Transcript Acaisia - Acacia Pharma

Company Presentation
November 2010
Dr Julian Gilbert
Introduction
• Acacia Pharma is a focused, cancer supportive care company
– A significant, growing commercial opportunity with high unmet needs
• Experienced management team, track record of value creation
• Investment from Gilde Healthcare Partners & Management
• Generated a clinical pipeline with multiple, near term, value
inflection points, using proprietary in-house R&D “engine”
– High probability of success, based on established drugs
– High value, unmet medical need
• Investment of £6.5 million from Gilde & Management
– Cash through to December 2011 delivering
• Phase I & II for APD515 (xerostomia)
• Phase IIa PoC for APD421 & APD403 (PONV & CINV)
• Phase IIa PoC for APD209 (cancer cachexia)
Team
•
Dr Julian Gilbert – CEO
– Commercial Director & Co-founder, Arakis
• SK&F, BTG, Mundipharma, Chiroscience
•
Dr Robert Gristwood – CSO
– CSO & Co-founder, Arachnova
• Pfizer, SK&F, Almirall, Chiroscience
•
Andrew Muncey – CFO
– CEO, Amura
• Swiss Bank Corp, PwC, Lorantis
•
Dr Gabriel Fox – CMO
– Head, Global Oncology Marketing, Roche
• NeXstar, Gilead
•
Dr Ian Walker – Head of Project Leadership
– Head of Development, Arakis
• Reckitt & Colman, Ethical, Quadrant
Focus
• Acacia Pharma is a hospital focused pharmaceutical company
• Advantages of a hospital focus:
–
–
–
–
Target areas of high unmet medical need
Be competitive (many large pharma focused on primary care)
Develop products through to the marketplace
Retain product rights, thereby value, through own sales
• Acacia Pharma has a therapeutic focus in cancer supportive care
– The management of symptoms of cancer and the side effects of
treatment of cancer
• This therapeutic focus provides
– Focused sales route via specialty hospital physician, the oncologist
– A clear commercial opportunity with a coherent set of conditions
Cancer supportive care – the opportunity
Cancer supportive
care publications
400
300
200
100
0
Healthier patients can tolerate higher doses of cancer therapy
Improve the patients’ quality of life (QoL)
Cancer supportive care – the commercial
opportunity
• Significant commercial successes within cancer supportive care
–
–
–
–
–
–
Erythropoietins for cancer related anaemia (eg Aranesp, $4.4bn*)
GCSFs for neutropenia (eg Neupogen, $1.4bn)
5HT3-antagonists for nausea & vomiting (eg Zofran, $1bn)
Bisphosphonates for metastatic bone disease (eg Zometa, $1.2bn)
CR opioids for cancer pain (eg Oxycontin, $3bn)
IR opioids for cancer breakthrough pain (eg Actiq, $284m)
• Despite this there appear to be
– Limited product opportunities in development (PharmaProjects &
Datamonitor 2007)
– Few companies focused within the space
• Significant opportunity existed for Acacia to become a leading
cancer supportive care company
* 30-40% sales in CSC
Discovery & development
Condition
Unmet
need
Required
biology
Drug/
delivery
Patents
• Discovery & development based on established drugs
– Higher probability of success, more rapid development, lower cost
• Commercially led process, driven by unmet needs of the oncologist
• Product differentiation (from marketed drug) and patent protection key
– Significant internal experience
• Process has been used to nominate the four clinical development
opportunities:
– APD209 – cancer cachexia
– APD421 & APD403 – nausea & vomiting (PONV & CINV)
– APD515 – xerostomia in advanced cancer patients
Cancer cachexia – market need
Condition
Unmet
need
Required
biology
• Cancer cachexia is an area of enormous unmet need
– Complex condition, multiple metabolic dysfunctions and cytokine
abnormalities, present in 50% of cancer patients; strong association
with poorer survival and reduced QoL
• Major unmet needs exists - no approved therapy or gold standard
– Physicians seek
• Increased body weight, specifically muscle mass and function
• Increased appetite, normal function and fuel for increased mass
• Multiple mechanisms are required to get broad efficacy in this
highly complex condition
– Modulation of key cytokines
– Anabolism, and preferably anti-catabolism
Cancer cachexia – APD209
Required
biology
Drug/
delivery
Patents
• Pharmacological target profile (PTP) – multifactorial pharmacology
– Down-regulation of cytokines TNFα, IL-1, IL-6 and IFNγ
• Rectify abnormalities and stimulate appetite
– Down-regulation of ubiquitin and caspase pathways
• Produce anabolism and anti-catabolism
• Acacia identified a product having the required pharmacological profile
• APD209 is an oral combo product, based on a known drug delivered
currently by a “non-oral” route, for the new use cancer cachexia
– New use and delivery provides both differentiation and IP
– Sales estimated ~£300 million per annum
• Significant upside available in other muscle wasting conditions (eg frailty)
• Currently being investigated in a Phase IIa clinical study
APD209 – preclinical data
• APD209 tested in Yoshida AH130 hepatoma model
– Seven day model which rapidly produces cachexia
– APD209 increased
• Appetite (food intake)
• Overall weight (body & carcass)
• Muscle mass (gastrocnemius – calf muscle)
Effect of APD209 in cachexia model
% increase vs control
35
30
***
25
Food intake
20
***
15
*
10
Body weight
Carcass weight
*
Gastrocnemius
5
0
Food intake
Body weight
Carcass weight
Gastrocnemius
p<0.05*
p<0.001***
Nausea & vomiting – market need
Condition
Unmet
need
Required
biology
• Nausea & vomiting (NV) is a complex multi-pathway condition
– Dopamine, neurokinin, serotonin, opioid, histamine involved
• Despite the products available on the market, a clear unmet needs
still exists (MR and KOLs)
– Improved efficacy, in particular
•
•
•
•
Ability to reduce nausea
Late stage CINV
Effective against opiate induced sickness
Safe D2 antagonist for PONV
• Particular need for safe D2 antagonism following the demise of
droperidol, a particularly good anti-nauseant
Nausea & vomiting – APD421 & APD403
Required
biology
Drug/
delivery
Patents
• Pharmacological target profile (PTP) generated
• Identified a widely marketed, safe, oral drug, that meets the above
– APD421/APD403 appears to be a “safe droperidol”
• APD421/APD403 is an IV formulation of this known drug for the new
use of nausea & vomiting
– IV route is route of choice for the anaesthetist and oncologist
• Ability to formulate drug in non-invasive presentations for use at home
– New use and delivery route provides both differentiation and IP
– APD421 sales estimated >£200 million pa in post-operative N&V (PONV)
– Similar sales estimated for APD403 in chemotherapy-induced N&V (CINV)
• Clinical proof-of-concept to be initiated 1Q2011
APD421 – preclinical data (PONV)
• APD421 tested in gold standard ferret model
– Morphine (a risk factor for PONV) used as emetogen
– Significant anti-emetic effects seen in this challenging model
APD421 vs morphine challenge
50
40
30
20
10
0
VEHICLE
3mg/kg
Retches
6mg/kg
Vomits
Emesis periods
12mg/kg
APD403 – preclinical data (CINV)
• APD403 tested in gold standard ferret model
– Cisplatin (highly emetogenic chemotherapy) used as emetogen
– Significant anti-emetic effects seen at very low doses
APD403 vs cisplatin challenge
100
90
80
70
60
50
40
30
20
10
0
VEHICLE
0.2mg/kg
0.6mg/kg
Retches
Vomits
2mg/kg
Emesis periods
6mg/kg
Droperidol 3mg/kg
Xerostomia – market need
Condition
Unmet
need
Required
biology
• Xerostomia is dry mouth due to change in composition or amount of
secreted saliva
– Discomfort, difficulty eating, dental caries and infection
• Up to 80% of advanced cancer patients suffer from the condition
primarily associated with chemo & concomitants (MR and KOLs)
– No registered treatment
– Systemic salivary stimulants used off label
• High side effect and high tablet burden
– Patient and physician seeks local treatment
• Local salivary stimulation required
– Targeting the local salivary glands which are responsible for production of
mucins and mouthfeel
Xerostomia – APD515
Required
biology
Drug/
delivery
Patents
• Pharmacological target profile (PTP) generated
– Salivary stimulant with appropriate physical chemistry for local delivery
• Identified a marketed, oral drug, that meets the above criteria
• APD515 is an optimised buccal formulation of this known drug for
the new use of xerostomia in advanced cancer
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–
–
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Buccal delivery meets physician and patient requirements
New use and delivery provides both differentiation and IP
Sales estimated >£120 million per annum in initial indication
Significant upside in hospital - early cancer, head & neck, Sjögren's, but
also in the general geriatric primary care market
• Phase I to be initiated 4Q2010 with Phase II starting 2Q2011
APD515 – preclinical data
• APD515 tested in rabbit model (similar physiology to humans)
– Up to five fold increase in salivary flow for duration of experiment (2hrs)
Milestones to the end of 2011
Product opportunity Value adding milestone
Date
APD209
- cachexia
Complete Phase II Pilot
Initiate licensing plan
Mar 2011
May 2011
APD421 & APD403
- nausea & vomiting
Initiate Phase II PoC in cancer pts
Complete Phase II PoC
Jan 2011
Mar 2011
APD515
- xerostomia
Initiate and complete Phase I PK
Initiate Phase II dose ranging
Complete Phase II dose ranging
Dec 2010
Jun 2011
Oct 2011
APD421
- PONV
Initiate Phase II dose ranging*
Complete Phase II dose ranging
Jun 2011
Dec 2011
* Subject to further funding
Exit opportunities
• Acacia Pharma provides investors with a number of exit opportunities
– Trade sale based on cancer supportive portfolio at end of Phase II (2012)
• Valuations could be up to £150m at the end of Phase II (based on the sum of
heavily discounted NPVs)
– Divestment of specific products at the end of Phase II (PanGenetics model)
• Value linked to project’s NPV, we know there is an appetite for our projects
– Other exit options exist
• Exit post Phase III - substantially improved valuation, but more time and more
investment required
• IPO, not currently available, but our model supports this (late stage pipeline with
opportunity to sell in-house)
• Key is to provide Board with options
– Management experienced in deal doing
– Significant number of companies are interested in the space
– Portfolio lends itself to having different options available
Summary
• Focused cancer supportive care company with a leadership
position in the area
• Lower risk development business model, that delivers product
opportunities of high value in a cash efficient manner
• Experienced management team supported by appropriate
external experts
• Supportive investor base
• Pipeline comprising four clinical stage developments
– Rapid milestone achievement
• Commercially attractive products providing the opportunity to
deliver significant return to stakeholders