Download Xenome Limited

Xenome Limited
May 2011
Xenome highlights
  Private, Australian pain-focused company
  Xen2174: novel therapeutic product for the
management of acute and chronic pain
  Validated norepinephrine transporter (NET)
inhibitor
  Compelling clinical data
  Positive preliminary 16 patient PII data
  Phase 2 POC by 3Q11
  Long term, composition-of-matter patent
  Global product rights
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Company overview
Corporate
history
• Unlisted public company
Locations
• Brisbane (HQ) and San Diego
Platform
• Proprietary libraries of venom peptides and analogs and supporting
peptide chemistry
Lead
compound
• Xen2174
Major
shareholders
• Queensland BioCapital Fund (QBF)
• Founded in 1998 with technology from University of Queensland
• Management of moderate to severe post operative pain
• GBS Venture Partners
• Amylin Investments, LLC
Corporate
Partner
• MedImmune, LLC (a subsidiary of AstraZeneca)
Key
Management
• CEO: Michael Aldridge (Peplin, Bear Stearns)
• VP Clin Dev: Rob Geckeler, MBA (Avera, Arena, Elan, Parexel)
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Venoms as a starting point for drug discovery
  Highly active pharmacological
agents
  Rapid
  Potent
  Injected (in most cases)
  Venom peptides from cone snails
  Generally small (< 20 aas)
  Disulfide bonds provide structure
and stability
  ~60 venom peptides per species
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Postoperative pain: market overview
 
Acute Pain: Duration of 0 to 7 days. The cause may be known or unknown. Acute pain usually
occurs as part of a single and treatable event. Acute pain occurs as a result of traumatic
injury, surgical procedure, or a medical disorder. It is often (not always) associated with
autonomic nervous system responses (tachycardia, hypertension, diaphoresis). Acute pain
decreases with time.1
 
There are ~101 million surgeries performed in the US, Europe and Japan2
 
In 2005, 7.7m orthopedic surgeries in the US, Europe and Japan (3.7m in the US)3. Due to an
aging population and increasing obesity due to sedentary lifestyles, growth in these
procedures is expected to continue
Total US Surgeries 1996 – 2006 Growth6 Knee (Total replacement/ revision of replacement/ repair) 589,0004 Total knee +70% Hip (Total or par@al replacement/ revision of replacement) 504,0004 Total hip +33% Par@al hip +60% Bunionectomy 209,0005 1) 
2) 
3) 
4) 
5) 
6) 
American Pain Society, et al. “Optimizing the treatment of Pain in Patients with Acute Presentation”. 2010.
Datamonitor, DMHC2044, 10/04
Datamonitor Orthopedic Postoperative Pain 2005
American Academy of Orthopaedic Surgeons (data obtained from the National Hospital Discharge Survey)
J Bone Joint Surg Am. 1994;10:1586-1593
National Center for Health Statistics. Health, United States, 2009: With Special Feature on Medical Technology. Hyattsville, MD. 2010.
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Orthopedic postoperative pain treatment regimen
  Current US standards include a multimodal approach specific to patient, type of
surgery, pre-, post- and discharge settings. General pharmacologic guidelines1 are:
  Opioids, NSAIDs, local anesthetics
  Contemporary delivery systems (patient-controlled analgesia over intermittent
dosing via IM, SC) and techniques (neuraxial)
  Post-op pain management is dependent on patient’s overall medical condition
(blood pressure, respiratory status, etc.), level of consciousness, pain level, and
ability to take oral medications.
t = 0, Surgery
In-hospital recovery
t – 48h
Oral NSAIDs
(major joint
replacement) in
major medical
centers
1) 
t – 1h
GA min prior;
RA, LA, IV,
Epidural and/or
IT usually
30-45 min prior
PACU to 24-48h
provide IV, IM or
PCA opioid while
in hospital
Convert to oral
opioid, (may be
in combination)
before discharge
Discharge
Discharge
patient will receive Rx
for oral opioid in
combination w/ NSAID,
Acetaminophen,
Aspirin
Veterans Affairs/Dept of Defense Clinical Practice Guideline for the Management of Post-Operative Pain
GA = Gen. Anesthesia, IV = Intravenous, IT = Intrathecal, LA = Local Anesthetic, OP = Opioid, PACU = Post Anesthesia Care Unit, PCA = Patient-controlled
analgesic, PO = Oral, RA = Regional Anesthetic
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Acute pain treatment options, unmet medical need
Type
Active Ingredients
Key Brands
Opioids
Codeine, Fentanyl,
Hydrocodone, Hydromorphone, Meperidine,
Methadone, Morphine,
Oxycodone, Tramadol
Actiq®, Ultram®,
•  Powerful analgesic
Oxycontin®,
•  Familiarity
Avinza®, Kadian®,
Oramorph®,
Roxanol®,
Fentora®,
Duragesic®,
Lorcet®
•  Respiratory Depression
•  Sedation
•  Nausea, vomiting,
constipation in 30-80% pts
•  Controlled substances
NSAIDs
Acetaminophen,
Aspirin, Celecoxib,
Etodolac, Ibuprofen,
Indomethacin,
Ketorolac, Naproxen,
Piroxicam, Sulindac
Celebrex®,
•  Decrease opioid
Toradol®, Acular®, requirement
Aleve®,
•  Favorable side
Anaprox®,
effect profile
Naprosyn®,
Naprelan®
•  Often not sufficient alone
post-op pain (targets mildmoderate)
•  Increase bleeding time
•  Cardio contraindications
Xyclocaine, ChloroLocal
Anestheti procaine, Bupivacaine,
c
Lidocaine, Prilocaine,
Mepivacaine,
Levobupivacaine,
Ropivacaine
Marcaine®,
Nesacaine®,
Chirocaine®,
Carbocaine®,
Polocaine®,
Naropin®
Benefits
Shortcomings
•  In combination with •  Allergic reaction may occur
OP, may have
•  Not for pts with cardiac,
prolonged duration
hypothyroidism or other
of action
endocrine disease
•  Delivery requires health care
professional
•  Dual mode of
•  Controlled substance (II) with
action
less, but similar opioid side
Unmet medical need: Powerful analgesic
with
effective
•  Efficacy
effects control of
hydrocodone
andand no abuse potential
moderate/severe pain, favorable side effect
profile
oxycodone.
NET/
Opioid
Tapentadol
Nucynta®
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The Xenome solution: Xen 2174
  Novel drug with a validated mechanism of action providing effective and
powerful pain relief
  Single intrathecal administration provides rapid onset of action and
potential for multi-day period of sustained therapeutic benefit
  Favorable side effect profile (as compared to other powerful pain
medications)
  Non-sedating, no hypotension, respiratory depression, GI complications,
tolerance, psychological (addiction) or neurological side effects
  Primary market opportunity is pain following major orthopedic surgery
  Secondary market opportunity is certain forms of intractable chronic pain
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Xen2174 clinical data summary
  Completed multiple clinical studies, with drug administered to ~73 patients in total
  Two phase I volunteer studies (one IV, one IT)
  Two small phase II studies (acute post-surgical pain, chronic cancer pain)
  Key results from phase I/II study in 37 cancer patients with chronic pain
  No DLT at doses up to 30mg
  No consistent trend in AEs, with most mild (56%) or moderate (22%) in severity
  Evidence of efficacy seen at all doses above 0.025 mg
  >90% primary pain relief for at least one patient per cohort
  Preliminary PII (XC0308) 16 patient bunionectomy trial (randomized, double
blind):
  13 patients, single intrathecal administration of Xen2174 (1mg dose), 3 patients placebo
  Consistent response trends seen for all measures including longer time to onset of
moderate-to-severe pain, reduced opiate use in all periods, reduced daily pain scores in
all periods (through Day 12), favorable safety profile
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Indication of acute activity: XC0308 opioid reduction
  Reduction in opiate use ~32% reduction in opiate use over post-op
period through 96 hrs. after surgery
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Indication of acute activity: XC0308 time to onset
  Time to onset of moderate to severe pain: shift to mean 5 hours from
expected onset of 2- 2.5 hrs. following surgery
* Excludes one patient who did not reach moderate-to-severe pain (patient did not require PCA
hydromorphone (Days 1-2 post-op) or Lortab® (Days 3-5 post-op)
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Next step: Proof-of-concept, EU, PII bunionectomy trial
Rationale
  Bunionectomy is validated post-operative pain model
  Certain practices use intrathecal anesthesia
Study
design
  Patients undergoing primary unilateral bunionectomy with
local anesthesia and a sedative
  Placebo-controlled, single-blinded, single intrathecal (IT)
bolus administration of Xen2174
  200 patients in total
  3 doses (50 ea. at 1.0, 1.75, and 2.5 mg) + placebo
Study
objectives
  Co-primary end points
  Reduction in consumption of rescue analgesia
  Time to onset of moderate to severe pain
  Secondary objectives
  Assess safety and tolerability in acute post-operative
pain setting
  Estimate duration of efficacy
  Explore dose-effect relationship
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Major milestones through December 2011
  3Q11: Complete Xen2174 Phase II POC study (XC0409) in postsurgical pain
  3Q11: Complete Xen2174 Drug-Drug interaction study (XC0610)
  1Q12: Meet and resolve concerns with FDA regarding pre-clinical
package
  Ongoing: Execute one or more new discovery partnerships
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Head Office:
L1, 17 Station Road
Indooroopilly ,
Queensland
Australia 4068
ph: +61 7 3720 8055
Fx: +61 7 3720 8388
Xenome Limited
Further information:
Michael Aldridge, Chief Executive Officer
[email protected]
www.xenome.com
Postal Address:
PO Box 1024
Indooroopilly Centre
Queensland
Australia 4068