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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 – – – – 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