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Investor Presentation Dr. Marie Roskrow, CEO & Managing Director
September 2014
ASX: PAB
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Safe Harbour Statement
This presentation contains forward-looking statements that are subject to risks
and uncertainties. Such statements involve known and unknown risks that may
cause the actual results, performance or achievements of Patrys Limited to be
materially different from the statements in this presentation.
Actual results could differ materially depending on factors such as the
availability of resources, the results of clinical studies, the timing and effects of
regulatory actions, the strength of competition and the effectiveness of the
Company's patent protection.
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Highlights of 2014
3rd Quarter (July – September):
o Released details of the planned PAT-SM6 & carfilzomib Phase Ib/IIa clinical trial due to
start end of 2014
o Reported significant progress on all preclinical programmes
o Progressed the GMP manufacturing of PAT-SM6
2nd Quarter (April – June):
o Reported the granting of a third US patent for PAT-SM6
o Released clinical data showing that a patient with end-stage multiple myeloma
responded positively to treatment with PAT-SM6 in combination with other marketed
drugs
o Reported the first plant-based production of PAT-SM6
1st Quarter (January to March):
o Reported final data from successful Phase I/IIa PAT-SM6 single-agent clinical trial
o Rights issue completed: Total fundraising of $7.7 million
o PAT-SC1 10yr follow-up clinical trial data in patients with gastric cancer published
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Corporate Overview
CURRENT YEAR SHARE PERFORMANCE
ASX Code PAB
Share price $0.021
52 week high $0.092
52 week low $0.021
Shares on issue 697,060,986
Market capitalisation $14.6m
Cash @ 30/6/14 $8.6m
Funding Since Listing $54m
KEY STATS & FINANCIALS – 17 SEPT. 2014 (AUD$)
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Marie Roskrow, BSc
(Hons), MBBS, PhD
Managing Director, CEO
Roger McPherson,
CPA, GAICD
CFO, Company Secretary
Frank Hensel, PhD Vice President R&D
John Read, BSc
(Hons), MBA, FAICD
Non-Executive Chairman
Mike Stork, BBA Non-Executive Director
Suzy Jones
Non-Executive Director
MANAGEMENT & BOARD
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Pipeline
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Product
(Target)
Discovery Phase I Preclinical
PAT-SM6 (GRP78)
PAT-LM1 (NONO)
PAT-SC1 (CD55)
PAT-SM6 (GRP78)
PAT-SM3
PAT-SM4
PAT-H12
Phase I
Completed
Phase I/IIa
Completed 2013
Phase I/IIa
Completed
Out- Licensing
Candidate
Phase 2a
Melanoma
Multiple Myeloma Single Agent
Solid Tumours
Gastric Cancer
Multiple Myeloma Combination Carfilzomib
PAT-SM6 (GRP78)
Phase Ib/IIa
Commence 2014
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PAT-SM6
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Patrys’ Lead Antibody: PAT-SM6
PAT-SM6:
o IgM isotype, λ-light chain
o Isolated from stomach cancer patient
o Targets tumour specific epitope on GRP78
o Binds also to oxidised LDL and VLDL
Mode of Action:
o Internalisation upon binding of oxidised
LDL & GRP78PAT-SM6
o Internalisation triggers apoptosis
In vivo & In vitro Reactivity:
o Effective in multiple xenograft models
o Expression data show specific expression
in wide range of tumours incl. melanoma
and myeloma
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Multiple Myeloma - Opportunity Multiple Myeloma – Opportunity
o Cancer of the plasma cells in bone marrow. Cells grow out of control and form
tumours in solid bone, cause damage to other organs
o Estimated to be more than 220,000 cases worldwide and incidence increasing
o 5 year survival of ~30%
o Market expected to increase from ≈$8B (2013) to >$15B (2018)
o Market currently dominated by 3 products: • Revlimid (net sales $4.28B 2013)
• Velcade (net sales $3.77B 2013)
• Kyprolis® (carfilzomib) (net sales $272M 2013)
o Several MAbs currently in clinical development but none approved to date. Likely to
be used in combination therapies
o Significant interest in MM from both large pharmaceutical and biotechnology
companies
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Multiple Myeloma – Pathology
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o Abnormal plasma cells (myeloma
cells) secrete lots of “useless”
antibodies (M proteins)
o Myeloma cells crowd out other blood
cells resulting in anaemia,
thrombocytopenia (bleeding) and
leucopenia (infections)
o Abnormal proteins in serum detected
by electrophoresis
o Abnormal proteins (Bence Jones)
detected in urine
Myeloma cells
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Multiple Myeloma – Clinical Presentation
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o Bone disease and hypercalcaemia o Abnormal protein deposits
o Bone marrow failure and infections
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Therapies for Multiple Myeloma
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Proteosome inhibitors
o Bortezomib (Velcade)
o Carfilzomib (Kyprolis)
Immunomodulators (IMIDs)
o Lanalidomide (Revlimid)
o Pomalyst (Pomalidomide)
o Thalidomide
Chemotherapeutics
o Melphalan
o Cisplatin
o Cyclophosphamide
o Doxorubicin
Stem cell transplantation
o Autologous
o Allogeneic
Clinical studies
o Small molecules
o Antibodies, peptides
o Immunotherapeutics
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Daratumumab (Genmab/Janssen Biotech,Phase III)
Elotuzumab (BSM/Abbott, Phase III)
BHQ880 (Novartis, Phase II)
CD138 toxin- conjugated (BT062, Biotest AG, Phase I/IIa)
PAT-SM6* (Patrys, Phase Ib/IIa)
GRP78
Antibodies in all stages of clinical development
MOR 202 (MorphoSys/Celgene, Phase I/IIa)
Antibodies in Clinical Trials for MM
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*Upcoming trial to begin end of 2014 with PAT-SM6 in combination with carfilzomib and dexamethasone
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PAT-SM6 Monotherapy Trial
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o 12 patients treated with 4 doses PAT-SM6 in 4 dose cohorts (0.3mg/kg, 1mg/kg, 3mg/kg and 6mg/kg/dose) evaluated at day +36 (end of trial)
• 10 male, 2 female: median age 71 yrs
• Received average 5 prior lines of therapy
o PAT-SM6 safe in all patients. No dose limiting toxicity (DLT), no related serious adverse events (SAE) and no related adverse event grade ≥ 4
o No evidence of immunogenicity. PK analysis showed half-life of 7 hrs
o PAT-SM6 specifically targets MM cells in vivo and stimulates significant immune responses
o 4/12 patients had stable disease (day +36 post treatment) with a significant reduction in protein M levels in the peripheral blood
o Patients who received prior treatment with proteasome inhibitors responded best to PAT-SM6
o Mean time to next therapy is 51 days (clinically significant). Two patients had stable disease for >130 days post treatment
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Clinical Data
Preliminary Efficacy
4 patients showed stable disease according to the IMWG criteria
42%
13%
114%
1.40%
54%
36.30%
-16%
48% 40%
7% 1%
81%
-40%
-20%
0%
20%
40%
60%
80%
100%
120%
140%
01-001 01-002 01-003 02-001 02-002 02-003 03-001 03-002 03-003 04-001 04-002 04-003
Incre
ase/D
ecre
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M Protein Changes from Baseline (%)
0.3 mg/kg 1 mg/kg 3 mg/kg 6 mg/kg
Stable
disease
Stable
disease
Stable
disease
Stable
disease
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Clinical Data
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PAT-SM6 Isotype Control anti
CD138
Isotype Control
PAT-SM6
PAT-SM6
Isotype Control
anti-ID
CD138
Pre-treatment
Post-treatment
merge
Immunohistochemical staining with PAT-SM6 on paraffin embedded tumour biopsies from MM patients
The positive control (anti-CD138) and PAT-SM6 bound to patient tissues
Flow cytometry on MM patient bone marrow
Cells from MM patients displayed cell surface binding for PAT-SM6 suggestive the target (GRP78) is present on the MM cells
Detection of PAT-SM6 on circulating MM cells
Before and after dosing, patient blood was collected
and circulating MM cells were purified using CD138
magnetic beads. PAT-SM6 binding was confirmed
using an anti-idiotype antibody specific for PAT-
SM6 (anti-ID) by confocal microscopy. In the post-
treatment sample, red stained MM cells indicate the
presence of PAT-SM6. CD138 was used as a
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PAT-SM6 & Carfilzomib Combination Trial
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Endpoints:
o Primary: The safety and tolerability of PAT-SM6, given in combination with carfilzomib and
dexamethasone in patients with multiple myeloma who are refractory and/or intolerant to
bortezomib, a currently-marketed proteasome inhibitor
o Secondary: Overall response rate, duration of response, time to progression and a series of well-
established assays will measure immunological and disease parameters
Design:
o Single-arm study with a 2-stage design: after treating 9 pts in the 1st stage, if > 2 respond (a partial
response or better), the trial will continue to the 2nd stage and a total of 24 pts will be treated
o Each pt will be treated with up to 4 cycles of PAT-SM6 (6 mg/kg/dose) + carfilzomib (20-27 mg/m2)
+ dexamethasone (40 mg)
o Each cycle will consist of 3 doses of PAT-SM6, 6 doses of carfilzomib and 4 doses of
dexamethasone administered over one month
Timelines:
o Trial projected to start end of 2014 at 2 clinical centres in Germany (Würzburg & Dresden)
o Progressive recruitment of up to 24 pts estimated to take 15-18 months. Data from first 9 patients
will be released
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PER.C6® Cell Line:
o Patrys uses PER.C6® human cell line for GMP production:
Only human cell line commercially available
Over 6300 patients have been treated with PER.C6® products – safe profile
PER.C6® cell line has received regulatory approval in all major markets
PER.C6® derived products have not yet gained marketed approval: Currently in Phase III
Capable of producing high yields of both IgM and IgG antibodies. Cost of goods similar to CHO system
Chinese Hamster Ovary (CHO) Cell Line:
o CHO is a commonly used cell non-human cell line:
CHO is more familiar to big Pharma / Biotech companies
Numerous antibody therapeutics produced in CHO are on the market
Patrys has initiated a feasibility study with CHO cells in order to deliver multiple options to
potential partners
Cell Lines Used in Manufacturing Antibodies F
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PAT-LM1
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PAT-LM1 Antibody & Target
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PAT-LM1:
o IgM isotype, λ-light chain
o Isolated from a lung cancer patient
o Targets tumour-specific epitope of surface-
expressed NONO (non-POU-domain-containing
octomer binding protein)
Mode of Action:
o NONO mainly found in nucleus: involved in
transcriptional & post-transcriptional gene regulation
o Unknown mechanism-of-transport to cell membrane
In Vivo & In Vitro Reactivity:
o Effective in several xenograft models
o Expression data show specific expression in a wide
range of tumors incl. lung, pancreas, colon,
leukaemias
Crystal structure of NONO with PSPC1
Passon et al PNAS 2012
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PAT-LM1 Preclinical Data
Lung Squamous Cell Carcinoma
Colon Adenocarcinoma
+ control - control PAT-LM1
Esophagus Squamous Cell Carcinoma
Breast DuctalAdenocarcinoma
PAT-LM1 binds C1q, suggestive of CDC IHC staining with PAT-LM1 on tumour tissues
PAT-LM1 reduced
tumour volume &
induced cell-death
Apoptotic cells
Regression
Necrosis
Control tumor LM-1 treated tumor
Cyto-
keratin
H&E
B) Histology on excised tumoursA) Individual (symbols) and mean (bar) tumor volume
(200µg)
(n=10 per group)
Control tumor PAT-LM1 treated tumor
Cyto-keratin
H&E
OD
655
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
20μg 10μg 5μg 1μg 0.5μg
LM1
without C1q coating
with 5μ/ml C1q coating
Apoptotic cells
Regression
Necrosis
Control tumor LM-1 treated tumor
Cyto-
keratin
H&E
B) Histology on excised tumoursA) Individual (symbols) and mean (bar) tumor volume
(200µg)
(n=10 per group)
Control tumor PAT-LM1 treated tumor
Cyto-keratin
H&E
Lung cancer xenograft
0
100
200
300
400
500
600
700
Saline IgM PAT-LM1
Tum
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PAT-SC1
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PAT-SC1 (Gastric Cancer)
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PAT-SC1:
o Pentameric IgM isotype, λ-light chain
o Isolated from a stomach cancer patient
o Targets isoform of CD55 (Decay Accelerating Factor) expressed on surface of multiple
types of cancer cells
POC Trial Results:
o Phase I/IIa (POC) open-label trial conducted 1997-2001 (Germany)
o Safe in 51 pts receiving single 20 mg dose PAT-SC1
o Significant 10 year survival benefit for 30 pts with minimal residual disease (R0) post-
surgery vs. untreated pts (historic control)
Current Stage/Competition:
o Currently in out-licensing process
o Conversion from hybridoma to recombinant PER.C6® cell line completed
o Orphan designation by the FDA for use in gastric cancer
o No other know clinical products targeting CD55
Intellectual Property:
o Key patent granted in various jurisdictions
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2014 Key Milestones
Key Milestone Projected Timing
(CY)
PAT-SM6: o Final data from monotherapy MM trial
o Complete GMP manufacturing for combination MM trial
o Commence combination Phase Ib/IIa MM trial
o Preclinical and clinical data published
1Q, 2014
2H, 2014
4Q, 2014
4Q, 2014
PAT-LM1: o Complete manufacturing process development ready for scale-up
o Preclinical data published
2H, 2014
2H, 2014
PAT-SC1: o Preclinical & clinical trial (gastric cancer) data published
o Out-licensing deal
1Q, 2014
2014
Discovery Abs: o Target work on PAT-SM3, PAT-SM4, PAT-H12
2014
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For Further Information
Contact Details:
Dr. Marie Roskrow, Chief Executive Officer / Managing Director
Mr. Roger McPherson, Chief Financial Officer
Ph: +61 3 9670 3273
Email: [email protected]
Website: www.patrys.com
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