Late stage development of two first-in-category wound care products - Stockholm, November 2019
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Late stage development of
two first-in-category wound
care products
Stockholm, November 2019
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2
Management Team
Jonas Ekblom, CEO Jenni Björnulfson, CFO
▪ Over 25 years of experience from the life science ▪ More than 20 years of experience from the financial
sector, with a focus in pharmacology and drug markets with a strong focus on the health care sector.
development. ▪ Experience from Handelsbanken Markets, Alfred
▪ Experience from Bows Pharmaceuticals AG, Pharmacia, Berg/ABN AMRO, S&P, ABG Sundal Collier, GHP
Biovitrum, Sequenom and Invitrogen ▪ Joined 2016
▪ Ekblom has published over 60 peer-reviewed articles
▪ Joined 2010
Margit Mahlapuu, CSO Ulrika Wennberg, COO
▪ Close to 20 years of experience in discovery and ▪ Over 20 years of business experience as an
development of novel pharmaceuticals from the biotech entrepreneur, project manager, management consultant
and pharma industry. and business leader.
▪ Experience from Arexis, AstraZeneca, Biovitrum ▪ Experience from Axelar, Jederström, Accenture
▪ Authored 50 articles in peer-reviewed scientific journals ▪ Joined 2009
and inventor on 7 pending patent applications.Professor
in Molecular Medicine at Sahlgrenska Academy
▪ Joined 2007
3
Promore Pharma in Brief
▪ Two late stage, first-in-category products
▪ Human peptides for local administration with extraordinary safety
Phase III – PXL01 Phase IIb – LL-37
▪ Preventing adhesions after tendon ▪ Treating chronic wounds, mainly
repair surgery VLUs
▪ No prescription drugs ▪ No prescription drugs
▪ 1 million patients in EU, NA & JP ▪ 6 million patients in EU, NA & JP
▪ Addressable EU market 300 MUSD ▪ Addressable global market 3 BUSD
▪ Indication broadening opportunities ▪ Indication broadening opportunities
Vision To solve the global problems of scarring, adhesions and
chronic wounds
4
Company Background
2003 - 2010 2010 - 2016 2017 -
PXL Technology
2005; Gothenburg
• Merged under Pergamum in 2010 • Two late stage clinical programs
• ~ 20 programs
LL-37 Technology • Cost-effective organization
• ~ 30 employees
2003; Stockholm • No in-house laboratories
• Part of the Karolinska • Network of high-quality
Development group until 2015 CROs and CMOs
DPK-060 Technology • Listed on Nasdaq First North
2004; Lund Growth Market since 2017
Omniohealer
BioCis Pharma Herantis Pharma shares
5
Peptides: A Unique Class of Therapeutics
Chemistry
Biology
Peptides present a combination
of advantages compared to the
most common drug classes
Molecular weight (Da)
102 103 104 105 106
6
Local Delivery of Peptides: The Way to Go
BIOAVAILABILITY
Drug available at site of action in a medically
relevant amount
DURATION
Temporal exposure can readily be controlled
through choice of formulation
DOSING
Flexible dosing by choice of injection volume
SAFETY
Rapid degradation of peptides in the
bloodstream: very low systemic exposure
7Trauma Has the Third Largest Spend
60
patients in the world, will contract a
hard-to-heal wound, a dermal scar or Wounds, trauma and amputations
a complication due to a post-surgical account for the third largest area of
million adhesion every year healthcare spending in the world
CNS Cardiovascular Trauma Oncology
>600 600 400 300
USD billion1) USD billion1) USD billion1) USD billion1)
18% 15% 10% 27%
of clinical studies2) of clinical studies2) of clinical studies2) of clinical studies2)
1) World Health Organization (WHO) 2018
2) Clinicaltrials.gov; an estimate of number of planned and ongoing clinical studies 8PXL01
Adhesions and Scars
Adhesions Promore Pharma and PXL01
Dermal scarring, following plastic surgery
▪ Derivative of naturally occurring peptide
or burn wounds/trauma
(lactoferricin)
– Unique anti-inflammatory action: prevents
fibroblastic adhesions without interfering with
Tendon repair Thyroid wound healing
surgery surgery – Pro-fibrinolytic properties
▪ First indication: Prevention of adhesions after
Numerous abdominal tendon repair surgery (hand, arm and foot)
surgical procedures,
e.g. colorectal cancer ▪ Other indications
Spinal surgery, – Prevention of fibrosis in conjunction with spinal
including DDD surgery (corporate partnership)
– Clinical feasibility testing of PXL01 in dermal
Total knee scar prevention
arthroplasty
Adhesions form after almost any type of surgery and are a significant cause of post-surgical complications
▪ Cause need for secondary surgery
▪ Constitute considerable burden on healthcare systems
10Tendon Injuries: The Medical Need
The medical need Criteria for effective clinical documentation
▪ Annual incidence of accidental tendon injuries ▪ High incidence of scar formation
corresponds to 0.1% in the general population ▪ Methods for clinical assessment are:
– procedures in the hand account for one third – Validated
– Quantitative
▪ 20–50% of subjects undergoing surgery of tendons
of the hand never recover full mobility and finger – Standardized
strength post-surgery ▪ Mainly young and healthy patients
▪ There are currently no pharmaceutically active ▪ Surgery in a limited number of specialized centers
products on the market for anti-adhesion
In 2015, U2’s singer had a
bicycle accident with a
hand injury resulting in
impaired ability to play
guitar
Nerve damage
Tendon transections are often accompanied by nerve
damage resulting in pain or sensory loss
11PXL01: Product Concept
Single-injection of lubricating hyaluronate-based gel containing PXL01
PRE-FILLED SYRINGE
Sterile solution, 0.5 ml with stability of >12m
DOSING
Single administration at the surgery
BIOAVAILABILITY
Drug available at site of action
SAFETY
Rapid degradation of peptides in the
bloodstream: very low systemic exposure
12A Large Phase IIb Trial is Completed
Study Basics PHSU02
• 138 patients with accidental transection of flexor tendon in zone II of the hand
• One single administration in conjunction with surgery of PXL01 in HA vs. placebo (saline) (1:1)
• Efficacy and safety followed until 12 months post-surgery
• Study centers in Sweden, Denmark and Germany
Randomization End of Trial
Administration
(Active or Placebo)
Trial Product
Post-Operative Assessment Visits
Visit 1 Visit 2 Visit 3 Visit 4 Visit 5 Visit 6 Visit 7 Follow up Follow up
Day 0 1-5 days 2w 4w 6w 8w 12 w visit 1 visit 2
(Screen, post surgery 6 months 12 months
Surgery)
13A Large Phase IIb Trial Completed
Endpoint PXL01 Placebo P-Value Comments
Mobility in injured finger
Primary endpoint Phase III
DIPAM (the most distal finger joint) 6 months 60 degrees 41 degrees PPhase III Study planned in EU
Study Basics PHSU03
▪ ~600 patients with accidental transection of flexor tendon in zone II of the hand
▪ Single administration in conjunction with surgery of PXL01 (two doses) vs. placebo (saline) (1:1:1)
▪ Efficacy and safety followed until 12 months post-surgery
▪ Study centers in Sweden, Germany, Poland, Italy and India
Administration Randomization 420 Patients Completing Protocol End of Trial
Trial Product (Active or Placebo)
Post-Operative Assessment Visits
Visit 1 Visit 2 Visit 3 Visit 4 Visit 5 Visit 6 Visit 7 Follow up Follow up
Day 0 1-5 days 2w 4w 6w 8w 12 w visit 1 visit 2
(Screen, post 6 months 12 months
Surgery) surgery
Planned to initiate patient enrolment in H1 2020
15Comparing Phase III Costs and Success Rates
Lower Phase III costs for PXL01 program Musculoskeletal show with higher success rates
Phase III cost, USDm1) Success rate in Phase III, %2)
52 70
65
57 55
Musculoskeletal
40
24 25
17
11
Promore Endocrine Oncology CVD CNS Promore Endocrine CNS CVD Oncology
High cost-effectiveness in late stage development
1) Martinez, 2016 Driving Drug Innovation and Market Access: Part 1-Clinical Trial Cost Breakdown
2) BIO 2016, Clinical Development Success Rates 2006-2015 16Addressable Market of more than USD 600m
Pricing assumptions Addressable market
▪ Tendon Repair Surgery costs approx. USD 10,000 (in Europe North America
some cases up to USD 14,000)
▪ Tenolysis costs approx. USD 14,000 Population 370m1) 335m
– Recommended in 30% of cases
– Variable compliance (6% - 20% of patients) to
undergo secondary surgery Incidence rate 0.1% 0.1%
▪ PXL01 can reduce tenolysis by 65%
▪ Full direct economic benefit 20% x 65% x USD
14,000 = USD 1,800 Number of patients 370k 335k
▪ 50% of full benefit reasonable price according to Curo
Ltd, i.e. USD 900
▪ Assumed price range USD 800 – USD 1,200 Price (USD) 800 1,000
Addressable market
296m 335m
(USD)
1) Europe based on top five largest markets, Benelux and the Nordics
17Opportunities to Expand PXL01 Market
>1 million
procedures globally
1-2 million
procedures globally
>40 million
relevant procedures
Tendon and
nerve injury
repair Degenerative
Disc Disease
(Partnership with PRP)
Dermal
Scarring
PXL01 in hyaluronic acid
Potential for expansion of geographies and indications is strong
18LL-37
LL-37: Treatment of Chronic Wounds
Medical Need and Costs for Society Promore Pharma and LL-37
▪ >15 million patients with challenging ▪ Naturally occurring peptide (cathelicidin)
wounds on the major pharmaceutical – Antimicrobial
markets
– Angiogenic
– Stimulates keratinocyte migration
VLUs
DFUs ▪ LL-37 involved in wound biology
Pus ▪ Present in acute wounds but not in chronic
Other
wounds
▪ First indication VLUs
▪ Largest patient population in major
▪ Very few prescription products pharmaceutical markets
▪ Some available for DFUs, but all with ▪ No pharmaceuticals available
limited medical value ▪ Not as complicated from a development
▪ Low R&D competition perspective
▪ Costs for treating chronic wounds exceed ▪ All chronic wounds could potentially be
10,000 USD per episode addressed with LL-37
20LL-37: Product Concept
A viscous hydrogel containing the peptide is applied 2-3 times weekly in conjunction with regular dressing changes
▪ Does not require change of medical practice
▪ Application frequency matches current medical
standards
▪ Can be applied by patient or a nurse
▪ Excipients are well characterized and can be procured
at a very low cost
Dosing
Flexible dosing by choice of injection volume
Compatibility
Can readily be combined with the most common
compression bandages
Film
The hydrogel forms a thin local ”film” over the wound area
21A Phase IIa Trial is Completed
Study Basics
▪ 34 patients (completing protocol)
▪ 3 week treatments run-in on placebo (blue line); followed by treatment with active or placebo for 1 month (application
every 3:d day (totally 8 doses)
▪ 4 arms with 8-9 subjects in each: 3 doses of LL-37 versus placebo
Day -30 Day -21 Day 0 Day 30 Day 60
Screening Run-In Randomization End-of-Treatment End of study
WA WA WA WA
The subjects were randomized to four groups Criteria for Evaluation
▪ Placebo (N=9) ▪ Adverse events
▪ LL-37 0.5 mg/mL (N=8) ▪ Local reactions
▪ LL-37 1.6 mg/mL (N=9) ▪ Immunological reactions
▪ LL-37 3.2 mg/mL (N=8) ▪ Estimated healing rate
▪ Wound area
22LL-37 Efficacy: Wound Area Reduction (%)
Optimal dose range for Phase IIb identified
Wound Area Reduction (%)
Randomization
Percentage of baseline wound area
120
120 Placebo
LL-37 (0.5 mg/ml) Optimal dose
100
100
LL-37 (1.6 mg/ml) interval identified
LL-37 (3.2 mg/ml) (RP2D)
80
80
▪ Two doses of LL-37 demonstrated
60
60
unambiguous efficacy, including healing rate
and wound area reduction
40
40
* pHEAL LL-37: Ongoing Phase IIb Trial in VLUs
Study basics
▪ Recruiting 120 patients (completing protocol) in 2 countries (Sweden, Poland)
▪ 3 week run-in on placebo; followed by treatment with active or placebo for 3 months (application 2 times per week); 4
months follow-up
▪ 3 arms with 40 subjects in each: 2 doses of LL-37 vs. placebo
Day -30 Day -21 Day 0 3M 7M
Screening Run-In Randomization Last Dose End of Study
Time points for digital wound area assessment
The subjects are randomized to three groups Criteria for evaluation
▪ Placebo (N=40) ▪ Fraction of patients reaching 50%, 70% and 100% healing
▪ LL-37 0.5 mg/mL (N=40) ▪ Relative wound area reduction and healing rate
▪ LL-37 1.6 mg/mL (N=40) ▪ Multiple safety and tolerability endpoints
50% of the patients recruited in June 2019 – readout expected in 2020
24Addressable Market of USD 3bn
Assumptions Addressable market
▪ European population is larger for LL-37 compared to Europe North America
PXL01
– Assumption includes traditional pharmaceutical Population 470m2) 335m
markets
▪ Incidence difficult to estimate
– Many undetected cases Prevalence rate 0.3% 0.3%
▪ Prices based on an average Regranex treatment
episode (for DFUs)
Treatments per year 1,410k 1,005k
Price (USD) 1,200 1,400
Addressable market
1,692m 1,407m
(USD)
1) Waycaster CR et al, (2016) J Am Podiatr Med Assoc 106: 273-282.
2) Assumption includes traditional pharmaceutical markets in the European Union 25Opportunities to Expand LL-37 Market
>6 million1)
patients
>9 million2)
patients
Venous leg
ulcers (VLU)
(NA, EU, JP)
Diabetic Foot
Ulcers (DFU)*
(NA, EU, JP, CN, IN)
LL-37 in PVA
Potential for expansion of indications is strong
1) Xie T, et al, (2018) Burns Traum 6:18
2) Zhang et al, (2016) Ann. Med. 49:1-21 26Corporate
Business Strategy
Take PXL01 to market in EU Partnering LL-37
▪ Phase III program (PHSU03) being prepared ▪ Phase IIb (LL-37 HEAL) ongoing in EU
in EU and India ▪ Target timeline for completion of the
▪ Market Authorization and Commercialization Phase IIb clinical trial is 2020
▪ Develop PXL01 all the way to market in ▪ After completion, Promore Pharma will seek
EU one or several partnerships with multi-
▪ Either commercialize first indication national companies for confirmatory trials and
independently in EU or through MA
partnerships ▪ Potential for indication broadening to other
▪ Seeking partnerships for both other territories common types of hard-to-heal wounds
(ex-EU) and indications
28Company Milestones
2019 2020
✓
50% of patients Last-patient-last- Clinical study
enrolled in HEAL dose HEAL LL-37 report HEAL LL-37
✓
Ongoing Rights
CTA approval for First-patient-in
Issue
PHSU03 in EU PHSU03 trial
Finalize PXL01 supply chain
29Use of Proceeds in Ongoing Rights Issue
Transaction overview
▪ Issue size: SEK 75m in gross proceeds (net proceeds of SEK 63m) if fully subscribed
▪ Subscription undertakings from existing shareholders of 47 percent of rights issue
▪ Rights issue is guaranteed up to 80 percent from external guarantors
Use of proceeds
Use Amount, SEKm
1 Phase IIb study (HEAL) for LL-37 ~20
2 Preparations for the planned phase III study (PHSU03) for PXL01 ~15
3 IP-related expenses ~5
4 General corporate expenses ~23
Total ~63
30Executive Summary
Late stage clinical development project with extraordinary safety
1
Late stage clinical development phase
2
Unmet medical need – no pharmaceutical products
3
Validated technology with strong IP protection
4
Strong safety profile and low development costs
5
High growth potential – high growth market segment and additional indications
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