SixOne Solutions is developing small molecule drugs targeting the Eya/Six1 cancer pathway for treating breast cancer and other cancers. The Eya/Six1 pathway was discovered to play a central role in breast cancer growth and metastasis by SixOne's scientific founders. SixOne has identified compounds that disrupt the Eya/Six1 protein complex in two ways, and these compounds have shown efficacy in breast cancer cell assays. SixOne aims to optimize these lead compounds, demonstrate efficacy in animal models of breast cancer, and attract a strategic partner to complete clinical development and commercialization.

1. Ginny Orndorff, CEO
www.sixonesolutions.com
ginny.orndorff@gmail.com

2.  SixOne Solutions LLC is an early-stage preclinical
company developing targeted small-molecule
breast cancer drugs.
 We are pursuing a streamlined, cost-effective
development plan for first in class products that
address a cancer pathway not addressed by any
current cancer drugs.
 The compounds we are developing may be
broad-spectrum cancer drugs, as the pathway
targeted by our compounds is implicated in many
hard-to-treat cancers.

3.  Scientific founders
Prof. Heide Ford and Assoc. Prof. Rui Zhao
◦ Discovered new cancer pathway
◦ Comprehensively validated a key pathway protein complex
as a drug discovery target
 Target validation subsequently confirmed by others
 Key review paper:
http://informahealthcare.com/doi/abs/10.1517/14728222.2014.978860
◦ Through a 10-year collaboration determined the target
structure, developed assays, and identified small molecule
compounds that disrupt this target protein complex
 SixOne is commercially developing these compounds
to treat breast cancer and potentially other cancers.

4.  Breast cancer is the second leading cause of
cancer death for women (after lung cancer)
 Each year 450,000 women die of breast cancer
globally.
 Metastasis (spread of cancer to other organs) is
the primary cause of death.
 Critical market need: new therapies to prevent or
treat metastasis.
 Breast cancer treatment = $10 B global market
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5. SixOne
drugs
Radiation/chem
otherapy
Herceptin (targeted
therapy)*
Targeted to
cancer cells
Yes No
(debilitating
side effects)
Target found in
normal cells but
higher amount in
cancer cells
Prevent or treat
metastases
Yes Yes- but soon
recur
Yes – but soon recur
Triple-negative
patients
Yes Yes -but soon
relapse
No
% Patients 50% + All – but soon
relapse
25%
*Leading targeted therapy on the market today with $1.8 B in
annual sales

6. SixOne Solutions is developing first in class small molecule products
for treating metastatic breast cancer.
• Our products address Eya/Six, not targeted by current cancer drugs.
• The central role of Eya/Six1 in breast cancer, and, importantly, in
metastasis, was discovered by our scientific founder Dr. Heide Ford.
• The Eya/Six1-controlled cancer pathway is found in a majority of
breast cancer patients and 90% of metastatic breast tumors
• Eya/Six1 has been shown to turn on genes leading to metastasis
(spread) of cancer cells from the original breast tumor, thus drugs
targeting Eya/Six1are expected to block cancer growth and
metastasis.
• SixOne’s drugs are expected cause few side effects because they will
be specific to Eya/Six1, which is present in cancer cells but
generally not found in normal cells. Non-toxic drugs are critical as
breast cancer treatment is expected to shift to combinations of
targeted drugs in place of chemotherapy.

7. Eya Six1
Proliferation
Survival
Invasion
Migration
Proliferation
Survival
Invasion
Migration
Tumors
Metastasis
Eya/Six1 complex may be a key control point in a widespread
cancer pathway; they have been implicated in breast, ovarian,
lung, pancreatic, brain, and other cancers.
The proteins Eya and Six1, abundant during embryo growth, are
generally absent in adult cells. When aberrantly active in adult
cells, their usual functions result in tumor growth and metastasis.

8. Six1 gene manipulation also inhibits growth/metastasis of other
cancers in mouse models:
- Rhabdomyosarcoma (Yu et al., Nat Med 2004)
- Hepatocellular Carcinoma Ng et al., Int J Cancer (2010)
- Kidney cancers (Imam et al., Oncogene 2010)
- Colorectal Cancer (Li et al., Int J Clin Exp Path 2014)
The impact of Six1 has been established in mouse models:
Manipulation of Six1 genes in mice dramatically decreases
tumor growth and metastasis.

9. Six1 does not act alone: metastasis increases and
survival decreases in mouse models when Six1
binds with Eya
Six1/Eya
Six1 mutants not
able to bind to Eya
Six1 mutants not
able to bind to Eya
Six1/Eya
Tumor growth and
metastasis
Survival

10. Target Validation: Human patients
High Six1 + high Eya2 levels in human breast cancer
patients = poor prognosis
Farabaugh et al, Oncogene, 2012

11. SIX1 EYA1 References
Wilms’ Tumor Wilms’ Tumor Li et al., Am J Pathol 2002; Imam et al., Oncogene, 2010
Acute Leukemia Acute Leukemia Wang et al., Blood, 2011
Glioma Glioma Auvergne et al., Cell Reports, 2013
Breast Cancer Breast Cancer Pandey et al., Oncogene 2010; Farabaugh et al., Oncogene
2012
SIX1 EYA2
Ovarian Cancer Ovarian Cancer Zhang et al., Cancer Res, 2005; Behbakht et al., Cancer Res,
2007
Lung Cancer Lung Cancer Huang et al., J Clin Oncol, 2009; Mimae et al., Clin Cancer
Res, 2012
Cervical Cancer Cervical Cancer Wan et al., Int J Cancer, 2008; Bierkens et al., Genes
Chromosomes Cancer, 2013
Breast Cancer Breast Cancer Pandey, Oncogene 2010; Farabaugh et al., Oncogene, 2012;
Patrick et al, Nature SMB 2013
SIX1 EYA3
Ewing Sarcoma Ewing Sarcoma Robin et al., Mol Cancer Res, 2012 and unpublished data
Breast Cancer Breast Cancer McCoy et al., J Clin Invest 2009; Micalizzi et al., J Clin
Invest 2009; Pandey et al., Oncogene 2010

13. We identified small molecule compounds that disrupt
the Eya/Six1 complex by two different modes: Group
1 compounds inhibit a key catalytic function of Eya.
Group 2 compounds prevent Eya and Six1 from
binding to form the active complex.

14. 14
Group 1 compounds
Inhibit Eya catalytic
activity (uM) through an
allosteric mechanism
Group 2 compounds
And block tumor
cell motility – a
hallmark of cancer

15. Issued and Pending Patent Applications:
• Protein complex target
• Methods of treatment
• Proprietary small molecule compounds

16.  Optimize compounds for greater potency
◦ Straightforward medicinal chemistry to improve
compounds and select best compound to commercialize
 Demonstrate efficacy in animal disease models
◦ Standard industry accepted breast cancer mouse models
Upon successful completion of these milestones,
we believe we will be able to attract a strategic
partner who will complete clinical development
and launch products.

17. RESEARCH/CLINICAL DEVELOPMENT MILESTONES
ACCOMPLISHED TO BE COMPLETED
2004-
2012
2013 2014 2015 2016 2017
TARGET
DISCOVERY/VALIDATION
DRUG DISCOVERY
MEDICINAL
CHEMISTRY/OPTIMIZATIO
N
IN VIVO EFFICACY
FINANCING: Funding to date Funding requirements
Pre-founding grants
Non-dilutive grants
Investment (current raise)
$1.0M $0.5M $0.5M
$340K
$800K
Once efficacy
demonstrated in
mouse model -
potential EXIT to
strategic partner

18.  Ginny Orndorff, CEO
◦ Founder/CEO of Evolutionary Genomics.
◦ Previously with GenoPlex, NeXstar, and Genex.
 Scientific Founders actively involved
◦ Dr. Heide Ford and Dr. Rui Zhao, CU Denver AMC
 Dr. Xicheng Sun, Chemistry Consultant
◦ 3D Partners, N30, Replidyne, Array Biopharma
 Dr. Cathy McCall, Regulatory Consultant
◦ Clinipace Boulder
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19.  Novel, well-validated target for breast cancer and
potentially a broad range of cancers.
 Compounds targeting this pathway are expected to
be effective in metastatic breast cancer and have
low toxicity.
 Compounds in hand have demonstrated efficacy in
standard human breast cancer cell assays.
 Clear medicinal chemistry optimization path.
 Pioneering IP portfolio including issued patent.
 Shareholder exit through merger/sale to strategic
partner possible in approximately 18 – 24 months.
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