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This strategic combination will create one of the leading oncologyfranchises in the biopharmaceutical industry, offering both targeted therapiesand oncolytic agents along with a pipeline spanning all phases of clinicaldevelopment. The combined oncology portfolio will target a broader array ofsolid tumor types including lung, breast, ovarian, colorectal, head and neck,and pancreatic, positioning Lilly to pursue treatments of multiple cancers.Combining with ImClone will further strengthen Lilly's growing portfolio offirst-in-class and best-in-class pharmaceutical products, enabling Lilly tobetter support oncologists, with the ultimate goal of delivering betteroutcomes for cancer patients. Importantly, the combination also expandsLilly's biotechnology capabilities. ImClone's state-of-the-art development andcommercial manufacturing facility will provide significant flexibility todevelop and manufacture complex biomolecules.
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"We think very highly of ImClone's ground-breaking work in oncology,particularly its success with ERBITUX(R), a blockbuster targeted cancertherapy, and its ability to advance promising biotech molecules in itspipeline," said John C. Lechleiter, Ph.D., Lilly's president and chiefexecutive officer. "We are excited about the possibilities of improvingoutcomes for individual patients and building value for shareholders. Thistransaction will broaden our portfolio of marketed cancer therapies and boostLilly's oncology pipeline with up to three promising targeted therapies inPhase III in 2009. By bringing together ImClone's and Lilly's marketedoncology products, pipelines, and biotech capabilities, we are taking a veryimportant step forward in addressing the challenges of patent expirations wewill face early in the next decade. We look forward to working with theImClone team and their partners to ensure a smooth transition."
John H. Johnson, ImClone's chief executive officer, said "We believe thisis an important step forward in ImClone's and Lilly's shared goal ofaddressing the medical needs of cancer patients around the world. Thesignificant progress ImClone has made over the last few years is a directresult of the important contributions of our employees, and joining forces atthis stage of our growth will allow us to leverage Lilly's global capabilitiesand make even greater advancements in our proprietary pipeline."
ERBITUX is marketed by ImClone's two partners, Merck KGaA and Bristol-Myers Squibb (BMS), and ImClone co-promotes ERBITUX in North America togetherwith BMS. ERBITUX is indicated as both a single agent and with chemotherapyfor certain types of colorectal cancers and as a single agent or incombination with radiation therapy for head and neck cancers. In 2007,worldwide sales of ERBITUX grew 18 percent to approximately $1.3 billion.
Benefits of the Transaction
A key strategic priority for Lilly is increasing the flow of high-quality,innovative new therapies. Today, Lilly has approximately 50 molecules inclinical development and the strongest mid-stage pipeline in its history. Thecompany continues to evaluate and execute on opportunities to help bolster itspipeline, including the in-licensing of promising molecules and targetedacquisitions. The acquisition of ImClone adds late-stage assets, early- andmid-stage prospects, and the opportunity to generate additional value fromERBITUX. Importantly, it also supports the company's strategy to furtherincrease its focus on biotechnology by increasing the proportion of itspipeline represented by biologics.
-- Broadens Lilly's current oncology product portfolio. The transactionwill immediately enable Lilly to offer physicians and their patients acomplementary portfolio of leading oncolytic agents and targeted therapiesincluding GEMZAR(R), ALIMTA(R) and ERBITUX.
-- Strengthens Lilly's oncology pipeline and biotech capabilities. Lillyhas a rich history and deep expertise in oncology which will be augmented byImClone's culture of discovery. ImClone's pipeline adds several molecules inmid-to late-stage clinical development targeting virtually all major solidtumor types. These targeted therapies, three of which have the potential to bein Phase III in 2009, add to Lilly's own oncology pipeline of 13 compounds inclinical development. Lilly's biotech capabilities will be complemented andenhanced by ImClone's expertise in the scale-up and manufacturing ofbiologics. In addition, ImClone's state-of-the-art development and commercialmanufacturing facility will offer additional capacity for antibodies indevelopment from both companies.
-- Provides important source of growth beginning in period of patentexpirations. The acquisition of ImClone will help Lilly meet the challengeposed by patent expirations on several currently marketed products in themiddle of the next decade. ERBITUX has significant future growthopportunities, including from potential new indications in first-line head andneck, colorectal and non-small cell lung cancer. Given that three ofImClone's pipeline assets have the potential to be in Phase III testing in2009, they could also contribute significantly to Lilly's revenue growthduring this period, while ImClone's earlier stage assets should help bolsterLilly's late-stage pipeline.
Promising ImClone Pipeline Molecules
-- IMC-1121B is a fully-human monoclonal antibody that targets the VEGFreceptor to deprive tumor blood vessels of the nutrients they need for furthergrowth. Phase II studies are underway for metastatic melanoma, renal, liver,ovarian and prostate cancers. Metastatic breast cancer is in Phase IIItesting, while Phase III testing in gastric cancer may begin in 2009.
-- IMC-A12 is a fully-human monoclonal antibody that targets the insulin-like growth factor-1 receptor (IGF-1R). Phase II testing is underway inbreast, prostate, pancreatic, colon, liver and head and neck cancers, as wellas sarcoma, with Phase III trials planned in 2009. IMC-A12 has the potentialto work with a variety of other targeted agents.
-- IMC-11F8 is a potent, fully human monoclonal antibody that targets theepidermal growth factor receptor (EGFR), the same receptor targeted byERBITUX. It is currently in Phase II studies for metastatic colorectal cancerwith one or more Phase III trials planned in 2009.
Terms
Under the terms of the agreement, Lilly (through a wholly-ownedsubsidiary) will acquire ImClone through an all cash tender offer of $70.00per share, followed by a merger of Lilly's subsidiary with ImClone. Lilly isexpected to commence the tender offer as soon as practicable. The transactionis conditioned upon at least a majority of the outstanding ImClone sharesbeing tendered, as well as clearance under the Hart-Scott-Rodino AntitrustImprovements Act, similar requirements outside the U.S., and other customaryclosing conditions. The transaction is not subject to any financing conditionand is expected to close in either the fourth quarter of 2008 or the firstquarter of 2009.
Upon the closing of the transaction, Lilly will incur a one-time charge toearnings for acquired in-process research and development, but it is prematureto estimate what that charge will be. The company expects the transaction tobe accretive to earnings on a cash basis in 2012 and on a GAAP basis in 2013.
Advisors
UBS Investment Bank is acting as lead financial advisor to Lilly andDeutsche Bank is also serving as financial advisor. Latham & Watkins LLP isacting as legal counsel to Lilly. J.P. Morgan is acting as financial advisorto ImClone and Katten Muchin Rosenman LLP is acting as ImClone's legalcounsel.
Conference Call and Webcast
Lilly will conduct a conference call with the investment community andmedia today at 9:00 a.m. EDT to discuss today's announcement. Investors,media and the general public can access a live webcast of the conference callthrough the Webcasts & Presentations link that will be posted on Lilly'swebsite at www.lilly.com. The webcast of the conference call will beavailable for replay through November 6, 2008.
Important Information about the Tender Offer
The press release is for informational purposes only and is neither anoffer to purchase nor solicitation of an offer to sell securities. The tenderoffer for the outstanding shares of ImClone common stock described in thispress release has not commenced. At the time the offer is commenced, AlaskaAcquisition Corporation and Eli Lilly and Company will file a tender offerstatement on Schedule TO with the Securities and Exchange Commission, andImClone will file a solicitation/recommendation statement on Schedule 14D-9,with respect to the tender offer. The tender offer statement (including anoffer to purchase, a related letter of transmittal and other offer documents)and the solicitation/recommendation statement will contain importantinformation that should be read carefully before any decision is made withrespect to the tender offer. Those materials will be made available to ImCloneshareholders at no expense to them. In addition, all of those materials (andall other offer documents filed with the SEC) will be available at no chargeon the SEC's website: www.sec.gov.
About ERBITUX (Cetuximab)
ERBITUX (cetuximab) is a monoclonal antibody (IgG1 Mab) designed toinhibit the function of a molecular structure expressed on the surface ofnormal and tumor cells called the epidermal growth factor receptor (EGFR,HER1, c-ErbB-1). In vitro assays and in vivo animal studies have shown thatbinding of ERBITUX to the EGFR blocks phosphorylation and activation ofreceptor-associated kinases, resulting in inhibition of cell growth, inductionof apoptosis, and decreased matrix metalloproteinase and vascular endothelialgrowth factor production. In vitro, ERBITUX can mediate antibody-dependentcellular cytotoxicity (ADCC) against certain human tumor types. In vitroassays and in vivo animal studies have shown that ERBITUX inhibits the growthand survival of tumor cells that express the EGFR. No anti-tumor effects ofERBITUX were observed in human tumor xenografts lacking EGFR expression.
Squamous Cell Carcinoma of the Head and Neck (SCCHN)
ERBITUX, in combination with radiation therapy, is indicated for theinitial treatment of locally or regionally advanced squamous cell carcinoma ofthe head and neck.
ERBITUX, as a single agent, is indicated for the treatment of patientswith recurrent or metastatic squamous cell carcinoma of the head and neck forwhom prior platinum-based therapy has failed.
Colorectal Cancer
ERBITUX, as a single agent, is indicated for the treatment of EGFR-expressing metastatic colorectal cancer after failure of both irinotecan- andoxaliplatin-based regimens. ERBITUX, as a single agent, is also indicated forthe treatment of EGFR-expressing metastatic colorectal cancer in patients whoare intolerant to irinotecan-based regimens.
ERBITUX, in combination with irinotecan, is indicated for the treatment ofEGFR-expressing metastatic colorectal carcinoma in patients who are refractoryto irinotecan-based chemotherapy. The effectiveness of ERBITUX in combinationwith irinotecan is based on objective response rates. Currently, no data areavailable that demonstrate an improvement in disease-related symptoms orincreased survival with ERBITUX in combination with irinotecan for thetreatment of EGFR-expressing metastatic colorectal carcinoma.
For full prescribing information, including boxed WARNINGS regardinginfusion reactions and cardiopulmonary arrest, visit http://www.ERBITUX.com.
IMPORTANT SAFETY INFORMATION
Infusion Reactions
-- Grade 3/4 infusion reactions occurred in approximately 3% of patientsreceiving ERBITUX (Cetuximab) in clinical trials, with fatal outcome reportedin less than 1 in 1000
- Serious infusion reactions, requiring medical intervention andimmediate, permanent discontinuation of ERBITUX, included rapid onset ofairway obstruction (bronchospasm, stridor, hoarseness), hypotension, loss ofconsciousness, and/or cardiac arrest
-- Most (90%) of the severe infusion reactions were associated with thefirst infusion of ERBITUX despite premedication with antihistamines
- Caution must be exercised with every ERBITUX infusion, as there werepatients who experienced their first severe infusion reaction during laterinfusions
- Monitor patients for 1 hour following ERBITUX infusions in a settingwith resuscitation equipment and other agents necessary to treat anaphylaxis(eg, epinephrine, corticosteroids, intravenous antihistamines,bronchodilators, and oxygen). Longer observation periods may be required inpatients who require treatment for infusion reactions
Cardiopulmonary Arrest
-- Cardiopulmonary arrest and/or sudden death occurred in 4 (2%) of 208patients with squamous cell carcinoma of the head and neck treated withradiation therapy and ERBITUX, as compared to none of 212 patients treatedwith radiation therapy alone. Fatal events occurred within 1 to 43 days afterthe last ERBITUX treatment
- Carefully consider the use of ERBITUX in combination with radiationtherapy in head and neck cancer patients with a history of coronary arterydisease, congestive heart failure or arrhythmias in light of these risks
- Closely monitor serum electrolytes including serum magnesium,potassium, and calcium during and after ERBITUX therapy
Pulmonary Toxicity
-- Interstitial lung disease (ILD), which was fatal in one case, occurredin 4 of 1570 (<0.5%) patients receiving ERBITUX in clinical trials. InterruptERBITUX for acute onset or worsening of pulmonary symptoms. Permanentlydiscontinue ERBITUX where ILD is confirmed
Dermatologic Toxicities
-- In clinical studies of ERBITUX, dermatologic toxicities, includingacneform rash, skin drying and fissuring, paronychial inflammation, infectioussequelae (eg, S. aureus sepsis, abscess formation, cellulitis, blepharitis,cheilitis), and hypertrichosis, occurred in patients receiving ERBITUXtherapy. Acneform rash occurred in 76-88% of 1373 patients receiving ERBITUXin clinical trials. Severe acneform rash occurred in 1-17% of patients
- Acneform rash usually developed within the first two weeks of therapyand resolved in a majority of the patients after cessation of treatment,although in nearly half, the event continued beyond 28 days
- Monitor patients receiving ERBITUX for dermatologic toxicities andinfectious sequelae
ERBITUX plus Radiation Therapy and Cisplatin
-- The safety of ERBITUX in combination with radiation therapy andcisplatin has not been established
- Death and serious cardiotoxicity were observed in a single-arm trialwith ERBITUX, radiation therapy, and cisplatin (100 mg/m2) in patients withlocally advanced squamous cell carcinoma of the head and neck
- Two of 21 patients died, one as a result of pneumonia and one of anunknown cause
- Four patients discontinued treatment due to adverse events. Two ofthese discontinuations were due to cardiac events
Electrolyte Depletion
-- Hypomagnesemia occurred in 55% (199/365) of patients receiving ERBITUXand was severe (NCI CTC grades 3 & 4) in 6-17%. The onset of hypomagnesemiaand accompanying electrolyte abnormalities occurred days to months afterinitiation of ERBITUX therapy
- Monitor patients periodically for hypomagnesemia, hypocalcemia andhypokalemia, during, and for at least 8 weeks following the completion of,ERBITUX therapy
Late Radiation Toxicities
-- The overall incidence of late radiation toxicities (any grade) washigher with ERBITUX in combination with radiation therapy compared withradiation therapy alone. The following sites were affected: salivary glands(65%/56%), larynx (52%/36%), subcutaneous tissue (49%/45%), mucous membranes(48%/39%), esophagus (44%/35%), and skin (42%/33%) in the ERBITUX andradiation versus radiation alone arms, respectively
- The incidence of grade 3 or 4 late radiation toxicities were similarbetween the radiation therapy alone and the ERBITUX plus radiation therapyarms
Pregnancy
-- In women of childbearing potential, appropriate contraceptive measuresmust be used during treatment with ERBITUX and for 6 months following the lastdose of ERBITUX. ERBITUX should only be used during pregnancy if the potentialbenefit justifies the potential risk to the fetus
Adverse Events
-- The most serious adverse reactions associated with ERBITUX across allstudies were infusion reactions, cardiopulmonary arrest, dermatologic toxicityand radiation dermatitis, sepsis, renal failure, interstitial lung disease,and pulmonary embolus
-- The most common adverse reactions associated with ERBITUX (incidencegreater than or equal to 25%) are cutaneous adverse reactions (including rash,pruritus, and nail changes), headache, diarrhea, and infection
-- The most frequent adverse events seen in patients with carcinomas ofthe head and neck receiving ERBITUX in combination with radiation therapy(n=208) versus radiation alone (n=212) (incidence greater than or equal to50%) were acneform rash (87%/10%), radiation dermatitis (86%/90%), weight loss(84%/72%), and asthenia (56%/49%). The most common grade 3/4 adverse events(greater than or equal to 10%) included: radiation dermatitis (23%), acneformrash (17%), and weight loss (11%)
-- The most frequent adverse events seen in patients with metastaticcolorectal cancer (n=288) in the ERBITUX + best supportive care arm (incidencegreater than or equal to 50%) were fatigue (89%), rash/desquamation (89%),abdominal pain (59%), and pain-other (51%). The most common grade 3/4 adverseevents (greater than or equal to 10%) included: fatigue (33%), pain-other(16%), dyspnea (16%), abdominal pain (14%), infection without neutropenia(13%), rash/desquamation (12%), and other-gastrointestinal (10%)
-- The most frequent adverse events seen in patients with metastaticcolorectal cancer (n=354) treated with ERBITUX plus irinotecan in clinicaltrials (incidence greater than or equal to 50%) were acneform rash (88%),asthenia/malaise (73%), diarrhea (72%), and nausea (55%). The most commongrade 3/4 adverse events (greater than or equal to 10%) included: diarrhea(22%), leukopenia (17%), asthenia/malaise (16%), and acneform rash (14%)
Important Safety Information for ALIMTA
ALIMTA is approved by the FDA in combination with cisplatin (anotherchemotherapy drug) for the initial treatment of advanced nonsquamous non-smallcell lung cancer (NSCLC), a specific type of NSCLC. ALIMTA is not indicatedfor patients who have a different type of NSCLC called squamous cell.
ALIMTA is approved by the FDA as a single agent (used alone) for thetreatment of patients with advanced nonsquamous non-small cell lung cancer(NSCLC), a specific type of NSCLC, after prior chemotherapy. ALIMTA is notindicated for patients who have a different type of NSCLC called squamouscell.
ALIMTA is a treatment for Malignant Pleural Mesothelioma (MPM), which is acancer that affects the inside lining of the chest cavity. ALIMTA is givenwith cisplatin, another anti-cancer medicine (chemotherapy) when surgery isnot an option.
Myelosuppression is usually the dose-limiting toxicity with ALIMTAtherapy.
ALIMTA may not be appropriate for some patients. If you are allergic toALIMTA, tell your doctor because you should not receive it. If you think youare pregnant, are planning to be pregnant, or are nursing, please tell yourhealthcare team. ALIMTA may harm your unborn or nursing baby. Your physicianmay advise you to use effective contraception (birth control) to preventpregnancy while you are being treated with ALIMTA.
If you have liver or kidney problems, be sure to tell your doctor. Yourdose of ALIMTA may have to be changed, or ALIMTA may not be right for you.There is a risk of side effects associated with ALIMTA therapy. ALIMTA cansuppress bone marrow function. It is very important to take folic acid andvitamin B12 prior to and during your treatment with ALIMTA to lower yourchances of harmful side effects.
Your healthcare professional will prescribe a medicine called acorticosteroid, which lowers your chances of getting skin reactions withALIMTA. Ask your healthcare professional before taking medicines called NSAIDs(nonsteroidal anti-inflammatory drugs used to treat pain or swelling). Tellyour doctor if you are taking other medicines, including prescription and non-prescription medicines, vitamins, and herbal supplements.
The most common side effects of ALIMTA when given alone or in combinationwith cisplatin, another chemotherapy drug, are low blood cell counts (redblood cells, white blood cells, and platelets); tiredness; stomach upset,including nausea, vomiting, and diarrhea; mouth, throat, or lip sores; loss ofappetite; rash; and constipation.
Call your healthcare professional right away if you have a fever, chills,diarrhea, or mouth sores. These symptoms could mean you have an infection.These are not all of the side effects of ALIMTA. If you have any side effectthat bothers you or that doesn't go away, be sure to talk with your healthcareprofessional.
You will have regular blood tests before and during your treatment withALIMTA. Your doctor may adjust your dose of ALIMTA or delay your treatmentbased on the results of your blood test and on your general condition.
For more information about all of the side effects of ALIMTA, please talkwith your healthcare team, see the complete Prescribing Information atwww.ALIMTA.com, or call 1-800-545-5979.
Important Safety Information for GEMZAR
GEMZAR is indicated in combination with cisplatin (another type ofchemotherapy) for the first-line treatment of patients with locally advanced(stage IIIA or stage IIIB) or metastatic (stage IV or cancer that has spread)non-small cell lung cancer for whom surgery is not possible.
Myelosuppression is usually the dose-limiting toxicity with GEMZARtherapy.
GEMZAR may not be appropriate for some patients. If you are allergic toGEMZAR, tell your doctor you should not receive it. GEMZAR can suppress bonemarrow function. There have been rare reports of serious kidney or livertoxicity with GEMZAR treatment, sometimes fatal. Serious lung toxicity hasalso been reported, sometimes fatal. If you think you are pregnant, areplanning to be pregnant, or are nursing, please tell your healthcare team.GEMZAR may harm your unborn or nursing baby.
If you have had prior kidney or liver problems or impairment, please tellyour healthcare professional. GEMZAR may not be right for you. GEMZAR has notbeen shown to work in children. Tell your doctor if you are taking othermedicines, including prescription and non-prescription medicines, vitamins, orherbal supplements.
There is a risk of side effects associated with GEMZAR therapy. The mostcommon side effects are low blood cell counts (red blood cells, white bloodcells, and platelets); fever; infection; hair loss; tiredness; nausea,vomiting, constipation, and diarrhea; rash; shortness of breath; muscle aches;and numbness or tingling in your toes or fingers. These are not all of theside effects of GEMZAR. If you have any side effect that bothers you or thatdoesn't go away, be sure to talk with your healthcare professional. Call yourhealthcare professional right away if you have fever or chills. These symptomscould mean you have an infection.
You will have regular blood tests before and during your treatment withGEMZAR. Your doctor may adjust your dose of GEMZAR or delay your treatmentbased on the results of your blood test and on your general condition.
For more information about all of the side effects of GEMZAR, please talkwith your healthcare team, see the complete Prescribing Information atwww.GEMZAR.com, or call 1-800-545-5979.
You are encouraged to report negative side effects of prescription drugsto the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
About ImClone Systems Incorporated
ImClone Systems Incorporated is a fully integrated biopharmaceuticalcompany committed to advancing oncology care by developing and commercializinga portfolio of targeted biologic treatments designed to address the medicalneeds of patients with a variety of cancers. The company's research anddevelopment programs include growth factor blockers and angiogenesisinhibitors. ImClone Systems' headquarters and research operations are locatedin New York City, with additional administration and manufacturing facilitiesin Branchburg, New Jersey. For more information about ImClone Systems, pleasevisit the company's web site at http://www.imclone.com.
ERBITUX(R) is a registered trademark of ImClone Systems Incorporated.
With regard to ImClone:
Certain matters discussed in this news release may constitute forward-looking statements within the meaning of the Private Securities LitigationReform Act of 1995 and the Federal securities laws. Although the companybelieves that the expectations reflected in such forward-looking statementsare based upon reasonable assumptions it can give no assurance that itsexpectations will be achieved. Forward-looking information is subject tocertain risks, trends and uncertainties that could cause actual results todiffer materially from those currently expected. Many of these factors arebeyond the company's ability to control or predict. Important factors that maycause actual results to differ materially and could impact the company and thestatements contained in this news release can be found in the company'sfilings with the Securities and Exchange Commission, particularly thosefactors identified as "risk factors" in the company's most recent annualreport of Form 10-K and in its quarterly reports on Form 10-Q and currentreports on Form 8-K. For forward-looking statements in this news release, thecompany claims the protection of the safe harbor for forward-lookingstatements contained in the Private Securities Litigation Reform Act of 1995.The company assumes no obligation to update or supplement any forward-lookingstatements whether as a result of new information, future events or otherwise.
About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growingportfolio of first-in-class and best-in-class pharmaceutical products byapplying the latest research from its own worldwide laboratories and fromcollaborations with eminent scientific organizations. Headquartered inIndianapolis, Ind., Lilly provides answers - through medicines and information- for some of the world's most urgent medical needs. Additional informationabout Lilly is available at www.lilly.com. C-LLY
With regard to Lilly:
This press release contains forward-looking statements that are based onmanagement's current expectations, but actual results may differ materiallydue to various factors. The company cannot guarantee that the merger describedwill close or that the company will realize anticipated operationalefficiencies following any such merger with ImClone .The current credit marketmay increase the cost of financing the transaction. There are significantrisks and uncertainties in pharmaceutical research and development and therecan be no guarantees with respect to the company's or ImClone's pipelineproducts that the products will receive the necessary clinical andmanufacturing regulatory approvals or that they will prove to be commerciallysuccessful. The company's results may also be affected by such factors ascompetitive developments affecting current products; rate of sales growth ofrecently launched products; the timing of anticipated regulatory approvals andlaunches of new products; regulatory actions regarding currently marketedproducts; other regulatory developments and government investigations; patentdisputes and other litigation involving current and future products; theimpact of governmental actions regarding pricing, importation, andreimbursement for pharmaceuticals; changes in tax law; asset impairments andrestructuring charges; acquisitions and business development transactions; andthe impact of exchange rates. For additional information about the factorsthat affect the company's business, please see the company's latest Form 10-Kfiled February 2008 and Form 10-Q filed August 2008. The company undertakes noduty to update forward-looking statements.
(Logo: http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO )- Sun exposure may exacerbate these effects
SOURCE Eli Lilly and Company
