On December 1, 2022 Philogen S.p.A. (BIT:PHIL), a clinical-stage biotech company focused on the development of
innovative medicines based on tumor targeting antibody and small molecule ligands, is pleased to provide an update on its R&D programs (Press release, Philogen, DEC 1, 2022, View Source [SID1234624689]).
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Dario Neri, co-founder, CEO and CSO of Philogen, commented: "We are very pleased with the recent progress of our pipeline. We currently have seven pivotal clinical trials underway with Nildegy and Fibromun for which we expect important readouts in the coming years. Our most advanced study is the one of Nidlegy in stage IIIB,C melanoma and we expect to reach 95 events to complete the trial in 2023.
Based on the complete remissions being observed with Nidlegy in high-risk Basal Cell Carcinoma (BCC), the Company is committed to expand the number of clinical centers to speed up timelines. It is important to highlight that the market potential in high-risk BCC is potentially larger than the melanoma market. We have the ambition to turn Nidlegy into a broad applicable dermato-oncology drug.
Fibromun’s registration studies remain on track, both in Soft Tissue Sarcoma and in Glioblastoma.
Our Discovery Center has been very productive, having published more than 15 scientific peer reviewed publications and has initiated
two novel collaborations with Bracco imaging and Janssen which are currently ongoing.
Our Group is increasing its investments in the discovery of small molecule tumor-targeting agents, which may facilitate the selective
delivery of therapeutic radionuclides (Small Molecule Radiolabeled Conjugates, or "SMRCs") and of non-radioactive drugs (Small
Molecule Drug Conjugates, or "SMDCs"). The excellent targeting properties of our OncoFAP small molecule ligand bode well for
delivering both therapeutic radionuclides and cytotoxic drugs to tumors. Stimulated by curative activity observed in "difficult-to-treat"
preclinical models of cancer, preparation activities for therapeutic trials with the OncoFAP platform are ongoing."
MAIN EVENTS AND RECENT HIGHLIGHTS
• Nidlegy – consists of two active ingredients, L19IL2 and L19TNF which are given intratumorally. The L19 antibody is specific
to the Extra Domain B of Fibronectin, a protein expressed in tumors (and other diseases) but absent in most healthy tissues.
Interleukin 2 (IL2) and Tumor Necrosis Factor (TNF) are inflammatory cytokines with anti-tumor activities
o Phase III European study in neoadjuvant (i.e., prior surgery) Stage IIIB,C melanoma (Pivotal)
▪ 214 patients have been enrolled, in line with the protocol of the study
▪ The trial will read-out when 95 events are reached. One event occurs when a patient’s tumor relapses
or when the patient passes away. As of December 1st, 80 out of 95 events have been recorded
▪ The study is ongoing in Germany, Italy, Poland, and France at 22 clinical centers
▪ The study has successfully passed two interim analyses in March 2019 (at 25% of total events) and
December 2020 (at 50% of total events). An independent Data and Safety Monitoring Board supported
the continuation of the trial based on Safety and Futility analyses
o Phase III USA study in neoadjuvant Stage IIIB,C melanoma (Neodream)
▪ The study is ongoing in the United States, Switzerland, and Spain at 23 clinical centers. More than 30
centers are expected to be open by 1H 2023.
▪ A larger number of centers are being activated, compared to the European trial described above to
speed up recruitment rate
o Phase II study in high-risk Basal Cell Carcinoma and cutaneous Squamous Cell Carcinoma (cSCC) (Duncan)
▪ Nine out of 40 patients have been enrolled. Eight patients were suffering from high-risk BCC and one
had cSCC
▪ The study is ongoing in Switzerland, Germany, and Poland. Seven clinical centers are currently open
and at least an additional site is expected to be activated by 1H 2023. Evidence of potent therapeutic
activity has emerged from the study and results have been presented at congresses in the field.
o Phase II study in a basket of Non-Melanoma Skin Cancers (NMSC) (Intrinsic)
▪ The trial has just started and foresees the treatment of 70 patients
▪ NMSC included in the trial are Kaposi’s sarcoma, cutaneous T-cell lymphoma, malignant adnexal tumors
of the skin, Keratocanthoma, Merkel Cell Carcinoma, cutaneous Squamous Cell Carcinoma, and Basal
Cell Carcinoma
▪ The study is ongoing in Italy and France. Three centers are currently open and at least two additional
sites are expected to be activated by 1H 2023
• Fibromun – a fully-human immunomodulatory product consisting of the L19 antibody and TNF (a strong pro-inflammatory
cytokine). Fibromun is administered by systemic intravenous infusion
o Phase III European study in newly diagnosed advanced or metastatic Soft Tissue Sarcoma (Fibrosarc)
▪ Fibromun is given in combination with Doxorubicin
▪ 47 out of 118 patients have been enrolled
▪ The study is ongoing in Germany, Italy, Spain, Poland, and soon also in France. 17 centers are currently
open and more than 25 are expected to be activated by 1H 2023
▪ The opening of the centers and the recruitment of patients are on track. The projections support the
completion of patient enrolment by the end of 2023
o Phase IIb USA study in newly diagnosed metastatic Leiomyosarcoma (Fibrosarc US)
▪ Fibromun is given in combination with Doxorubicin
▪ Leiomyosarcoma is the most common Soft Tissue Sarcoma subtype
▪ 9 clinical centers are currently open
o Phase II EU study in advanced or metastatic Soft Tissue Sarcoma patients that failed at least 2 prior systemic
therapies (Flash)
▪ Fibromun is given in combination with Dacarbazine
▪ 20 out of 92 patients have been enrolled
▪ Seven centers are currently open and more than 15 are expected to be activated by 1H 2023
o Phase I/II study in progressive High-Grade Stage III-IV Glioma (Gliomoon)
▪ Fibromun is given as monotherapy
▪ 20 out of 20 patients have been enrolled. The last patient was recruited in December 2020
▪ The study has been conducted at three clinical centers in Switzerland
▪ Data clean-up is ongoing and full results will be presented in a peer-reviewed scientific publication
o Phase I/II study in progressive Glioblastoma (Gliostar)
▪ Fibromun is given in combination with Lomustine
▪ 14 patients have been enrolled in the Phase I part. Cohort 1 and 2 have been completed, while Cohort
3 is ongoing. Cohort 3 is the last one before proceeding to the Phase II randomized part
▪ Substantially improved survival benefit and major durable responses observed both in Cohort 1 and
Cohort 2. Objective responses are very uncommon with lomustine alone
▪ More mature data of Cohorts 2 and 3 will be available in 1H 2023
▪ The randomized Phase II part of the study foresees 158 patients and is expected to start in 1H 2023
▪ The Phase I trial is currently ongoing at the University Hospital Zürich. Philogen has alreadycontacted
several centers in Switzerland, Italy, France, Germany, and in the USA, with the aim to open 18-20 sites
for the Phase II randomized part of the study
o Phase I/II/IIb study in newly-diagnosed Glioblastoma (Gliosun)
▪ Fibromun is given in combination with radiotherapy and temozolomide
▪ 9 patients have been enrolled in the Phase I part. Cohort 1 and 2 have been completed, while Cohort 3
is ongoing. 5 Cohorts in total are planned for Phase I, before proceeding to the Phase II single-arm part
▪ The Phase II part with 32 patients is expected to start in 2023
▪ The randomized Phase IIb part, with registration potential, foresees 166-206 and is expected to start
when consolidated data of Phase II become available
• OncoFAP is a small molecule ligand with ultra-high affinity for Fibroblast Activation Protein (FAP). The product is suitable
for diagnostic and therapeutic applications of a variety of metastatic solid tumors, as FAP is overexpressed in more than
90% of epithelial cancers (e.g., malignant breast, colorectal, ovarian, lung, skin, prostate, and pancreatic cancers, as well as
in some soft tissue and bone sarcomas)
o OncoFAP – radio-conjugate for imaging applications
▪ Several patients suffering from different cancers have already been imaged in Germany with 68GaOncoFAP
▪ The Italian Medicines Agency AIFA approved the Clinical Trial Application to formally initiate a Phase I
clinical trial in Italy. The first patient of the study is expected in the upcoming weeks
Main Office: Loc. Bellaria, 35 – 53018 Sovicille (SI), Italy
e-mail: [email protected] – website: www.philogen.com
o OncoFAP-23 – radio-conjugate for therapy applications
▪ OncoFAP-23 is an innovative derivative which shows excellent tumor targeting properties in pre-clinical
studies. The product selectively localizes rapidly into neoplastic lesions, with a stable uptake in the
tumor for at least 96h. The long-tumor residence time of the novel OncoFAP derivative bodes well for
therapeutic applications
▪
177Lu-OncoFAP-23 exerts potent anti-cancer activity in pre-clinical studies, which are superior to other
FAP-targeting agents
▪ The GMP production and central labelling of OncoFAP-23 are ongoing at the dedicated Contract
Research Organization
▪
177Lu-OncoFAP-23 is expected to enter in clinical trials by the end of 2023
o OncoFAP-GlyPro-MMAE – small molecule drug conjugate
▪ The Chemistry Group at Philochem (discovery center of the Philogen Group) has identified and tested
novel OncoFAP-based drug conjugates showing excellent tumor targeting and therapeutic properties
in pre-clinical models.
▪ OncoFAP-GlyPro-MMAE shows superior performance compared to other derivatives featuring
commonly used linkers in Antibody-Drug Conjugates (e.g., Valine-Citrulline linker)
▪ Small Molecule Drug Conjugates are an attractive alternative to ADCs, based on their superior targeting
performance and much lower Cost of Goods
• Ongoing partnerships include those on Dodekin (undisclosed), Dekavil (Pfizer), small molecule for diagnostic applications
(Bracco), and discovery of novel small molecule therapeutics (Janssen)
• GMP Facility in Rosia
o The construction and the equipment of the novel GMP facility in Rosia with state-of-the-art equipment have been
completed within the foreseen timelines.
o Three Aseptic Process Simulations (APS) have recently been successfully accomplished. APS simulates the aseptic
process of the so-called "fill and finish" step of a GMP production campaign and represents a crucial step before
initiating the manufacturing of commercial batches
o Authorization from the Italian Medicines Agency, AIFA of the new GMP production facility in Rosia for the
production and marketing of drugs is expected in 2023
o It should be noted that this new facility will complement the existing GMP plant in Montarioso (Siena), which will
be dedicated to the production of investigational drugs
The Group remains engaged in the strengthening of its in-house R&D, as well as contractual activities related to discovery and/or manufacturing. It also runs Business Development activities with potential industrial partners in order to seek new scientificcollaborations on an opportunistic basis.