongoing FIDES-02

urothelial cancer study. The unmet medical need in advanced urothelial

cancer remains high. At the same time new standard-of-care treatment

options are evolving and the benchmarks of anticancer efficacy for new

treatments are increasing. Derazantinib dose levels above 300 mg per day

have previously been studied and we believe that the intensified dose

regimen of 400 mg per day could provide additional overall clinical

benefit in advanced urothelial cancer."

FIDES-03: Gastric cancer

Dr. Engelhardt added: "We believe that patients with advanced gastric

cancer may also benefit from an intensified dose regimen of

derazantinib. We will therefore amend the FIDES-03 study to explore a

dose of 400 mg per day going forward."

Future data readouts

Basilea continues to expect the first interim efficacy results from the

FIDES-02 urothelial cancer study, in patients at a dose of 300 mg per

day, refractory to prior FGFR-inhibitor treatment, in both monotherapy

and in combination with atezolizumab, in the second half of 2021.

Initial results from cohorts utilizing the intensified dose regimen of

derazantinib 400 mg per day are expected in the first half of 2022. For

FIDES-02 in urothelial cancer, this will include interim efficacy data

as monotherapy, in a second- and post-second-line setting, as well as

atezolizumab combination data in the first-line treatment of

cisplatin-ineligible patients. For FIDES-03 in gastric cancer, this will

include interim efficacy data with derazantinib in monotherapy and the

recommended phase 2 dose (RP2D) of derazantinib combined with

ramucirumab and paclitaxel.

The results from cohort 1 of FIDES-01 and the interim results from the

300 mg per day monotherapy cohort in FGFR-inhibitor naive patients in a

second-line or later setting of FIDES-02 will be published upon

completion of the cohorts at future scientific conferences.

About derazantinib

Derazantinib is an investigational orally administered small-molecule

FGFR inhibitor with strong activity against FGFR1, 2, and 3.(4) FGFR

kinases are key drivers of cell proliferation, differentiation and

migration. FGFR genetic aberrations, e.g. gene fusions, mutations or

amplifications, have been identified as potentially important

therapeutic targets for various cancers, including intrahepatic

cholangiocarcinoma (iCCA), urothelial, breast, gastric and lung

cancers.(5) In these cancers, FGFR genetic aberrations are found in a

range of 5% to 30%.(6)

Derazantinib also inhibits the colony-stimulating-factor-1-receptor

kinase (CSF1R).(4, 7) CSF1R-mediated signaling is important for the

maintenance of tumor-promoting macrophages and therefore has been

identified as a potential target for anti-cancer drugs.(8) Pre-clinical

data has shown that tumor macrophage depletion through CSF1R blockade

renders tumors more responsive to T-cell checkpoint immunotherapy,

including approaches targeting PD-L1/PD-1.(9) (,) (10)

Derazantinib has demonstrated antitumor activity and a manageable safety

profile in a previous biomarker-driven phase 1/2 study in iCCA patients,

(11) and has received U.S. and EU orphan drug designation for iCCA.

Basilea is currently conducting three clinical studies with

derazantinib. The first study, FIDES-01, is a phase 2 study in patients

with inoperable or advanced iCCA. It comprises one cohort of patients

with FGFR2 gene fusions and another cohort of patients with mutations or

amplifications.(1) The second study, FIDES-02, is a phase 1/2 study

evaluating derazantinib alone and in combination with Roche's PD-L1

checkpoint inhibitor, atezolizumab, in patients with advanced urothelial

cancer, including metastatic, or recurrent surgically unresectable

disease, expressing FGFR genetic aberrations.(12) The third study,

FIDES-03, is a phase 1/2 study evaluating derazantinib alone and in

combination with Lilly's anti-VEGFR2 antibody ramucirumab and paclitaxel,

or with Roche's PD-L1 checkpoint inhibitor atezolizumab, in patients

with advanced gastric cancer with FGFR genetic aberrations.(13) Basilea

has in-licensed derazantinib from ArQule Inc., a wholly-owned subsidiary

of Merck & Co., Inc., Kenilworth, N.J., U.S.A.

About intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is a cancer originating from the

biliary system. The age-adjusted incidence rate of iCCA in the United

States has been increasing over the past decade and is currently

estimated to be approximately 1.2 per 100,000.(14) Patients are often

diagnosed with advanced or metastatic disease that cannot be surgically

removed. Current first-line standard of care is the chemotherapy

combination of gemcitabine and platinum-derived agents. The prognosis

for patients with advanced disease is poor, with a median survival of

less than one year.(15)

About urothelial cancer

These cancers start in the urothelial cells that line the inside of the

bladder. 80,000 new cases of bladder cancer have been estimated in the

U.S. for 2017. Up to 20% of patients will have muscle-invasive disease

and present with or will later develop metastases.(16) FGFR gene

aberrations occur in about 15-20% of advanced urothelial cancers.(17) (,

) (18) For patients with advanced urothelial cancer, outcomes can be

poor due to the often rapid progression of the tumor and the lack of

efficacious treatments, especially in relapsed or refractory disease.

About gastric cancer

Gastric cancer is the fifth most common cancer worldwide and the third

most lethal cancer type.(19) Median survival rarely exceeds twelve

months and the five-year-survival is less than 10%.(20) Basilea

estimates that there are approximately 190,000 new cases of gastric

cancer per year in total across the EU top 5 countries, Japan and the

U.S. FGFR genetic aberrations have been observed in about 10% of gastric

cancers.(21)

About Basilea

Basilea is a commercial-stage biopharmaceutical company founded in 2000

and headquartered in Switzerland. We are committed to discovering,

developing and commercializing innovative drugs to meet the medical

needs of patients with cancer and infectious diseases. We have

successfully launched two hospital brands, Cresemba for the treatment of

invasive fungal infections and Zevtera for the treatment of severe

bacterial infections. We are conducting clinical studies with two

targeted drug candidates for the treatment of a range of cancers and

have a number of preclinical assets in both cancer and infectious

diseases in our portfolio. Basilea is listed on the SIX Swiss Exchange

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May 31, 2021 01:15 ET (05:15 GMT)