Philogen Spa · MIL:PHIL
Philogen Spa — H1 2024 Earnings Presentation
44 slides from Philogen Spa's earnings presentation, Oct 1, 2024
Slide 1: Webinar 1H 2024 Results
Webinar 1H 2024 Results 1 October 2024 Prof. Dr. Dario Neri Dr. Laura Baldi Dr. Emanuele Puca
Slide 2: Forward Looking Statements
Forward Looking Statements The forward-looking statements contained in this presentation may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of t
Slide 3: The Philogen Group
The Philogen Group Headquarters Discovery Center Antibody Therapeutics Small Molecule Therapeutics Zurich Siena Listed on the Italian Stock Exchange Collaborations with large pharmaceutical companies over the years 3
Slide 4: Philogen's approach to targeted cancer therapy
Philogen’s approach to targeted cancer therapy Philogen focuses on the ligand-based delivery of bioactive payloads Discovery Tools (Ligands) Payloads Antibodies Small molecules Cytotoxic Radionuclide Drug Target Target protein protein DNA- Antibody Encoded Ligand Payload Chemical Cytokine Phage Disp
Slide 5: Targeted delivery based on antibodies and small molecules
Targeted delivery based on antibodies and small molecules Chemotherapy [1] IgG Antibody [2] Antibody Fragment [3] Targeted Small Molecule [4] O OH HO O H H O NH O O O O OH O OH O O No tumor uptake Slow tumor uptake Liver Liver Fast Ultra fast tumor uptake tumor uptake Mesothelioma Colon Cancer Breas
Slide 6: Clinical-stage pipeline
Clinical-stage pipeline Product Partnered? Indication Preclinical Phase I Phase II Phase III NidlegyTM Stage III B,C Melanoma (EU) Marketing Authorization Application Stage III B,C Melanoma (US) Registration potential Stage IV Melanoma Nonmelanoma Skin Cancer (BCC/SCC) Fibromun + doxorubicin Soft-Ti
Slide 7: Clinical-stage pipeline
Clinical-stage pipeline Product Partnered? Indication Preclinical Phase I Phase II Phase III NidlegyTM Stage III B,C Melanoma (EU) Marketing Authorization Application Stage III B,C Melanoma (US) Registration potential Stage IV Melanoma Nonmelanoma Skin Cancer (BCC/SCC) Fibromun + doxorubicin Soft-Ti
Slide 8: Dermato-Oncology − Conditions and unmet medical need
Dermato-Oncology − Conditions and unmet medical need Healthy epidermis Melanoma, Basal Cell Carcinoma (BCC), and Squamous Cell Carcinoma Squamous (SCC) are the most common types of skin cancer and represent a cell large unmet medical need. Melanocyte Basal cell New cases (US, 2023) 97,6101 Melanoma
Slide 9: Nidlegy – Overview
Nidlegy™ – Overview Two targeted active ingredients… …administered in combination… …intralesionally Proprietary L19 Antibody Antibody ANTIBODY First ever NIDLEGYTM Fragment (anti-EDB Fibronectin) combination pack approved by EMA in oncology Selective localization at tumor sites IL2 TNF PAYLOADS Immu
Slide 10: Developments in Melanoma
Developments in Melanoma Developments in Europe § Phase III trial reached the primary enpoint RFS § Data presented at ASCO 2024 on May 31, 2024 § Marketing Authorization Application submitted to EMA on June 3, 2024 (the dossier has been validated) § CHMP opinion expected in mid 2025 Developments in
Slide 11: Opportunities in locally advanced BCC
I d1 J d15 K d22 L Opportunities in locally advanced BCC Biopsies at (")*.. (")*.. !"#$B&D$ M (")*/0 (")*/0 (")*+ N (")*0/ (")*0/ (")*,- OBiopsies at P baseline end of d36 d63 Basal Cell Carcinoma (BCC) Baseline treatment § 4 million new cases in the US every year 1 Tumor § ~ 0.8-2% locally advanced
Slide 12: Opportunities in locally advanced cSCC
Opportunities in locally advanced cSCC Cutaneous Squamous Cell Carcinoma (cSCC) Baseline d8 d196 Patient_24_1.9.23 § 1.1 million new cases in the US every year 1 pCR § ~ 5% locally advanced; kills more than melanoma 2 W3_ Pt_24 § CR rate of approved drugs 13% 3 W1_ d22 d92 § Current CR-rate ~ 47% wi
Slide 13: Opportunities in Kaposi Sarcoma
Opportunities in Kaposi Sarcoma Example 1 Baseline Day 15 Day 31 Day 78 Kaposi Sarcoma Day 1 § ~ 2’000 new cases in the US every year 1 § Standard therapies involve surgery, radiation, or chemotherapy § High unmet medical need CR 2x EU Phase II studies >20 sites Example 2 BL D1 D8 D5 D76 CR 3/10 pat
Slide 14: Developments in Non Melanoma Skin Cancers
Developments in Melanoma in Non Melanoma Skin Cancers Developments in Europe § Promising results with Nidlegy™ in the on-going Phase II trials in LaBCC and LacSCC Global developments § Philogen has organised an Advisory Board with Key Opinion Leaders from leading European and US centers § The goal w
Slide 15: Clinical-stage pipeline
Clinical-stage pipeline Product Partnered? Indication Preclinical Phase I Phase II Phase III NidlegyTM Stage III B,C Melanoma (EU) Marketing Authorization Application Stage III B,C Melanoma (US) Registration potential Stage IV Melanoma Nonmelanoma Skin Cancer (BCC/SCC) Fibromun + doxorubicin Soft-Ti
Slide 16: Glioblastoma and Soft Tissue Sarcomas − unmet medical need
Glioblastoma and Soft Tissue Sarcomas − unmet medical need With current standard therapies, Glioblastoma and advanced Soft Tissue Sarcoma are incurable cancers Glioblastoma New cases (US, 2023) 15,000 Deaths (US, 2023) >10,000 mOS of pts with recurrent GBM ~ 5.6 - 9.8 months Soft Tissue Sarcoma New
Slide 17: Fibromun - Overview
Fibromun - Overview L19-TNF Targeted active ingredient… …administered systemically… …selectively localizes to tumors ANTIBODY L19 Antibody L19TNF 50 F9 teratocarcinoma mouse model 6 24h post injection Selective localization to EDB(+) 40 Fibronectin tumors 4 30 %ID/g %ID/g 20 2 PAYLOAD Cytokine TNF 1
Slide 18: Strategic Licensing Agreement with Sun Pharma
Strategic Licensing Agreement with Sun Pharma Deal Summary § Commercial Agreement with Sun Pharma § >41’000 employees (from 38k in 2023) The Partner § Market Cap ~ 52 Bln USD (from ~ 27 Bln USD in 2023) § Operates in >100 countries § Revenues ~ 6 Bln USD § Commitment to specialty products Sun Pharma
Slide 19: Fibromun programs in Glioblastoma
Fibromun programs in Glioblastoma Development Program Glioblastoma § GLIOSUN Phase I/II/IIb study in CH: L19TNF in combination with chemoradiotherapy for newly diagnosed GBM § GLIOSTAR Phase I/II study in EU: L19TNF in combination with lomustine for GBM at first progression § GLIOSTELLA Phase II stu
Slide 20: Fibromun programs in Soft Tissue Sarcoma (STS)
Fibromun programs in Soft Tissue Sarcoma (STS) Three ongoing registration trials Active clinical centers 1. Phase III EU study – combination with doxorubicin § 1L STS with up to 118 patients 2. Phase IIb US study – combination with doxorubicin 1L study 25 centers active § 1L Leiomyosarcoma with up t
Slide 21: Clinical-stage pipeline
Clinical-stage pipeline Product Partnered? Indication Preclinical Phase I Phase II Phase III NidlegyTM Stage III B,C Melanoma (EU) Marketing Authorization Application Stage III B,C Melanoma (US) Registration potential Stage IV Melanoma Nonmelanoma Skin Cancer (BCC/SCC) Fibromunc + doxorubicin Soft-T
Slide 22: Dr. Samuele Cazzamalli Received 2024 EFMC Young Medicinal Chemist Award
Dr. Samuele Cazzamalli (Head of Chemistry) Has Received the 2024 EFMC Young Medicinal Chemist in Industry Award 22
Slide 23: From antibodies to small molecules for pharmacodelivery
From antibodies to small molecules for pharmacodelivery Small organic Antibody molecule 24h 1h in BLUE = tumor 7 days 1 hour in BLUE = tumor in GREEN = antibody in GREEN = small molecule Slow & heterogeneous Rapid & selective accumulation in tumors accumulation in tumors Small organic molecules show
Slide 24: Development of small molecule therapeutics: payload options
Development of small molecule therapeutics: payload options Discovery DNA-Encoded Libraries Small molecule for targeted delivery Radionuclide conjugates Adaptors for universal CAR-T cells Oncology and beyond Oncology Cytotoxic drug-conjugates Immunomodulatory drug-conjugates Oncology Oncology and be
Slide 25: Tumor targeting with small organic ligands
Tumor targeting with small organic ligands FAP CAIX PSMA SSTR2 ACP-3 OncoFAP & AAZ PSMA-617 Octreotate OncoFAP-23 Solid tumors Renal cell carcinoma Prostate cancer Neuroendocrine tumors New ligand discovered via DEL (undisclosed structure) KD = ~100 pM See next slide 1h 1h 0.5h 6h Philogen is develo
Slide 26: Tumor targeting with small organic ligands
Tumor targeting with small organic ligands FAP CAIX PSMA SSTR2 ACP-3 OncoFAP & AAZ PSMA-617 Octreotate OncoFAP-23 Solid tumors Renal cell carcinoma Prostate cancer Neuroendocrine tumors New ligand discovered via DEL (undisclosed structure) KD = ~100 pM See next slide 1h 1h 0.5h 6h Philogen is develo
Slide 27: Development of small molecule therapeutics: payload options
Development of small molecule therapeutics: payload options Discovery DNA-Encoded Libraries Small molecule for targeted delivery Radionuclide conjugates Adaptors for universal CAR-T cells Oncology and beyond Oncology Cytotoxic drug-conjugates Immunomodulatory drug-conjugates Oncology Oncology and be
Slide 28: OncoFAP platform
OncoFAP platform Imaging § More than 200 patients imaged with 68Ga-OncoFAP § Phase I trial completed (with dosimetry) § Collaboration with Blue Earth Diagnostics Therapy § First 3 patients treated with 177Lu-OncoFAP-23 § Phase I trial approved Breast cancer § Patients have received up to 3 dose, whi
Slide 29: Development of small molecule therapeutics: payload options
Development of small molecule therapeutics: payload options Discovery DNA-Encoded Libraries Small molecule for targeted delivery Radionuclide conjugates Adaptors for universal CAR-T cells Oncology and beyond Oncology Cytotoxic drug-conjugates Immunomodulatory drug-conjugates Oncology Oncology and be
Slide 30: FAP-targeted small molecule-drug conjugates
FAP-targeted small molecule-drug conjugates FAP OncoFAP -GlycineProline- Cytotoxic Payload Targeting moiety Cleavable linker (MMAE, Topoisomerase-I inhibitor) Ultra-high affinity for FAP FAP substrate Kd = 0.6 nM § FAP is a post-proline endopeptidase, with high selectivity for the GlyPro sequence §
Slide 31: Phase I study in animal patients: trial design
Phase I study in animal patients: trial design N=6 3.5 mg/m2 Dose expansion if no Goal 1: Safety Goal 2: Efficacy 6.0 mg/m2 de-escalation is necessary Weekly measurement of 8.5 mg/m2 Weekly assessment of target lesions and CT toxicities and quality of 10.0 mg/m2 10.0 mg/m2 10.0 mg/m2 scan at Day 0 a
Slide 32: Phase I study in animal patients: results
Phase I study in animal patients: results Goal 1: Safety Goal 2: Efficacy 40 30 20 Change from baseline [%] 10 PD 0 Treatment was well tolerated -10 SD -20 SD No signs of clinical or hematological toxicity -30 PR PR (only one gastrointestinal Grade 1 AE ) -40 -50 -60 Easy Boris Birba Coco 1 Coco 2 3
Slide 33: The success story of Coco
The success story of Coco Recurrence of the tumor First treatment cycle 10/2023 Second treatment cycle 06/2024 3.5 mg/m2 OncoFAP-GlyPro-MMAE 10.0 mg/m2 OncoFAP-GlyPro-MMAE Before treatment Before treatment 29 mm 148 mm After 4 injections After 4 injections 14 mm 73 mm No signs of toxicity were obser
Slide 34: Tumor targeting with small organic ligands
Tumor targeting with small organic ligands FAP CAIX PSMA SSTR2 ACP-3 OncoFAP & AAZ PSMA-617 Octreotate OncoFAP-23 Solid tumors Renal cell carcinoma Prostate cancer Neuroendocrine tumors New ligand discovered via DEL (undisclosed structure) KD = ~100 pM See next slide 1h 1h 0.5h 6h Philogen is develo
Slide 35: The market of PSMA radiopharmaceuticals in prostate cancer
The market of PSMA radiopharmaceuticals in prostate cancer Imaging Pylarify® Therapy Pluvicto® FDA FDA App App r r 1200 2021 oval 1600 2022 oval Sales in Mio USD Sales in Mio USD 1200 800 800 400 400 0 0 2021 2022 2023 2024 (est.) 2022 2023 2024 (est.) • The radiopharmaceutical market for prostate c
Slide 36: Pluvicto for the treatment of metastatic prostate cancer
Pluvicto® for the treatment of metastatic prostate cancer VISION Phase III trial Uptake in healthy organs Uptake in salivary glands All patients progress Uptake in kidneys § PSMA, the target of Pluvicto®, is expressed in normal organs (e.g., salivary glands, kidneys) § It would be desirable to have
Slide 37: PSMA vs. ACP3: ACP3 is cleaner in healthy tissues
PSMA vs. ACP3 ACP3 is cleaner than PSMA in healthy tissues PSMA ACP3 Apart from prostate (which is normally resected), PSMA is expressed in certain normal organs (salivary glands, GI tract, kidney), whereas ACP3 is completely undetectable 37
Slide 38: PSMA vs. ACP3: ACP3 more abundant in prostate cancer
PSMA vs. ACP3 ACP3 is more abundant than PSMA in prostate cancer PSMA ACP3 Serial sections of the same patient tissue allow a side-by-side comparison of PSMA vs. ACP3 expression in prostate tumors of different Gleason score 38
Slide 39: A comparative immunohistochemical analysis
A comparative immunohistochemical analysis Gleason 7 (4 + 3) H-score ACP3 3 2 1 PSMA 0 Gleason 7 (3 + 4) ACP3 PSMA Gleason 6 ACP3 PSMA 39
Slide 40: A comparative immunohistochemical analysis
A comparative immunohistochemical analysis Gleason 8 (4 + 4) H-score ACP3 3 PSMA 2 1 Gleason 9 (4 + 5) 0 ACP3 PSMA Metastases lung bronchus pleura lymph n. omentum bone bladder ACP3 PSMA Comparative immunohistochemical analysis ACP3 is strongly expressed (H-score = 3) in 34/39 samples (87%) while PS
Slide 41: OncoACP3 – In vivo biodistribution and therapy
OncoACP3 – In vivo biodistribution and therapy Tumor Targeting Tumor Therapy (177Lu-OncoACP3) (177Lu-OncoACP3) Tumor growth 1000 177 15 177 Lu-OncoACP3-DOTAGA 5 MBq (1/4 CR) Lu- ! Body weight change (%) 177 177 Lu-OncoACP3-DOTAGA 20 MBq (4/4 CR) Lu- Tumor volume (mm3) 10 800 Vehicle Ultra low dose!!
Slide 42: Summary
Summary § The Radiopharmaceutical Market for prostate cancer is driven by PSMA-targeting ligands and is worth more than 3 billion USD § PSMA has liabilities in normal organs which are problematic for imaging and especially for therapy § ACP3 is completely undetectable in normal organs (except for pr
Slide 43: Financials 1H 2024
Financials 1H 2024 § CONSOLIDATED REVENUES of € 1,7mln vs € 22,5 mln in 1 H23 § The Group does not have a steady stream of revenues yet § OPEX stood at €16,9 mln: + 22% compared to 1H2023 § Accelerating clinical trials and expanding manufacturing activities § EBITDA of € (15,2) AND NET RESULT (15,5)
Slide 44: Thank you
Thank you Philogen SpA Piazza La Lizza ⎮ 7 53100 Siena (SI) ⎮ Italy