Focus on Pulmonology and Hepatology. In Pulmonology focused on Idiopathic Pulmonary Fibrosis (IPF) and in Hepatology Protease Inhibitor recent collaboration with Roche and an undisclosed preclinical compound (in collaboration with Array).
IPF • Scarring of lungs, unknown cause • Median survival from diagnosis 2-5 years • US Prevalence (for PF) 128,000, Incidence 48,000 each year http://tinyurl.com/u6kgo, journal abstract http://tinyurl.com/tqd6m IPF prevalence incidence 83K US and 30K incidence. • No approved therapy steroid and immune suppressants used with little effect. Drugs used include: Imuran (Azathioprine), Cellcept (Mycophenolate mofetil), Rheumatrex (Methotrexate), Mucomyst/Parvolex (N-acetylcysteine [NAC]) and Prednisone along with off-label use of Actimmune. Other off-label use include: Remicade (Infliximab), Enbrel (Etanercept) and Gleevec (Imatinib).
Competitive Landscape for IPF 1. Genzyme (collaboration with what was CAT) in Phase 1 2. Bosentan (Tracleer) from Actelion, Phase 2 failed in their endpoint proceeding with Phase III (BUILD-3) believed to be mortality end point 390 patients, event-driven study with SPA, results expected late 2009. 3. Imatinib (Gleevec), I believe it failed Phase 2 not sure of status going forward. 4. Sildenafil (Phase 2) http://www.clinicaltrials.gov/ct/show/NCT00352482 5. Pipex (Tetrathiomolybdate) Phase I-II completed http://clinicaltrials.gov/ct/show/NCT00189176 Company filings say plans to initiate Phase 3 6. FivePrime Collaboration http://tinyurl.com/yz444l 7. Others?
Actimmune • INSPIRE Trial DSMB stopped at interim analysis for lack of efficacy, http://tinyurl.com/37y9tn • For more information on Actimmune please see prior ReadMe files
Pirfenidone • Administration Orally active small molecule 3x day pill of either 267 mg capsules (CAPACITY 1) or 267 mg or 133 mg (CAPACITY 2) • Acquired NA and EU rights from Marnac, http://www.marnac.com/ for Fibrotic Indications. (PR http://tinyurl.com/yy2qao and 10K’s) In March 2002, we licensed from Marnac, Inc., a privately held biopharmaceutical company, and its co-licensor, KDL GmbH, their worldwide rights, excluding Japan, Korea and Taiwan, to develop and commercialize pirfenidone for all fibrotic diseases, including pulmonary, liver and renal fibrosis. Under the terms of the agreement, we received an exclusive license from Marnac and KDL in exchange for an up-front cash payment of $18.8 million and future milestone and royalty payments. • Method Of Action (Company presentations) Preferentially binds to and disables the kinase p38-gamma. Significantly inhibits TGF-beta synthesis (fibrosis), Also inhibits TNF-alpha synthesis (inflammation) • IP Protection (Conference call) Older compound patent from Marnac licensed covering anti-fibrotic uses 2011 expires. Basis of exclusivity more on Orphan drug. Granted in US (7 years) and Europe (10 years) after approval. Company states on Q4 2006 call that it is working on expanding IP and have certain activities and progress (very vague could be anything from follow-on compound to exploring new patents). Also stated at SIGnificant Investment conference 3/07 • Other Indications being studied in a number of trials (not all by InterMune). InterMune is seeking approval in Idiopathic Pulmonary Fibrosis. It is also conceivable that they later seek a broader approval for Fibrotic disease of the lung. Most notably an NIH study in Hermansky Pudlak Syndrome. • Shionogi Phase 2 Results PRhttp://tinyurl.com/y5nwel Stopped after 6 months (efficacy). Treatment of 9 month. Observation/ Placebo/ Pirfenidone: Improved Minimal O2 Oximetry/6.1%/24.2% Declined Saturation/33.3/18.2% P=.016 Vital Capacity Improved/0%/9% Vital Capacity Declined/36.4%/13.4% P=.003 • InterMune Phase 2 Results PRhttp://tinyurl.com/y49zp7 • Journal Articleshttp://ajrccm.atsjournals.org/cgi/content/full/171/9/1040 (Shionogi Phase 2), http://ajrccm.atsjournals.org/cgi/content/full/159/4/1061 • Shionogi Phase 3 Top Line PRhttp://www.shionogi.co.jp/ir_en/news/detail/e_061222.pdf
CAPACITY Trials, http://www.capacitytrials.com/ http://www.clinicaltrials.gov/ct/show/NCT00287729 http://www.clinicaltrials.gov/ct/show/NCT00287716 - Three Arm Study • Primary endpoint is change in forced vital capacity (FVC) after 60 weeks of treatment • Two concurrent, multi-national trials CAPACITY 1 and CAPACITY 2 • Approximately 585 patients • Randomized first patient April 27, 2006 • Expect enrollment to conclude Q4 of 2007, with top-line data expected in early 2009 • Exploring European partnering opportunities • Enrollment proceeding “Very Well” (according to Q4 call) company still maintains enrollment expected to complete in Q4 2007. • Differences between CAPACITY and Shionogi Phase 3 (Company presentations) Shionogi 250 patients, ours I-260, II-325, roughly same. Length Shionogi-52 ours 60 weeks. Dosing in Shionogi low dose 400mg TID high 600 TID, CAPACITY I-800mg TID, CAPACITY II 800mg and 400mg both TID, if account for avg. body weight of US/EU vs. Japan about 30mg/kg in each. Endpoint Shionogi change in Vital Capacity ours Change in Percent Predicted Forced Vital Capacity. Comparable measures of lung volume. Other difference is the patient population, Shionogi is Japanese ours is mainly NA and EU do not know of any metabolism difference in population or Pirfenidone between two groups.
InterMune 191 / PI Program • Collaboration began with Array BioPharma http://tinyurl.com/y75d42 • Royalties due Described as “mid-single digits”. Array describes their royalties as 3% (generally speaking about royalty deals they have in past not just 191). As pointed out by rkrw (SI) and Dew other 3rd party royalties Chiron/others (~2%?) • 191 General Characteristics 1. Active Sight NS3/4 PI 2. High affinity for and stability in the liver 3. Favorable pharmacokinetic profile potential Q12/BID dosing. 4. Good safety margins for: Body weights, organ weights, Clinical chemistry, clotting parameters and hematology, Renal, neurologic, gastrointestinal, immune and cardiovascular systems 5. Potency of ITMN compound is maintained against mutations that show resistance to other protease inhibitors 6. HCV protease selectivity is high 7. There were no significant effects on microscopic histopathology on any organ or tissue, including heart and liver • 191 more specifics 1. Replicon Potency (genotype 1) EC-50 1.6nM, EC-90 14.1nM, EC-99 155.3, EC-999 1567.3 nM 2. 28 day preclinical tox suggests safe over wide dose range 3. Mutants D168A primary driver of 191 sensitivity. Hypersensitive mutation to Pegasys shift by about order may suggest suggests combo will result in protection against mutation. 4. Rat studies (looking at livers) various dose concentrations including 16 hours above EC 99.9 (3 log drop) 30 mg/kg equiv about 300mg in human to get similar human concentration. • Some comparisons to VX-950/other PI’s 1. HCV replicon EC50 = ~2nM (VX-950=402nM, SCH-503034=200nM) 2. Mutations resistant to other PI primarily A156T 191 is highly active against mutation indicating complimentary profile with other PI’s in development • 9/26/06 CTA submitted to the French Medicinal and Biological Products Evaluation Directorate http://tinyurl.com/yevhgh • For technically oriented suggest listening to Think Equity “Think Tank” presentation by Dr. Blatt on 11/10/06 most technical info in company presentation to date. • Phase 1A Trial Informationhttp://tinyurl.com/32lvtz 1. One clinical trial site in Europe and will enroll approximately 74 healthy volunteers. 2. First patient dosed early January 2007. 3. Single-dose ascending dose in healthy volunteers. 4. Expects to complete the currently running Phase 1a study of ITMN-191 in healthy subjects in the first half of 2007. 5. Schering and Vertex held 1A until 1B that could be something we’ll do and have not disclosed plans yet. • Phase 1B Trial Information (Press release/call) “InterMune plans to evaluate ITMN-191 in a Phase 1b randomized, double- blind, placebo controlled, multiple ascending dose study in patients infected with chronic hepatitis C virus. ITMN-191 will be administered to treatment naïve patients for 14 days and the study will include a cohort of non- responder patients. InterMune and its partner Roche expect to announce initial viral kinetic results from the Phase 1b trial in the second half of 2007.” 1. Not disclosing number of patients at this point 2. A specific cohort of non-responders in our mono-therapy studies so we can understand is there any difference in kinetics between non-responders and naïve patients. Ours will be the first in systematic fashion look at those directly. 3. We have very clear definition of what it means to be non-responder as operational defined in protocol. Will be a homogeneous group. (in response to question about type of non-responders) • Other 191 Information 1. Looking at addition of ribavirin toxicology and PK (preclinical). 2. Plan to move quickly into Phase 2 of a design and duration of what would want to do in Phase 3 which you may imagine would include PEG-Interferon and Ribavirin.
Roche Collaboration http://tinyurl.com/y2e87x • 60 million on closing, assuming successful develop in US and other countries will receive up to 470 million in milestones. 530 million total. Potentially 35 million (of 470 million) in next 12 months. • Cost sharing – Roche responsible for 67% global development costs including all related mfg costs. • Royalties outside US Roche commercializes all products from collaboration InterMune Royalties “mid-high teens %” depending on net sales level • In US commercialize and share profits on 50/50 basis. • Same economic terms would cover any 2nd generation PI’s developed and commercialized, roughly doubling value. Note this was clarified to mean excluding the up-front payment. • Roche responsible for World-wide formulation development and manufacturing any compound. • InterMune has 3rd party royalty obligations that total in mid single digits. Split 50/50 with Roche in US, InterMune responsible for them outside US • Development self funding through development. Beyond significant post development milestones. • Can opt out of either co-development or com-commercialization. If do so would receive higher x-US royalties and same royalties replace profit share in US. • Expect to close pending Hart-Scott-Rodino around mid November
Other Pipeline/Interests • Early stage preclinical program partnered with Array (undisclosed indication in Hepatology). Royalty described by Array as high single digits. Array Responsible for creating clinical trial and all synthetic process. InterMune take into clinical development through commercialization. • Equity interest in Targanta Therapeutics, http://www.targanta.com/ as a result of selling Oritavancin in December 2005. (http://tinyurl.com/yznhod) • Early stage work on PEGylated version of Actimmune (with Maxygen), does not appear to have much effort as this time. (http://tinyurl.com/yn4e4z) • PEG-Alfacon (PEGylated version of Infergen) appears unlikely to be further developed. • Research work in both Hepatology and Pulmonology
Financials • Cash/securities 211.1 million (end of Q1 2007) • 170 million convertible. Coupon rate .25%. 2011 maturity. Conversion Price $21.63. • Shelf registration (http://tinyurl.com/29rsqc) for up to 175 million filed 12/28/2006 • 34 million shares outstanding • 2007 Guidance o Revenue (was 70– 90 million, removed with March INSPIRE study being stopped for futility) o COGS (was 21-23%, removed with March INSPIRE study being stopped for futility) o R&D 100-110 million. Including 5-10 million for est. FAS 123R. o SG&A 30-35 million including 5-10 million for FAS 123R, , excludes INSPIRE discontinuation expenses and possible contract wind-down costs (for Actimmune). • Government settlement for past Actimmune promotion (http://tinyurl.com/y3wa8a) . The company will pay $36.9 million plus 5% interest over five years. The first annual installment of $5 million paid in 2006. Note some acceleration terms exist should InterMune receive 150 million in partnering/licensing (capped at $10 million/year).
Time-Line/Medical Presentations • Present 8 abstracts from Pulmonology research at ATS in May • Present 3 abstracts of preclinical experience of 191 at EASL in April • DDW poster on HCV binding kinetics of 191 • Q4 ’07 191 Phase 1B data • Q4 ’08 Top line results from CAPACITY
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