From: test@unify.com
`To: Melissa Loff <melissa.loff@meltmedia.com>
`Subject: Proven survival benefit for your HER2+ MBC patients
`Alt 1: Significant clinical benefit for your HER2+ MBC patients
`
`IMMUNOGEN 2336, pg. 1
`Phigenix v. Immunogen
`IPR2014-00676
`
`

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`PRIMARY ENDPCIINT: OVERALL SURVIVAL {OS}
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`Results. of the randomized. open-label. Phase III EMILIA lriel of KADCTLA [3.6 mgikg IV. Dag.r 1] vs the
`combination cl iapatinio [19:30 mga'day oral. once dairy} and capacitabine {1 Dee mgrmE, oral, Mice daily. Days 1-1-1]
`in 91-day cycles until disease progression in I iFFiP+ MEG patients previously treated with traetuzumab and a
`Iaxane. Primary endpoinle were 08, progresoion-tree survival iPFS]. and salely.1 2
`
`50% improvement in median PFS by independent rerriew1
`- 9.6 months median PFS with KADCYLA vs [5.4 months with lepatinib + eepeciteoine;
`PcflODDt
`
`Boxed WARNINGS: HEPATOTOXICITY, CARDIAC TOXICITY, EMBFWOoFETAL TOXICITY
`' Do not substitute MDCYLA tor or with trastuzumah
`
`- Hepetotoiiioity: Serious hepfl'ldtflxicity' nee been reported, Including liverfellure and
`death in petientie treated with KADCVLA. Monitor eerum treneemineeee and bilirubin
`prior to Initiation of KADCYLA treatment and prior to each KADCYLA dcee. Reduce
`dose or dleoontinue KADCVLA as appropriate In oeeee of increased eerLIm
`traneamineaee or total bilirubln
`
`' Cardiac toxicity: KADC‘I'LA administration Ml? Ifild to reductions In I!“ ventricular
`ejection fraction {LVE F}. Evaluate Ielt ventricular function in ell patients prior to end
`during treatment with KADCYLA. Withheld treatment for clinically significant decreaee
`in Ifift ventricular function
`
`. Em bryo-ietel toxicity: Expoeure to KADCYLA can ree Hit in embryootetel death or birth
`detects. Mid“ patients fit these ritkfi lt‘ld flit “Bad for effective tDMMflmiDn
`
`IMMUNOGEN 2336, pg. 2
`Phigenix v. Immunogen
`IPR2014-00676
`
`IMMUNOGEN 2336, pg. 2
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`For more information about these and other
`
`EMILIA trial endpoints, visit KADCYLA.oom.
`
`Important Safety Information
`
`Additional Important Safety Information
`Left Ventricular Dysfunction {LVD}
`- Patients treated with KADCYLA are at increased risk of developing L‘v'D. In EMILIA, LUD
`occurred in 1.3% of patients in the KADCYLA-treated group and in 3.3% in the comparator
`group. Permanently discontinue KADCYLA if L‘v'EF has not improved or has declined further
`Pregnancy Registry
`- Advise patients to contact their healthcare provider immediately if they suspect they may be
`pregnant. Encourage women who may be exposed to KADCYLA during pregnancy to enroll in
`the MotHEFt Pregnancy Flegistry by contacting 1-600-690—5?20
`Pulmonary Toxicity
`' Cases of interstitial lung disease {ILD}, including pneumonitis, some leading to acute
`respiratory distress syndrome or fatal outcome, have been reported in clinical trials with
`KADGYLA. In EMILIA. the overall frequency of pneumonitis was 1.2%
`- Treatment with KADCYLA should be permanently discontinued in patients diagnosed with ILD
`or pneumonitis
`
`Infirelon-Related Reactions, Hypersensitivity Reactions
`' Treatment with KADCYLA has not been studied in patients WI‘IO had trastuzumalo permanently
`discontinued due to infusion-related reactions (lFtFt) andtor hypersensitivity reactions;
`treatment with KADCYLA is not recommended for these patients. In EMILIA. the overall
`frequency of lHFts in patients treated with KADGYLA was 1.4%
`- KADCYLA treatment should be interrupted in patients with severe lFiFts and permanently
`discontinued in the event of a life-threatening lFlFl. Patients should be closely monitored for
`IFlFis, especially during the first infusion
`Hemorrhage
`' Hemorrhagic events, sometimes fatal, have been reported in clinical trials. In EMILIA, the
`incidence of a Grade 3 hemorrhage was 1 3% in the KADCYLA-treated group and 0.3% in the
`comparator group {overall incidence 32.2% and 16.4%. respectively}
`- In some of the observed cases the patients were also receiving anticoaguiation therapy or
`antiplatelet therapy, or had thrombocytopenia; in others. there were no known additional risk
`factors. Use caution with these agents and consider additional monitoring when concomitant
`use is medically necessary
`
`Thrombocytopenia
`- In EMILIA, the incidence of a Grade 3 thrombccytcpenia was 14.5% in the KADCYLA-treated
`group and 0.4% in the comparator group {overall incidence 31.2% and 3.3%. respectively}
`- Monitor platelet counts prior to initiation of KADCYLA and prior to each KADCYLA dose.
`Institute dose modifications as appropriate
`
`Neurotoxlolty
`- In EMILIA, the incidence of a Grade 3 peripheral neuropathy was 2.2% in the KADCYLA-
`treated group and 0.2% in the com parator group (overall incidence 21.2% and 13.5%,
`respectively]
`- Monitor for signs or symptoms of neurotoxicity. KADCYLA should be temporarily discontinued
`in patients experiencing Grade 3 or 4 peripheral neuropathy until resolution to 5 Grade 2
`
`IMMUNOGEN 2336, pg. 3
`Phigenix v. Immunogen
`IPR2014-00676
`
`IMMUNOGEN 2336, pg. 3
`Phigenix v. Immunogen
`IPR2014-00676
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`

`

`HER: Testing
`* Detection of HE Ft2 protein overexpression or gene am plitication is necessary for selection of
`patie MS appropriate for KADCYLA. PBI'iClrlTl using FDA-approved iE$t$ by laboratones with
`demonstrated proficiency
`Extravaeation
`
`- In KADCYLA clinical studies, reactions secondary to extravasation have been observed and
`Iwere generally mild. The infusion site should be closely monitored for possible subcutaneous
`infiltration during drug administration. Specific treatment for KADCYLA extravasation is
`unknown
`
`Nursing Mothers
`' Discontinue nursing or discontinue KADGYLA. taking into consideration the importance oi the
`drug to the mother
`Adverse Reactions
`
`' The ITIOGI ¢CIITIITIOFI {frequency 33-25%} adverse drug reactions {ADE} across clinical trials with
`KADCYLA were nausea, fatigue, musculoslceletal pain, hemorrhage, thrombocytopenia,
`increased transaminases. headache, constipation. and epistaxis. In EMILIA, the most
`common NCI—CTCAE (version 3] a Grade 3 ADFts [freque ncy >293} were thrombocytopenia,
`increased transaminases. anemia. hypoiralemia. peripheral neuropathy. and fatigue
`
`You are encouraged to report side effects to Genentech and the FDA. You may contact
`Genentech by calling 1-338-335-2555. You may contact the FDA by visiting
`wwwfdagovimedwatch or calling 1—am—FDA—1 033.
`
`Please download the full Prescribing Information for additional important safety
`information, including Boxed WARNINGS.
`
`For more information on KADCYLA, visit KADCYLA.com.
`
`References: 1. KADCYLA Prescribing Information. Genentech, Inc. July 2014. 2. Verma 5,
`Miles D. Gianni L, et al; EMILIA Study Group. Trastuzu mat: emtansine for HERB-positive
`advanced breast cancer [published correction appears in N Engf J Med. 2013;363:2442]. N Eng:
`J Med. 2012;36?:1?33-1?91 and Supplementary Appendix.
`
`TDMDD02192?UI {DWI I1-]I
`
`
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`
`IMMUNOGEN 2336, pg. 4
`Phigenix v. Immunogen
`IPR2014-00676
`
`IMMUNOGEN 2336, pg. 4
`Phigenix v. Immunogen
`IPR2014-00676
`
`

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`6mm“
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`IMMUNOGEN 2336, pg. 5
`Phigenix v. Immunogen
`IPR2014-00676
`
`IMMUNOGEN 2336, pg. 5
`Phigenix v. Immunogen
`IPR2014-00676
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