Applied Protein Sciences

simplifying oncology care

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 APS allows aggressive and efficient cancer
treatment by preventing
MUCOSITIS,
a debilitating side effect of radiation and
chemotherapy

“[Preventing mucositis] could allow patients to remain on chemotherapy longer. It is well

keeping patients on chemotherapy

established that

longer increases their survival”

- Dr. Phil Gold, GI Oncologist, Director of Clinical Research, Swedish Hospital Cancer Institute

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Current treatments are inadequate and physicians routinely stop, delay
or reduce chemotherapy and radiation dosage because of Mucositis

Kepivance is the only approved Passive Techniques

drug
Incidence of OM by
type of cancer
“…patients are advised to suck
on ice chips, to cool the oral
cavity and provide relief from
pain”

Narrow application scope

Reduces incidence but does •  Physicians stop cancer treatment

not prevent severe OM •  Underlying cancer rejuvenates

Patients with severe OM may have a 4x mortality risk *

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APS proprietary products AP001/AP002 prevent Mucositis by restoring
cellular integrity through cell proliferation and migration
Healthy Tissue – Long and slender villi
  Undifferentiated cells from the crypt zone divide,
differentiate, and migrate to the luminal surface
  Continuous exfoliation of cells at the crypt is
counterbalanced by proliferation in the crypt so
that the epithelium mass is stabilized

Cisplatin treatment causes severe mucosal

injury or MUCOSITIS
  Necrotic villi
  Disfigured crypts and irregular crypt heights
  Loss of cellular integrity at the tips of crypts
(shown by arrows)

cisplatin + AP002
AP002 treatment prior to Cisplatin prevents
epithelium breakdown
  Competitively binds to EGFr to prevent
expression of NF-kB; Inhibits TNF-α, IL-1β, and
IL-6
  Abundance of goblet and absorptive cells are
seen that preserve mucosal integrity
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AP002 is a cytoprotective drug that plays a prophylactic role to inhibit
the progression of both oral and GI mucositis
Healthy mucosa Initiation and Signal Amplification and
Healing
prior to RT/CT primary damage response Ulceration

Day 0 Day 6 Day 12 Day 18

Proposed Mechanism of Action of AP002 to prevent the progression of mucositis

Simultaneously, AP002 AP002 can prevent

AP002 prevents severe
When administered prior acts as a cyto-protective moderate and severe
ulceration; inhibits
to RT/CT, AP002 agent; reduces DNA mucositis; providing a
pathways for mucosal
induces cell proliferation damage and apoptosis; faster recovery period
breakdown and
and migration, increases Prevents mast-cell and eliminating
stabilizes the epithelial
epithelial thickness degranulation; reduces expensive
cells
levels of IL1β and TNF-α hospitalization costs

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APS Product Pipeline – 12 Month Projections
Therapeutic Area
Pre Clinical Phase I Phase II Phase III

Head and Neck

Oral
Mucositis
Solid Tumors

Oesophagal
GI
Mucositis
Gastro Intestinal

Proctitis
Inflammatory
Diseases
IBD

IND NDA
Present status 12 month projections
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APS Team is well experienced along all the stages of the drug
development process
•  Aman Johar, MBA, CEO
–  Swartz Fellow for Entrepreneurship, Carnegie Mellon

•  Dr. Marna Doucette, PhD, FDA & Regulatory Affairs

–  24+ years of industry experience in oncology and supportive care
–  Experience with 7 INDs, 3 NDAs and 5 Phase 3 compounds

•  Dr. Shelley Ching, PhD, MBA, Non-Clinical Development and Toxicology

–  Member-Scientific Advisory Board, CPDD, UNC & Bill and Melinda Gates
Foundation

•  Maynard Lichty, Product Development

–  30+ years experience with pharmaceuticals

•  Dr. Steve Sonis, Scientific Adviser

–  Chief, Division of Oral Medicine, Harvard Medical School
–  Intimately involved with Kepivance clinical trials

•  Dr. Rik Derynck, Scientific Adviser

–  Director, Institute of Regenerative Medicine, UC-San Franscisco
–  Pioneering team member at Genentech
–  20+ years of direct experience with APS product platform and recombinant DNA
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APS – Biomodels Partnership in the News

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APS provides excellent partnership opportunity and is poised for growth
in large, multiple markets with unmet medical needs
•  APS products can be “standard of care” for prevention of Oral and
GI Mucositis
–  Prevention of Oral Mucositis can save $2B+ in hospital costs
–  Platform can be rapidly expanded to include therapeutic products for
Proctitis and IBD

•  Validating pre-clinical studies

–  Multiple planned products for multiple Oral and GI indications

•  6 issued US patents
–  A worldwide patent portfolio covers APS technology

•  Excellent technical and development team

–  Strong clinical and drug development track record
–  Strategic partnerships to foster innovation

•  APS is interested in co-development and commercialization

opportunities for its drug candidates for Oral and GI Mucositis,
Proctitis and IBD
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