VAL-083: Validated DNA-targeting Agent for Underserved Cancer Patients September 2018
Forward-Looking Statements Any statements contained in this presentation that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995 and Canadian securities laws. Any forward-looking statements contained herein or made in the course of the presentation are based on current expectations, but are subject to a number of risks and uncertainties. The factors that could cause actual future results to differ materially from current expectations include, but are not limited to, risks and uncertainties relating to the Company's ability to develop, market and sell products based on its technology; the expected benefits and efficacy of the Company's products and technology; the availability of substantial additional funding for the Company to continue its operations and to conduct research and development, clinical studies and future product commercialization; and, the Company's business, research, product development, regulatory approval, marketing and distribution plans and strategies. These and other factors are identified and described in more detail in our filings with the SEC and the British Columbia Securities Commission, including our current reports on Form 8- K s, Form 10-Q s and most recent Form 10-K. We do not undertake to update these forward-looking statements made by us. 2
Corporate Overview & Recent Developments VAL-083: DNA-targeting agent with well-established mechanism of action (MOA) for multiple solid tumor indications Leveraging estimated $90M+ of prior investment by NCI: ~40 PH 1 and PH 2 clinical trials and preclinical studies in multiple indications >1,000 patient safety database Lead indication: Recurrent glioblastoma multiforme (rgbm) leverages biomarker for an underserved patient population Benefitting from accelerated enrollment in both our two PH 2 clinical studies potential to allow for earlier trial completion Strengthened our Board of Directors with world class scientific pedigree through the addition of Dr. Napoleone Ferrara Oppenheimer & Co. Inc. appointed as strategic advisor December 2017 FDA Fast Track Designation for VAL-083 in rgbm Orphan drug designations for glioma, medulloblastoma and ovarian cancer in U.S. and glioma in E.U. 3
Development Strategy for Optimizing VAL-083's Potential Focus on oncology indications for patients with limited alternatives Unique mechanism of action, and biomarker driven studies reduce development risk, cost, and timelines Updated September 2017 NCCN guidelines: Great opportunity for VAL-083 in MGMT-unmethylated GBM Validated standard-of-care biomarker (MGMT promoter methylation) for treatment of GBM Phase 2 second-line GBM study ongoing at MD Anderson Phase 2 front-line GBM international study ongoing at Sun Yat-sen University 505(b)2 strategy allows DelMar to use previous NCI data to support FDA filings Future pipeline opportunities in ovarian and other solid tumor cancers 4
Expanding Pipeline Preclinical IND Phase I Phase II Phase III 2nd Line MGMT-unmethylated GBM VAL- 083 1st Line MGMT-unmethylated GBM Platinum-Resistant Ovarian Cancer Other Solid Tumors Efficient use of shareholder capital to date $34.3M spent to establish clinical programs in multiple indications (as of June 30, 2018) 5
VAL-083: A Validated Precision DNA-targeting Agent 6
Only DNA-Targeting Agents Have Demonstrated Survival Benefit in GBM Interventions with proven therapeutic benefit in GBM - Surgery - Radiotherapy - DNA-targeting agents (temozolomide (TMZ); nitrosoureas) VAL-083 is a structurally-unique, brain-penetrating, DNAtargeting agent - Established clinical activity in GBM (NCI studies) - Differentiated mechanism from TMZ and nitrosoureasovercomes tumor-resistance of those agents 7
DNA-Targeting Agents Are Well-Established Anti-Cancer Class of Drugs ANTI-CANCER DRUG temozolomide BCNU/CCNU Peak Annual Sales $1.1 B (2013) ~$100 m (1980s) Platinum-based chemotherapies bendamustine >$1 billion (2000s) $800 m (2014) VAL-083 DNA Target O6-guanine O6-guanine N7-guanine N7-guanine N7-guanine MGMT Dependent Dependent Independent Independent Independent Cross blood-brain barrier? yes yes no no yes p53 Dependent Dependent Dependent Dependent Less dependent Primary indications CNS tumors CNS tumors Solid tumors Hematologic malignancies CNS & Solid Tumors TBD VAL-083 is a first-in-class DNA-targeting agent with the potential to overcome drug-resistance >60% of GBM patients are MGMT-unmethylated, not responsive to TMZ VAL-083 targeting of N7 of guanine on DNA to overcome MGMT-mediated TMZ resistance (O6 monofunctional DNA alkylation) Established activity in platinum-resistant cancer cell lines (ovarian and NSCLC) 8
GBM Patients Have Very Limited Treatment Options Across All Disease Stages GBM Treatment Paradigm MGMT methylation is a wellestablished, validated biomarker for gauging TMZ efficacy mos < 15mo <40% pts MGMT-methylated mos = 21.7mo >60% pts MGMTunmethylated mos ~ 12.7mo No impact on survival 19.6% ORR, DOR 3.9mo MGMT-unmethylated represents >60% of patients who do not benefit from TMZ treatment resulting in: Treatment-related side effects Increased cost of treatment Source: : Hegi et al. 2005, N Eng J Med 9
MGMT Methylation Status Correlates With GBM Patient Survival Outcomes <40% GBM pts >60% GBM pts Hegi et al NEJM, 2005 MGMT methylation status is correlated with GBM patient survival outcomes TMZ + radiotherapy provides no survival benefit to MGMT-unmethylated GBM compared to radiotherapy alone - Evidenced by September 2017 NCCN guidelines update Source: : Hegi et al. 2005, N Eng J Med 10
Biomarker Testing For MGMT Promoters and Recent NCCN Guidelines Evaluating MGMT promotor methylation: - Has increasingly become standard-of-care in GBM diagnosis - Impacts treatment practice and outcomes September 2017 NCCN guidelines KPS 60: Clinical benefit from temozolomide is likely to be lower in patients whose tumors lack MGMT promoter methylation KPS<60: temozolomide monotherapy is only recommended if tumor is MGMT promoter methylated MGMT testing is a validated and commercially available diagnostic 11
GBM: Initial Opportunity Focusing on MGMT Status Most common and aggressive adult brain tumor with annual incidence estimated at 3-5 per 100,000 adults = ~29,000 new cases in US and EU each year Percentage of newly diagnosed GBM patients (est.) MGMT-Methylated MGMT-Unmethylated 40% 60% > $1 billion annually Treatable patient population (est.) U.S. E.U. Percentage of recurrent GBM patients (est.) 5,104 6,400 7,656 9,600 25% 75% $200-500 million Treatable patient population (est.) U.S. E.U. Market Size 1,914 2,400 5,742 7,200 Source: CBTRUS report 2017; Hegi et al. 2005, N Eng J Med; Brandes et al. 2009, J Clin Onc. 12
VAL-083 is Equipotent Independent of MGMT Promoter Methylation Status U251 MGMT-Methylated GBM Cell line T98G MGMT-Unmethylated GBM Cell line GBM Cell Line U251 (MGMT-methylated) T98G (MGMT-unmethylated) MGMT Expression LOW High TMZ* IC 50 = 22.7μM >>100μM TMZ resistant VAL-083 IC 50 = 2.5μM 2.5μM VAL-083 sensitive *The IC50 values for TMZ are created based on inadequate dose-response curves, as the tested cell lines were moderately or fully resistant to TMZ. Source: Hu et al, AACR 2012 13
Opportunity for VAL-083 in MGMT-Unmethylated Patients In 2 nd Line and Newly Diagnosed GBM Currently Enrolling: Two Phase 2 clinical trials designed to capitalize on robust VAL-083 scientific and clinical data and recently revised NCCN guidelines Recurrent GBM - MD Anderson: Study of VAL-083 in Patients With MGMT-Unmethylated, Avastin-naive Recurrent Glioblastoma (NCT02717962) Newly Diagnosed GBM - International trial: VAL-083 and Radiotherapy in Patients With Newly Diagnosed GBM Having Unmethylated MGMT Expression (NCT03050736) 14
Phase 2 Trial: Avastin-Naïve Second-Line GBM Patients With MGMT-Unmethylated Tumors : Study enrollment ongoing Validate VAL-083 in 2nd-line Avastin-naïve GBM patients post temozolomide failure (N=48) Single arm, MGMT methylation biomarker-driven open label study Primary Endpoint: Overall Survival - The lomustine arm of EORTC26101 trial is the reference control (mos= 7.1 mo) 15
VAL-083 Phase 2 trial In Avastin-Naïve Second-Line GBM Patients With MGMT-Unmethylated Tumors As of September 21, 2018 40 of a planned 48 patients enrolled Enrollment is ahead of original projections Assuming recent enrollment rates continue, we forecast full enrollment by end of 2018 Per protocol design, we anticipate median overall survival to be reached approximately three months after final patient is enrolled 16
Expanded Opportunity For VAL-083 In MGMT- Unmethylated Newly Diagnosed (Front-Line) GBM Updated NCCN guidelines highlight opportunity for VAL-083 - VAL-083 equipotent independent of MGMT methylation NCI studies demonstrate survival benefit of VAL-083 + radiotherapy vs. radiotherapy alone MGMT-unmethylated GBM: >60% of all newly diagnosed patients = ~17,000 patients annually in US and EU VAL-083 Phase 2 study in 30 newly diagnosed MGMTunmethylated GBM - Sun Yat-sen University Cancer Center (Guangzhou, China) - Open label trial for temozolomide-naïve GBM patients 17
VAL-083 Phase 2 Trial in MGMT-Unmethylated For Newly Diagnosed (Front-Line) GBM Precedent-setting Biomarker Aided Patient Selection Validate activity of VAL-083 plus radiation in newly diagnosed MGMTunmethylated GBM patients compared to historical control (N=30) Primary Endpoint: Progression free survival (PFS) Compare with MGMT-unmethylated in historical control PFS=5.3m Secondary Endpoint: Overall survival (OS) Source: Hegi et al. 2005, N Eng J Med 18
VAL-083 Phase 2 trial In Newly Diagnosed GBM Patients With MGMT-Unmethylated Tumors As of September 21, 2018 Study Update 9 patients enrolled at Dose-escalation stage 3 patients started dosing at 40mg/m 2 19
VAL-083 Reduces GBM tumor Progression in vivo, after Bevacizumab induced Hypoxia Study conducted by Luxemburg Institute of Health 20
VAL-083: Opportunity in Platinum-Resistant Ovarian Cancer Ranked 5th in female cancer death worldwide Incidence: Est. 11-13 per 100,000 women= ~66,000 new cases in US and EU annually Median survival Pt-resistant ovarian cancer with currently available therapies <12 months Newly diagnosed ovarian cancer patients (est.) Patient PopulationUS Patient PopulationEU 22,400 44,149 Recurrence rate Platinum-Resistant ovarian cancer patients (est.) Est. over $3 billion in 2022 62% 13,888 Market Size 27,367 Source: EUCAN, NCI-SEER, Birrer 2014, Am Soc Clin Oncol Educ Book, Ethier 2017, Gyne. Can. Evaluate Pharma 21
Advisory Committee for Ovarian Cancer Established a highly capable ovarian cancer advisory board Dr. Bradley Monk Dr. Maurie Markman Dr. Thomas Herzog Arizona Oncology (US Oncology Network) Cancer Treatment Centers of America University of Cincinnati Cancer Institute Seek to combine with PARP inhibitors for platinum-resistant ovarian cancer, a highly unmet medical need Initiate Phase 1/2 trial when a suitable design, and sufficient capital to complete the trial is secured 22
Financial Position Condensed Balance Sheet Data As of June 30, 2018 Cash $6.0 million Total liabilities $1.6 million Total stockholders equity $5.4 million Condensed Statement of Cash Flow Data Cash used in operating activities Fully Diluted, As-Converted Shares Year Ended June 30, 2018 $9.9 million 43.3 million 23
Upcoming CY 2018 Milestones Clinical Data Update for both PH 2 ongoing trials: Targeted for Peer-reviewed Scientific Conference SNO (November 2018) Open label studies allows for intermediate publication of results Financials First Quarter FY 2019 (November 2018) 24
Investment Summary VAL-083: Structurally unique and differentiated activity DNA-targeting agent Unique potential to circumvent MGMT-related temozolomide-resistance in the treatment of GBM Leverages MGMT biomarker per September 2017 NCCN guidelines Represents >60% of GBM patients Multiple opportunities validated by numerous late stage clinical studies VAL-083 s Orphan Drug Designation in GBM and ovarian cancer Ovarian cancer is no longer eligible for orphan drug designation given its prevalence of >200,000 in the U.S. Prudent management focused on efficient use of shareholder capital Strengthened Board of Directors and management team 25