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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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