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Targeted Delivery of Therapies
OTCQB: ACXA
Company Presentation – January 2017
Statements made in this presentation that are not historical facts are forward-looking
statements that involve risks and uncertainties. The inclusion of forward-looking statements,
including those related to the ability of the Company to perform per its license agreements
with UCSF and Accelerating Combination Therapies LLC and meet its obligations; the ability
of the Company to successfully develop and commercialize its BranchPoint device and ACX-
31 program, and execute its business plan; the business strategy, plans, and objectives of
the Company; and any other statements of non-historical information should not be regarded
as a representation that any of our plans will be achieved. Actual results may differ materially
from those described in this presentation due to the risks and uncertainties inherent in our
business, including, without limitation, risks and uncertainties related to: our research and
development efforts, including pre-clinical and clinical testing; regulation by the FDA and
other government agencies; the timing of regulatory applications and product launches; our
ability to successfully commercialize our products; and other risks detailed in our filings with
the Securities and Exchange Commission filings, including our most recent Annual Report on
Form 10-K and our most recent Quarterly Report on Form 10-Q.
You are cautioned not to place undue reliance on these forward-looking statements, which
speak only as of the date hereof. We undertake no obligation to revise or update this
presentation to reflect events or circumstances that occur after the date of this presentation.
Forward-Looking Statements
2
• Accurexa is a development-stage biotechnology company focused on the targeted delivery of therapies
• Diversified development pipeline:
� ACX-31 local chemotherapy wafer developed for the treatment of brain cancer in collaboration with Johns Hopkins University
� Combination of ACX-31 wafer with a PARP inhibitor in development (AstraZeneca’s and Clovis Oncology’s PARP inhibitors approved)
� Collaboration with DelMar Pharmaceuticals to develop ACX-31 wafer in combination with DelMar’s VAL-083 small molecule chemotherapeutic
UCSF: University of California, San Francisco(1) Glial Derived Neurotrophic Factor
Investment Highlights
3
� Collaboration with UCSF to deliver stem cell-derived GDNF(1) for treatment of Parkinson’s Disease using Accurexa’s BranchPoint delivery device
• Virtual product development team with integrated Bioengineering, Formulation, Manufacturing, Quality Control, Regulatory capabilities
Pipeline – Targeted Delivery of Therapies
4
ACX-31
Pre-Clinical Clinical
Pre-IND Meeting
Phase 1 Phase 2 Phase 3
ACX-31 + Val-083 Combination
BranchPointParkinson’s Stem Cell Treatment
Pre-IND Meeting
ACX-31 + PARPiCombination
ACX -31implantable local chemotherapy
wafer to treat brain tumors
5
• Glioblastoma Multiforme (GBM) is one of the most aggressive brain cancer types
� ~ 22,000 patients are newly diagnosed with GBM and 15,000 deaths each year in the US
• Accurexa licensed patent for local delivery of temozolomide and BCNU from Dr. Brem(inventor of Gliadel®) at Johns Hopkins University
• Both oral temozolomide and local BCNU are FDA approved for the treatment of GBM
• Oral temozolomide generated US sales of $420 million and global sales of $910 million under its brand name Temodar® in 2012, before it became generic
6
ACX-31 Local Chemotherapy Wafer
Source: Evaluate Ltd., Transparency Market Research, National Cancer Institute
First-line treatment: Temozolomide
• Marketed as Temodar by Merck
• US sales of $420 million and global sales of $910 million before generic entry in 2012
• FDA approved based on improvement of survival by 2.5 months
Gliadel (local BCNU implants)
• Implantable chemotherapy wafers
• Global sales of ~$30-40m
• FDA approved based on improvement of survival by 2.3 months
Avastin
• Marketed by Roche
• Global sales of ~$120 million
• FDA approved based on an improvement in progression free survival but Avastin did not improve overall survival in later studies
Current Standard of Care for Glioblastoma
7
Local delivery covered by
ACX-31 Patent
ACX-31 Potential Market Opportunity
8
Glioblastoma Treatment Global Sales ($ million)
historic and projected
Source: Evaluate Ltd., Transparency Market Research
ACX-31 Potential Market Opportunity
0
200
400
600
800
1000
1200
1400
2012 2013 2014 2015 2016 2017 2018 2019 2020
Potential Market Opportunity created by generic sales erosion of Temodar
Temodar
AvastinGliadel
Current Standard of Care Improves Survival by Months
9Source: UpToDate; Gil-Salu, J., Neurocirugia, 2004; Walker, M., J. Neurosurgery, 1978; Westphal, M., Neuro-Oncology, 2003; Stupp, R., NEJM, 2005; Athanassiou, H., JCO, 2005; Stewart, L., Lancet, 2002; Lai, A., JCO, 2011.
Median Survival (Months) by Therapy
0
2
4
6
8
10
12
14
16
18
Radiation Therapy (RT) RT + Oral Temozolomide RT + Local BCNU
Cost per treatment
Unmet Needs:
• Survival limited by delivery of effective chemotherapy dose to tumor site
• Oral temozolomidelimited by blood-brain-barrier
~$30-40,000(branded pricing)
~$30,000
ACX-31 Could Improve Survival Significantly
10
Median Survival (Days)
• ACX-31’s local delivery of chemotherapy significantly improved survival by 45-90% in comparison to oral delivery in a rat study at Johns Hopkins University
• ACX-31 gradually releases chemotherapy over 4 weeks
0
5
10
15
20
25
30
35
40
45
Control Oral TMZ Local TMZ Local TMZ +
BCNUTMZ: Temozolomide
P=0.001 over oral
P<0.0001 over oral
Advantages of ACX-31’s local
delivery of chemotherapy
• Direct delivery of drug to tumor site
• Achieve effective drug concentration
• Limit systemic side effects
• Reduced frequency of dosage
ACX-31 Development Pathway Confirmed with FDA
11
FDA pre-IND Meeting:
• 505(b)(2) pathway confirmed with one Phase 2 trial followed by one Phase 3 trial
• Non-clinical studies adequate except for one 2-week GLP toxicology large animal study
• Phase 2 to be conducted in patients with recurrent glioblastoma
ACX -31
in combination with PARP inhibitor
12
• PARP (Poly ADP Ribose Polymerase) is a family of proteins that can repair the DNA damage to cancer cells caused by the chemotherapy drug temozolomide
� Inhibiting PARP can potentially increase the effectiveness of temozolomide in damaging cancer cells
• Olaparib is the first PARP inhibitor approved in December 2014 and marketed by AstraZeneca under its brand name Lynparza
� Lynparza generated $156 million in sales in the first nine months of 2016 and AstraZeneca expects $2 billion in peak sales
• Evidence from scientific studies of the synergistic effects of temozolomide in combination with PARP inhibitors in the treatment of cancer
� Phase 1 OPARATIC clinical trial treating brain cancer patients with olaparib and oral temozolomide (Cancer Research UK)
� Phase 1 clinical trials testing olaparib and oral temzolomide in lung cancer and Ewing’s sarcoma (Massachusetts General Hospital)
13
ACX-31 Local Chemotherapy Wafer
PARP inhibitors approved or in Phase 3 development
14
Clinical
Phase 1 Phase 2 Phase 3
FDA Approval
talazoparib
veliparib
niraparib
ACX -31DelMar Collaboration
15
• Development of ACX-31 wafer for the local delivery of DelMar’s VAL-083 in combination with temozolomide and/or BCNU to treat brain cancer and other solid tumors
• Combination will hit two distinct cytotoxic DNA alkylation targets: O6 and N7 of guanine while minimizing systemic toxicity
• Potential synergy against cancer stem cells already established
• DelMar granted exclusive option to license or acquire products for further development and commecialization
• Potential 505(b)(2) pathway based on existing VAL-083 data and DelMar’s Phase I/II clinical trial of VAL-083 in brain cancer patients
ACX-31 DelMar Collaboration
16
VAL-083 + Temozolomide:Potential Activity against Cancer Stem Cells
17BTIC: Brain Tumor Initiating Cells
A Novel Combination Therapy for Brain Cancer
18
• Leverages Accurexa’s experience with temozolomide + BCNU combination product
� Accurexa had successful pre-IND Meeting with FDA
� Prof. Brem (inventor of GliadelTM) at Johns Hopkins University serves as advisor
• Leverages DelMar’s research regarding VAL-083 mechanism of action
� Activity against MGMT(+) glioblastoma and brain tumor initiating stem cells
� DelMar had successful VAL-083 Phase I/II clinical trial and End-of-Phase II meeting with FDA
BranchPointlocal delivery of brain therapeutics
19
Straight needle — Current standard of care
20
• Delivery with regular syringes with straight needle requires multiple straight penetrations
• Some patients receive up to 16 separate brain penetrations in stem cell trials
Multiple cranial penetration with risks bleeding or stroke
BranchPoint’s curved, flexible catheter delivers therapeutics to multiple target areas with single penetration
Silvestrini, et al, Mol Therapy, 2014 21
BranchPoint delivers therapeutics without reflux or leakages
No reflux or leakage found on using BranchPoint for brain therapeutics
delivery
22
Reflux of at least 75% is observed when the straight, rigid syringe is
used for delivery of brain therapeutics
Source: Silvestrini MT, Yin D, Coppes VG, Mann P, Martin AJ, Larson PS, Starr PA, Gupta N, Panter SS, Desai TA, Lim DA. Radially branched deployment for more efficient cell transplantation at the scale of the human brain. Stereotact Funct Neurosurg. 2013;91(2):92-103.
• BranchPoint allows local delivery of multiple therapeutics, e.g. stem cells, chemotherapy, gene therapy
� Funded with $1.8 million by California’s Stem Cell Agency CIRM
• UCSF Collaboration
� CNS10-NPC are human neural stem cells that express Glial-Derived Neurotrophic Factor (GDNF) for the treatment of Parkinson's Disease
� CNS10-NPC to be delivered by BranchPoint device
BranchPoint Parkinson’s Stem Cell Treatment
23UCSF: University of California, San Francisco
Parkinson’s caused by lack of neurotransmitter dopamine
Team Accurexa – Lean, virtual organization leverages capabilities of collaboration partners
24
George Yu, MDPresident & CEO
Greg MathisonRegulatory & Quality
Assurance
William CallahanBoard Director
Agnes CobbumRegulatory Affairs
Avi DombFormulation,
Manufacturing
Clinical and Scientific Advisors
25
• Dr. Henry Brem, Professor of Neurosurgery and Director of
Neurosurgery Department, Johns Hopkins University – Built one of the
largest brain tumor research and treatment centers in the world. Invented and
developed Gliadel® wafers to locally deliver chemotherapy to brain tumors.
• Dr. Betty Tyler, Associate Professor of Neurosurgery, Johns Hopkins
University – Runs a highly successful laboratory in the field of translational
research. Assisted in preclinical studies that led to bringing Gliadel® to brain
tumor patients as standard of care.
• Dr. Daniel Lim, Associate Professor of Neurological Surgery, UCSF –
Lead inventor of BranchPoint with over 18 years of research experience in
neural stem cell therapies and brain tumors. Co-surgeon in Stem Cells Inc.’s
Phase 1 clinical trial of neural cell transplantation to PMD patients.
Financial Summary
26
• OTCQB Ticker: ACXA
• Common Shares Outstanding: 9,198,954 (as of 11/4/2016)
• Cash: $1,458,126 (as of 9/30/2016)
• $2.25m Equity Financing from Sabby Capital in June 2015
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