Noxopharm Ltd. · ASX:NOX
Noxopharm — TROG ASM Breakfast Symposium 2018
28 slides from Noxopharm's conference presentation, Mar 21, 2018
Slide 1: NOX66 TROG ASM Breakfast Symposium
NOX66 A targeted anti-cancer agent to enhance both direct and indirect radiation-induced tumor cell cytotoxicity following EBRT and brachytherapy radiotherapy TROG ASM BREAKFAST SYMPOSIUM 21 ST MARCH 2018
Slide 2: Agenda
Agenda ▪ Introduction to Noxopharm and NOX66 ▪ Ian Minns ▪ Case Study #1 ▪ Prof. Paul de Souza ▪ Clinical Development pipeline ▪ Dr Isabell Vocks ▪ Case Study #2 ▪ Prof. Paul de Souza
Slide 3: About Noxopharm
About Noxopharm ▪ Australian biotechnology company ▪ ASX listed (NOX) (August 2016) ▪ Oncology focused ▪ Lead candidate (NOX66) in development as an enhancer of radiotherapy and chemotherapy in patients with solid tumours ▪ Non-oncology drug candidates managed via a subsidiary company (Nyrada Inc.)
Slide 4: Idronoxil: active ingredient in NOX66
Idronoxil: active ingredient in NOX66 HO O ▪ Idronoxil is an isoflavonoid resulting from a med chem program seeking a tumour-specific inhibitor of sphingosine kinase; based on the plant hormone, genistein OH ▪ Primary biological functions (eg. tumour cell cytotoxicity) believed to be associated with
Slide 5: Idronoxil – putative pathway
Idronoxil – putative pathway1-4 1. Idronoxil binds to ENOX2, leading to inhibition of the trans membrane proton pump, which in turn leads to an accumulation of protons (H+) within the plasma membrane. 2. Combination of accumulation of protons + direct effect inhibition blocks sphingosine kinase acti
Slide 6: Rationale: combination idronoxil + radiotherapy
Rationale: combination idronoxil + radiotherapy ▪ Idronoxil inhibits DNA repair mechanisms: ▪ down-regulates PI3 kinase/Akt pathways ▪ inhibits topoisomerases 1 and 2; degrades PARP-1 ▪ Idronoxil increases ceramide levels: ▪ Increased plasma membrane ceramide levels known to enhance radiation damage
Slide 7: Radio-sensitisation with idronoxil in lung and prostate cancer cell lines
Radio-sensitisation with idronoxil in human lung (A549) and prostate (PC-3) cancer cell lines Data on File
Slide 8: Idronoxil: heritage clinical development (Chemo)
Idronoxil: heritage clinical development (Chemo) ▪ Phase 1a, 1b, 2a, 2b and 3 studies conducted between 1999 and 2009 using idronoxil (phenoxodiol) oral and intravenous (cyclodextrin) formulations ▪ Late Phase development focus on restoration of sensitivity to carboplatin in platinum- refractory ova
Slide 9: Rationale for NOX66
Rationale for NOX66 NOX66 was developed as a means of minimising Phase 2 metabolism. ❖ Suppository dosage formulation chosen based on: ▪ lack of transferase activity in human rectal mucosa ▪ avoidance of first-pass liver metabolism ❖ NOX66 formulated in fatty acid base – rat data showing: ▪ Remains
Slide 10: Rat PK studies
Rat PK studies Intravenous Rectal PK Parameters (co-solvent) (NOX66) Dose (mg/kg) 3.5 35 Cmax (ng/mL) 4647 ± 315 62.3 ± 8.7 Tmax (h) - 0.12 ± 0.04 AUC0-30 (ng.h/mL) 8129 ± 166 1187 ± 389 Half-life (h) 0.32 ± 0.07 9.6, 6.1 Clearance (mL/min/kg) 71.9 ± 1.5 - VDβ (L/kg) 2.00 ± 0.40 - Bioavailability 10
Slide 11: Case Study #1 - CRPC
Case Study #1 - CRPC Year of birth 1945 - 2008 Diagnosis ◦ Locally advanced T3 prostate cancer ◦ PSA 60, Gleason Score 9 ◦ Brachytherapy and External Beam radiotherapy ◦ Biochemical relapse soon after, androgen deprivation therapy commenced (intermittent) - 2013 April Developed metastatic disease ◦
Slide 12: Case Study #1
Case Study #1 Oct 2014: Palliative RT approach for pain management ◦ 30Gy, 10 fractions ◦ Plan for further follow up RT if required ◦ NOX66 self administered prior to, during and immediately after RT 7/7/14 29/9/14 28/11/14 2/3/15 30/4/15 Total PSA 140 170 ? ? ? ◦ Given his PSA response, what is the
Slide 13: NOXOPHARM
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Slide 14: Radiotherapy planning screen
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Slide 15: Radiotherapy planning screen
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Slide 16: Case Study #1
Case Study #1 Oct 2014: Palliative RT approach for pain management ◦ 30Gy, 10 fractions ◦ Plan for further follow up RT if required ◦ NOX66 self administered prior to, during and immediately after RT 7/7/14 29/9/14 28/11/14 2/3/15 30/4/15 Total PSA 140 170 13 0.18 0.07 PSA <0.01 for 3 years Main sid
Slide 17: NOX66 Development plan
NOX66 Development plan Chemotherapy: ◦ Phase 1 Study ongoing – monotherapy and combination with Carboplatin ◦ Interim Data: Positive Safety Profile, efficacy signals supporting further investigation ◦ Study to complete in Q2 2018 ◦ Phase 2 Studies planned to commence in Q2 2019 External Beam Radioth
Slide 18: NOX66-002A Study (DARRT-1)
NOX66-002A Study (DARRT-1) First study investigating the combination NOX66 with radiotherapy Hypothesis for radiotherapy program: NOX66 will complement the effect of palliative radiotherapy and as such ◦ Sensitize the direct radiotherapy effect, providing a greater response to treatment within the i
Slide 19: Objectives
Objectives Primary Secondaries Exploratory • Safety and tolerance of • Investigate if NOX66 will • Levels of ceramide, S1P, NOX66 in escalating dose sensitize tumours to ENOX2 in blood – look for cohorts, in combination palliative radiation correlation with palliative therapy • miRNA – early radioth
Slide 20: Key Inclusion Criteria and Dosing
Key Inclusion Criteria and Dosing Key Inclusion Criteria ▪ Histologically confirmed prostate cancer or PSA of >100 ng/mL at original diagnosis ▪ Metastatic disease evidenced by either CT/MRI imaging or bone scan ▪ Objective evidence of disease progression ▪ Eligible to receive palliative radiation t
Slide 21: Participating Sites
Participating Sites Australia - In collaboration with TROG: Genesis Cancer Care Newcastle, NSW Radiation Oncology Centre, Gold Coast University Hospital, QLD Genesis Cancer Care Mater Hospital, NSW Central West Cancer Care Centre – Orange Health Service, NSW North West Cancer Centre, Tamworth Hospit
Slide 22: Case Study #2 – Rare Cancer
Case Study #2 – Rare Cancer ▪ Female, Year of birth 1947 ▪ Aug 2016: Diagnosis ▪ Metastatic leiomyosarcoma of retroperitoneum / IVC ▪ Metastases in Lung ▪ Second primary sigmoid adenocarcinoma in-situ ▪ Persistent cough (for 3 months) ▪ No curative treatment options available – palliative therapy (d
Slide 23: Case Study #2
Case Study #2 ▪ June 2018 ▪ Completed 5 x 21-day cycles NOX66 / doxorubicin (60mg/kg) ▪ NOX66 was 400mg for cycles 1-3, increased to 800mg cycles 4-5 ▪ NOX66 for Days 1-7, doxorubicin on day 2 ▪ AEs = Skin reaction (perineum) considered due to doxorubicin ▪ Scans during chemo showed little change in
Slide 24: Primary: - Irradiated
Aug 2016 (diagnosis) Jun 2017 (post chemo, prior to RT) Primary: - Irradiated Sept 2017 (1 month post RT) Nov 2017 (3 month post RT)
Slide 25: Lung Mets: - Non-Irradiated
Aug 2016 (diagnosis) Jun 2017 (post chemo, prior to RT) Lung Mets : - Non-Irradiated Sept 2017 (1 month post RT) Nov 2017 (3 month post RT)
Slide 26: Case Study #2
Case Study #2 Summary of RT and Scan: ▪ RT From 15th-28th June; NOX66 from 14th June-5th July ▪ CT 4th Aug, follow up review 6th Sept: ▪ Adverse Event = fatigue during and post RT – considered RT related ▪ Asymptomatic; cough resolved during RT and not recurred (patient reported) ▪ Primary tumour un
Slide 27: NOX66 RT Plans 2018-19
NOX66 RT Plans 2018-19 Q1 2018 Q2 2018 Q3 2018 Q4 2018 Q1 2019 NOX66-002A (DARRT-1): Phase 1; CRPC Interim Interim Study Analysis Analysis Report Safety NOX66-006 (DARRT-5): Phase 2a; All Cancers Safety, 12 week scans NOX66-003 (DARRT-2): Phase 2/3; CRPC Lu-PiN – Phase 1, Investigator Led, Lu-PSMA +
Slide 28: Thank You
Thank You Contact for more information: Noxopharm Limited PO Box 824 Turramurra NSW 2074 Phone - +61 2 9144 2223 Email – [email protected]