Press Release: Basilea announces completion of patient enrolment into first cohort of phase 2 study FIDES-01 with derazantinib in bile duct cancer (iCCA)

Basel, Switzerland, July 20, 2020

Basilea Pharmaceutica Ltd. (SIX: BSLN) announced today the completion of

patient enrolment into the first cohort of the phase 2 registrational

study, FIDES-01, assessing the activity of the FGFR kinase inhibitor

derazantinib in patients with intrahepatic cholangiocarcinoma (iCCA), a

form of bile duct cancer. This first cohort enrolled patients with iCCA

expressing fusions of the fibroblast growth factor receptor 2 (FGFR2)

gene and reached its target enrolment of 100 patients.

The FIDES-01 (Fibroblast growth factor Inhibition with DErazantinib in

Solid tumors)(1) study is a multi-center, open-label phase 2

registrational study of once-daily oral derazantinib for the treatment

of patients with inoperable or advanced iCCA and FGFR2 gene fusions or

FGFR2 gene mutations or amplifications. In January 2019, a pre-planned

interim analysis of the FGFR2 gene fusion-positive cohort of the study

showed promising efficacy in this patient population and also confirmed

the safety profile and tolerability of derazantinib observed previously

in the clinical program.(2, 3)

Dr. Marc Engelhardt, Chief Medical Officer, said: "Topline data from the

first FIDES-01 cohort of FGFR2 gene fusion-positive patients are

expected to become available towards year-end. These data will be

important to help define our regulatory strategy in iCCA. With the FIDES

range of studies, FIDES-01, FIDES-02 and FIDES-03, our goal is to

leverage the unique properties of derazantinib, for the benefit of

patients with advanced FGFR-driven cancers in iCCA, urothelial and

gastric cancer."

Enrolment into the second cohort of FIDES-01 is ongoing. This cohort is

assessing the activity of derazantinib in patients with FGFR2 gene

mutations or amplifications, thus broadening the range of investigated

FGFR2-driven tumors. Interim data from this second cohort are expected

to become available in the second half of 2020. The results from the

second cohort will support defining the full therapeutic potential of

derazantinib in iCCA and potentially further strengthen the

differentiation of derazantinib from other FGFR inhibitors. In addition,

the clinical development program for derazantinib includes two further

Phase 1b/2 studies, the ongoing FIDES-02 in patients with urothelial

cancer and the planned FIDES-03, in patients with advanced gastric

cancer, which is expected to start in Q3 2020.(4)

About derazantinib

Derazantinib is an investigational orally administered small-molecule

FGFR kinase inhibitor with strong activity against FGFR1, 2, and 3.(5)

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

range of 5% to 30%.(7)

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

kinase (CSF1R).(5, 8) 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.(9) 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.(10, 11) Derazantinib has

demonstrated antitumor activity and a manageable safety profile in a

previous biomarker-driven phase 1/2 study in iCCA patients,(2) and has

received U.S. and EU orphan drug designation for iCCA. Basilea is

currently conducting two clinical studies with derazantinib. The first

study, FIDES-01, is a registrational 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-blocking immune-checkpoint inhibitor atezolizumab (Tecentriq(R)

)(12) in patients with advanced urothelial cancer, including metastatic,

or recurrent surgically unresectable disease, expressing FGFR genetic

aberrations.(4) Basilea in-licensed derazantinib from ArQule Inc, a

wholly-owned subsidiary of Merck & Co., Inc., Kenilworth, N.J., U.S.A.

About intrahepatic cholangiocarcinoma (iCCA)

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.(13) 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.(14)

About Basilea

Basilea Pharmaceutica Ltd. is a commercial-stage biopharmaceutical

company, focused on the development of products that address the medical

challenges in the therapeutic areas of oncology and infectious diseases.

With two commercialized drugs, the company is committed to discovering,

developing and commercializing innovative pharmaceutical products to

meet the medical needs of patients with serious and life-threatening

conditions. Basilea Pharmaceutica Ltd. is headquartered in Basel,

Switzerland and listed on the SIX Swiss Exchange (SIX: BSLN). Additional

information can be found at Basilea's website www.basilea.com.

Disclaimer

This communication expressly or implicitly contains certain

forward-looking statements, such as "believe", "assume", "expect",

"forecast", "project", "may", "could", "might", "will" or similar

expressions concerning Basilea Pharmaceutica Ltd. and its business,

including with respect to the progress, timing and completion of

research, development and clinical studies for product candidates. Such

statements involve certain known and unknown risks, uncertainties and

other factors, which could cause the actual results, financial condition,

performance or achievements of Basilea Pharmaceutica Ltd. to be

materially different from any future results, performance or

achievements expressed or implied by such forward-looking statements.

Basilea Pharmaceutica Ltd. is providing this communication as of this

date and does not undertake to update any forward-looking statements

contained herein as a result of new information, future events or

otherwise.

For further information, please contact:

Peer Nils Schröder, PhD

Head of Corporate Communications & Investor Relations

Phone +41 61 606 1102

E-mail media_relations@basilea.com

investor_relations@basilea.com

This press release can be downloaded from www.basilea.com.

References

1. FIDES-01: ClinicalTrials.gov identifier: NCT03230318

2. V. Mazzaferro, B. F. El-Rayes, M. Droz dit Busset et al. Derazantinib

(ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive

intrahepatic cholangiocarcinoma. British Journal of Cancer 2019 (120),

165-171. ClinicalTrials.gov identifier: NCT01752920

3. K. P. Papadopoulos, B. F. El-Rayes, A. W. Tolcher et al. A phase 1 study

of ARQ 087, an oral pan-FGFR inhibitor in patients with advanced solid

tumours. British Journal of Cancer 2017 (117), 1592-1599.

ClinicalTrials.gov identifier: NCT01752920

4. FIDES-02: ClinicalTrials.gov identifier: NCT04045613.

5. T. G. Hall, Y. Yu, S. Eathiraj et al. Preclinical activity of ARQ 087, a

novel inhibitor targeting FGFR dysregulation. PLoS ONE 2016, 11 (9),

e0162594

6. R. Porta, R. Borea, A. Coelho et al. FGFR a promising druggable target in

cancer: Molecular biology and new drugs. Critical Reviews in

Oncology/Hematology 2017 (113), 256-267

7. T. Helsten, S. Elkin, E. Arthur et al. The FGFR landscape in cancer:

Analysis of 4,853 tumors by next-generation sequencing. Clinical Cancer

Research 2016 (22), 259-267

8. P. McSheehy, F. Bachmann, N. Forster-Gross et al. Derazantinib (DZB): A

dual FGFR/CSF1R-inhibitor active in PDX-models of urothelial cancer.

Molecular Cancer Therapeutics 2019 (18), 12 supplement, pp. LB-C12

9. M. A. Cannarile, M. Weisser, W. Jacob et al. Colony-stimulating factor 1

receptor (CSF1R) inhibitors in cancer therapy. Journal for ImmunoTherapy

of Cancer 2017, 5:53

10. Y. Zhu, B. L. Knolhoff, M. A. Meyer et al. CSF1/CSF1R Blockade reprograms

tumor-infiltrating macrophages and improves response to T cell checkpoint

immunotherapy in pancreatic cancer models. Cancer Research 2014 (74),

5057-5069

11. E. Peranzoni, J. Lemoine, L. Vimeux et al. Macrophages impede CD8 T cells

from reaching tumor cells and limit the efficacy of anti--PD-1 treatment.

Proceedings of the National Academy of Science of the United States of

America 2018 (115), E4041-E4050

12. Tecentriq(R) is a registered trademark of Hoffmann-La Roche Ltd.

13. S. K. Saha, A. X. Zhu, C. S. Fuchs et al. Forty-year trends in

cholangiocarcinoma incidence in the U.S.: intrahepatic disease on the

rise. The Oncologist 2016 (21), 594-599

14. A. Lamarca, D. H. Palmer, H. S. Wasa et al. ABC-06 | A randomised phase

III, multi-centre, open-label study of Active Symptom Control (ASC) alone

or ASC with oxaliplatin/5-FU chemotherapy (ASC+mFOLFOX) for patients

(pts) with locally advanced/metastatic biliary tract cancers (ABC)

previously-treated with cisplatin/gemcitabine (CisGem) chemotherapy.

Journal of Clinical Oncology 2019 (37), supplement, abstract 4003

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