NuvOx	  Pharma	  Oxygen	  Nanotechnology	  Platform	  –	  Cancer	  and	  Other	  Life	  Threatening	  Conditions	  NuvOx	  Pharma,	  LLC,	  1635	  E.	  18th	  St.,	  Tucson,	  AZ,	  85719	  www.nuvoxpharma.com	  	  Introduction	  NuvOx	  developing	  drugs	  that	  deliver	  oxygen	  to	  hypoxic	  tissue	  to	  treat	  life	  threatening	  conditions	  	  	  Snapshot	  Clinical	  stage	  biopharmaceutical	  company	  Phase	  Ib	  clinical	  trial	  in	  brain	  cancer	  Product	  over	  100x	  more	  eﬀective	  than	  others	  in	  é	  O2	  Preclinical	  data	  in	  multiple	  indications	  Drug	  currently	  produced	  at	  NuvOx	  $7.4M	  raised	  	  $3.1M	  grants;	  	  $4.3M	  equity	  –	  A	  Series	  1&2	  In	  addition	  founders	  contributed	  $1.8M	  Active	  in	  R&D	  partnering	  discussions	  Product	  Development	  Status	  Development	  Status	  Formulation	  components	  have	  been	  modiﬁed	  to	  assure	  a	  patent	  estate	  potential	  as	  a	  barrier	  to	  competition	  Manufacturing	  	  Lab	  Scale	  is	  5-­‐15	  L	  with	  400-­‐1200	  10	  mL	  vials/~$2	  material	  costs	  per	  dose.	  
Stability	  for	  lab	  scale	  batches	  are	  6+	  months	  Process	  development	  and	  optimization	  under	  way	  to	  increase	  stability	  to	  beyond	  1	  year	  Technology	  –	  Description	  Manaufacturing	  Process	  DDFP	  	  mixed	  with	  surfactant	  and	  buﬀered	  aqaueous	  solution	  High	  pressure	  homogenization	  makes	  Nanoemulsion	  	  NVX	  	  2%	  DDFPe	  Emulsion	  Stability	  Data	  Critical Quality Attributes are monitored and displayed below
from over 12 in-house batches.

Oncology	  Indication	  1	  million	  Cancer	  Pa.ents	  per	  year	  in	  US	  treated	  with	  Radia.on	  Therapy	  Hypoxic	  Tumors	  are	  Resistant	  to	  Radia.on	  Therapy	  	  Require	  3x	  higher	  dose	  Cannot	  increase	  the	  dose	  –	  side	  eﬀects	  Results	  in	  incomplete	  tumor	  kill	  and	  tumor	  recurrence.	  	  	  Tumor	  Hypoxia	  is	  Prevalent	  Tissue	  Oxygenation,	  Normal	  Vs	  Tumor,	  	  	  (partial	  presure	  of	  O2	  in	  mm	  of	  Hg)	  60	  50	  40	  30	  20	  10	  0	  Normal	  Tumor	  Reviewed in Vaupel, P. et al., Antioxidants & Redox Signaling, 9: 1221, 2007

Solution	  –	  	  Increase	  Oxygenation	  %	  Survival	  at	  30	  days	  80%	  60%	  40%	  20%	  0%	  pO2 in Tumor Tissue vs. Time.
NVX-108 given at t = 10 mins

No	  Treatment	  RAD	  RAD	  +	  NVX-­‐108	  Complete reversal of radiation resistance in hepatoma and é survival inpancreatic cancer

Phase	  1b	  Started	  in	  Glioblastoma	  Multiforme	  Pre-Radiation Therapy

4 weeks after radiation +TMZ + NVX-108

TOLD	  MRI	  	  Pre–infusion images (top) and post-infusion images (bottom)
TOLD MRI confirms tumor re-oxygenation at 0.17 cc/kg NVX-408

Sample	  curve	  ﬁtting	  for	  tumor	  ROI	  TOLD	  MRI	  Tumor	  T1	  Values	  (ms)	  Set	  #	  Mean	  Std	  1	  (pre)	  1533.3	  82.2	  2	  (post)	  1115.6	  30.9	  3	  (pre)	  1665.3	  196.9	  4	  (post)	  1088.9	  42.5	  Net Present Valuefor Cancer Indications
Tumor	  Type	  Glioblastoma	  Worldwide	  ($M)	  $63	  Lung	  Cancer	  (NSC)	  $1,648	  Other	  Cancers	  Prostate	  Cancer,	  Pancreatic,	  Head	  and	  Neck	  Total	  NPV	  $3,349	  $5,059	  Assumptions: First Product Sales GBM 2018, NSC Lung 2020, OtherCancers 2022 $1,000 per dose, Rindopepimut - $100,000 per patient,
VAL-083 -$67,200 per patient.

Additional	  Indications	  Animal	  Studies	  Show	  Improved	  Outcomes	  in	  Additional	  Indications	  Heart	  Attack	  and	  Stroke	  –	  ~	  80%	  reduction	  in	  tissue	  damage	  Hemorrhagic	  Shock	  –	  100%	  survival	  with	  40%	  blood	  loss	  –	  Air	  Force	  Traumatic	  Brain	  Injury	  -­‐	  Navy	  Sickle	  Cell	  Crisis/Acute	  Chest	  Syndrome	  Clinical	  Status	  In	  this	  Adaptive	  Dose	  Escalation	  phase,	  we	  believe	  we	  are	  the	  MTD	  and	  are	  conﬁrming	  that	  in	  our	  clinical	  trial	  in	  Australia.	  	  	  After	  which	  the	  trial	  design	  calls	  to	  add	  6	  patients	  with	  full	  PK	  workup	  with	  the	  primary	  endpoint	  being	  safety	  and	  secondarily	  6-­‐month	  survival.	  	  	  With	  this	  PK/Safety	  our	  strategy	  is	  to	  ﬁle	  an	  IND	  for	  a	  multi-­‐center	  cancer	  study.	  
If	  no	  signal	  of	  improved	  survival	  we	  will	  consider	  other	  indictions.	  NuvOx Collaborations
Cancer	  U	  of	  A,	  BNI,	  Stanford,	  Monash	  Univ.	  (Aus),	  NCI,	  RTOG,	  Ribomed	  Stroke	  U	  of	  Arkansas,	  U	  of	  A,	  UCLA,	  NINDS	  Heart	  Attack	  U	  of	  A,	  IMCOR	  (Sao	  Paolo,	  BR),	  NHLBI	  Traumatic	  Brain	  Injury	  US	  Navy	  Hemorrhagic	  Shock	  US	  Air	  Force	  Sickle	  Cell	  Univ.	  of	  Pittsburgh,	  NHLBI	  Acute	  Respiratory	  Distress	  Syndrome	  U	  of	  A	  

Decreased	  Stroke	  Brain	  Damage	  by	  85%	  Rabbits - 18F-MISO PET images and brain tissue specimens, topcontrol and bottom NVX-108 treatment

Decreased	  Stroke	  Brain	  Damage	  by	  85%	  % Infarct Volume at 24 Hrs• Repetitive	  IV	  bolus	  doses	  of	  0.1	  cc/kg	  DDFPe	  every	  90	  minutes	  commencing	  1	  hr	  post	  stroke	  onset	  • Rabbits	  euthanized	  24	  hours	  post	  stroke	  onset;	  %	  infarct	  volume	  quantitated	  14N=16123.39% brain infarct

1085% reduction is significant at
p=0.008864

N=90.51%
brain infarct** p=0.008

20No Treatment

0.1 mL/kg DDFPeWoods, S. D., et al. "Progress in Dodecafluoropentane Emulsion as a
Neuroprotective Agent in a Rabbit Stroke Model." Molecular neurobiology 48.2
(2013): 363-367.

100%	  Survival	  in	  Hemorrhagic	  Shock	  963

CO2 production (n=3)
O2 consumption (n=3)

0Time of death

Bone break
060120180

Time (min)240300360

420

12Gas exchange (mL/min*kg)

Blood loss by end of hemorrhage: 27.2 +/- 0.5 mL/kg
Blood loss at The End: 31.1 +/- 0.6 mL/kg

VGas exchange (mL/min*kg)

Hemorrhage

Hemorrhage

96DDFPeV

12

CO2 production (n=4)
O2 consumption (n=4)

3Bone break

Blood loss at end of hemorrhage: 27.5 +/- 0.1 mL/kg
Blood loss at euthanasia: 32.7 +/- 0.4 mL/kg

0060

120

180

Time (min)Pigs - Tyssebotn et. al. Study Final Report to USAMRMC, 2008.

240300360

420Competitive	  Advantages	  Reduced	  Development	  Risk	  Core	  technology	  Approved	  in	  Europe	  as	  an	  ultrasound	  contrast	  agent	  $100	  million	  spent	  by	  licensor	  developing	  core	  technology	  Used	  safely	  in	  2,200	  patients	  5	  patents	  issued,	  5	  pending	  	  12	  years	  exclusivity	  for	  each	  ﬁrst-­‐in-­‐class	  indication	  Collaboration	  Outline	  Partner	  makes	  an	  equity	  investment	  in	  NuvOx	  with	  option	  to	  negotiate	  an	  R&D	  Partnership	  NuvOx	  provides	  relevant	  pre-­‐clinical/clinical	  data	  to	  support	  product	  development	  in	  the	  Region	  Collaboration	  terms	  for	  Development	  NuvOx	  to	  provide	  DDFPe	  for	  evaluation	  and	  clinical	  development	  Exclusive	  commercial	  rights	  for	  the	  Region	  NuvOx	  Pharma	  	  Thank	  You!!	  
NuvOx	  Pharma,	  1635	  E.	  18th	  St.,	  Tucson,	  AZ,	  85719	  	  dwilson@nuvoxpharma.com	  oﬃce:	  520-­‐624-­‐6688	  www.nuvoxpharma.com