Summary

2011

Founded 2010 in Houston

Vision: To be the leader in the development of metronomic therapies for cancer

$4.2M Series A: Founded by seasoned biotech, pharma and generics executives

Initial indications prioritized for fast clinical & regulatory path (later expansion to wider markets)

About

Strategic Focus

Repurposed drugs with less regulatory, safety and efficacy risk

Cancer treatment with a better quality of life

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of childhood cancers

Childhood Neuroblastoma (neuronal tumors)

average progression-free survival

of pediatric cancerdeaths in U.S.

long-term survival

7%–10%

<5%

15%

42 days

HIGH RISK RELAPSED / REFRACTORY (60% of TOTAL)

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A Critical Unmet Need

Low Survival Even withDose Intensity

Dose Intensity survival by ~ 4x (26%)

Need new agents with non- overlapping toxicities to chemo

Translations of the American Clinical and Climatological Association, vol. 121, page 183, 2010

Change in Death Rate

1969 1979 1989 1999 2009

Neuroblastoma

Acute Lymphoblastic Leukemia

1960 2011NO SIGNIFICANT PROGRESS IN 50 YEARS

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Neuroblastoma Progress Lags Behind Other Childhood Cancers

HighRisk

Initial Treatment: Chemotherapy, surgery, double autologous BMT,

radiation, retinoic acid +/- antibody therapy

1st relapse treatment:

Cytoxan +topotecan therapy

Survival:<5%

Intermediate Risk

Chemotherapy

Carboplatin, Etoposide, Cytoxan, Doxorubicin

Survival:80%–90%

LowRisk

Surgery & Observation

Survival: >90%

Current Treatment

40% 20% 40%

60% relapse<1 year

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O

C=N

H

O2

NN

S

CH

3

O O

Established Drug Profile: Approved for Chagas in South

American and Central American countries starting in 1972

>1000s of patients treated >40 years

MNX-100

Repurposed Drugs:A Successful Strategy

Approved Drug

LeverageNew Clinical

Activity

Strong Clinical & preclinical data

Patent applications filed

Exclusive worldwide rights

Rapid, Lower-Risk Development:• Well understood pharmacologically• Not in US formulary (never approved)• Good toxicology, pharmacology,

carcinogenicity and teratogenicity publications

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Discovery (2002): MNX-100

Rationale for initiating Phase I clinical trial

Metastatic neuroblastoma

& Chagas disease

Cytoxan & topotecan

PLUSMNX-100

6 additional relapsing and

refractory neuroblastoma

patients

Initial Tumor

Necrosis

MNX-100 3 wks

MNX-100 8 wks

MNX-100 12 wks

Necrosis

REMISSION

2 PR’s

4 SD’s

J Pediatr Hematol Oncol 28: 10, 693-6, October 2006

Preclinical Studies: Summary

Directly slows tumor growth in a variety of tumor typesActive in a variety of neuroblastoma and medulloblastoma cell lines (including TICs) and mouse models of neuroblastoma and medulloblastoma

Interacts with catecholamines to enhance toxicitySelective for neuroblastoma and possibly small cell cancer, adrenal cancer, glioblastoma, melanoma, stellate pancreatic, pheochromocytoma, adrenal carcinoma, etc.

Results in Oxidative StressNitroreduction and damage to nucleus

Induces ApoptosisInduction of caspase 3

Suppresses AKT phosphorylationAn important mediator of tumor resistance

Increases tumor response in combination with cytoxan, topotecan and rapamycin• Drug classes widely used across many human tumors, including NSCLC, breast, colon,

ovarian, renal, glioblastoma, CHOP, etc.• Synergistic activity with rapamycin opens door to additional ‘maintenance’ schedules

TumorGrowth

Neuro-endocrine

OxidativeStress

Apoptosis

AKT-P

Synergy

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Phase I Clinical Trial Results

MNX-100:✓activity as single agent✓ efficacy as combination

therapy✓ mild toxicity✓ oral administration

9.1 months PFS

Mean PFS:• Maximum tolerated dose reached: 30 mg/kg/day

• Dose-limiting toxicities were reversible nausea and neuropathy; no hematological or cardiac side effects

• Tumor responses seen both as single agent and in combination

• 6/14 alive 12 months following treatment; greatly improved quality of life including reduced narcotic use, improved mobility, return to school

Phase I Summary of Responses

RECIST Criteria PR SD PDNifurtimox alone   6 (43%) 8(57%)Nifurtimox/cyclo/topo 3 (30%) 5 (50%) 2 (20%)

 Clinical response*      Nifurtimox alone 2 of 5 of SD    Nifurtimox/cyclo/topo 3 of 5 of SD    

*Defined as patients who had radiological stable disease with either a 50% decrease in urinary catecholamines if elevated at study entry, clearance of bone marrow disease on greater than 2 biopsies, or resolution of MIBG activity

PR+SD=80% J Pediatr Hematol Oncol 33:1, 23-30, January 2011

MNX-100 Phase II: Response to Date

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Phase II Response to Date

Response NFX alone 1,2 NFX + CTX + Topo

PR(RECIST)

2/17(12%) 7/29 (24%)

PFS=206 days

SD 5/17 (29%) 13/29 (45%)

PFS= 123 days

PD 10/17 (59%) 9/29 (31%)

PFS=55 days

Multiple relapsed, chemotherapy-

refractory patients

PR+400%

+5 months

SD+224%

+2.2 months

1 19/20 actively progressing at time of study2 patients treated with two 21 day cycles of NFX alone

PFS Increase

PR+SD=70%

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Phase II Responses: Prestudy vs. Treatment

11

NFX Alone NFX + CTX + TOPO

NFX + CTX + TOPO

Follow-on multicenter Phase II studies of MNX-100 shows promising clinical activity in relapsing and refractory neuroblastoma, especially when combined with cytoxan and topotecan• RECIST response rate of 20-30%• PFS in responding patients 4X’s that of nonresponders• Average PFS for all 43 patients (PD, PR, SD) = 154 days• Accrual rate average 0.23 patients/center/month; top centers at 0.5 to 0.6

Combined therapy has acceptable safety profile

Preclinical data suggests AKT and GSH may be important targets• Synergy as well as activity in other cancer cell lines, particularly neuroendocrine (e.g., SCLC)

Next step is to undertake randomized study with appropriate power to prove activity for accelerated approval registration (1992 –314 subpart H) Applies in the setting of a new drug for a serious or life-threatening illness Study may use a surrogate endpoint, reasonably likely to predict clinical benefit (PFS, RR) Show meaningful therapeutic benefit over existing therapy or improved patient response over

available therapy Magnitude and consistency of effect important

MNX-100: Summary

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THANK YOU

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