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`C O 2
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`005 ASCO Annual Meeting Proceedings
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`West-Ward Pharm.
`Exhibit 101 1
`Page 001
`
`West-Ward Pharm.
`Exhibit 1011
`Page 001
`
`

`

`Developmental Therapeutics: Molecular Therapeutics
`
`21 55
`
`Publication only
`3,093
`nteiit and effective i=-giycuitrntein IPEP) "'*'""“"
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`that can lie administeiotlasgfely with chernotheral1l'- _-‘LL52 .i'd9_-‘l_E'_f.i‘-‘.§- 3- F3”-
`""'- Edsertir. o. Draper. C. Chen.
`ii. irotier. F-
`-‘3-‘*’i'5- W’ 9- H33’ 5‘ Sam’
`A 3 Faro; iviH/ivci, Bethesda. MD
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`w
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`[X
`oncerns. We report our
`R9576). closed prematurely due to toxtclhl 0 Methods: Patients with
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`””"‘°l0ri' orui-:3:sijtlliguddfendcortical cancer {M39} .'e.°eNe-d ta-miuldar Dd
`dais 1 8. 3 with a 96-hour infusion of doxorubitiln‘ wnmstlne’ an
`F-'l°lJ0si'de with initotane {X-MAVE) We'll 21 da3"5' Patients with rle'"faCt'0w
`irarian, cervical St lung cancer received taritl‘-‘ma’ "“"th '3 dc."°.eta”e ;n
`em)’ 21 “alts. Stud!’ liarticipants had two "‘-""Tc-sestarnibi sc|an|.t d to
`a"“Vll¥ curves were generated and areas under the curve ca clu ‘ail is her
`c°”‘|3a"e """"Tc—sestamibi accumulation at baseline to thatb f
`a
`d
`tafittuidar. Rhodainine eflltix from CD56+ cells was measured .3 Ore alih
`aha’ ialifluidar to assess Pgp inhibition. llesults: To deal?‘ 15 panama ii"
`400 have received rt cycles of x.it-irtvc. and 16 patients with g"*'c'|'“"3;
`°°T\‘it:al or lung cancer have received 55 cyc|95 0', dncetafilé .,,'§'..,".,.,.
`"°”-hematologic toxicities (ll of cycles) observed with X-liil_
`(2) d_
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`abdominal painlconstipation (4) arthralgla (4). nau_seai‘vomitinB
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`ihea l U. esoflhagitis l 1 l. fatigue l6}. hand-toot reaction (1 l. and WDODB 73'
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`21': (3). those with docetaitet include. diarrhea ill
`iggmjbi accumulation
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`'.ncreasie|:l31.:I4.1‘I3at(cr3i'2?3a‘ll? icsojnfpirijrddaiiiragriiean increase of ._l06%Qll'lli1totll:f|ETi
`in
`°l 3 Patients with il\CC whose lesions could be V'9”a"z"'d'
`iuagr: ginon
`f°' "19 10 such patients with ovarian. cervical or lUf'.g cancer 5d g d
`Rhociamine effluit from CD56+ cells assayed i" 30 Pamms was re Uiag hy
`3 ""“-3'1 of 85% after tariquidar and wa
`5i_3'"ed we" after;
`d‘
`Phafmacokinetic sampling before and after tarICl““i"". has been 98 -tom}:
`Conciusinns: Tariquidar is a potent and highly effective Pen lfllllbtl or do
`can '33 administered safely with a combination of d°’,“’mb'cinii s llpftia E
`I:
`.
`and iiincristine or with docetaxel. The elficaclf l" F'at'e"l5 W"
`re fa
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`°"°Ers continues to be evaluated.
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`h._5ym;;g.labo Researcti. Matvern.
`ginffielabo Research. fl-falvern. PA: 3399
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`271425 is a novel cytotoxic
`“‘lflteractiTnhge £:h;?'lJia:t|'tlti1lr1Jn:
`liiiloaadgsoectrum of antitumor activity In
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`ial aims to determine
`micral "Mme tumor modem’ This ch" hour single intravenous dose
`repeamd
`d D
`1 week rest.
`to determine the
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`e asses‘ “5 Dharmacokinetic piofile. Methods: A modiliedof gggrmzs is
`Pliiglc min" d53lE"I i5 being Used‘ A Single intravenimiifedofif 1 week rest
`in a
`m'“'5‘EFei:| over l-hourweeltly for 2 weeks, tol dthe rabbit model. ElTc
`variety of rgfractcry solid tumors. Of note.
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`Tli(i:ongE't'°|'i. related to Cinax. hi‘-‘5 been reported assegsntent with serial
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`from the drugs short nail-life (6.7 "V10 Systizatf i versus Day 8.
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`‘-‘Elven as assessed by Cmax and Cii._V3]”e%::g|usions: Preliminary
`Ulsea
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`ed in 3 patients.
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`rlayao
`use has been observ
`RZHAZ5 admlT'l1SiBTl‘2d atsplit.
`wi_.ek|y“r;:ils ongoing study sugE95l5 th2:l..|?“_I|af_jue exposure without signifi-
`cgnIlm“_ci‘-{:3 will likely allow greater C
`
`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`Publication only
`3094
`Phase I iiliarrtiacoliinetit:-pl-iarmacodynamii: trial of weekly MS-275. an oral
`histpne doaoetylase inhibitor. L A. Do.-toga G. Ryari. M‘. Acharya. E.
`Chung. J. Trcpef. K. Maynard. E. Sausvilte. A. Murgo. G. Melitta, B. Conley;
`National Cancer fnsfitufe, Bethesda. MD
`is a histone
`Background: MS-2}'5. a synthetic benzairiide derivative.
`deacetylase IHDAC)
`inhibitor with in vitro at
`in vivo antitumor activity.
`Based on our q2 week closing results. we eiiplored rnaximurn tolerable dose
`(MTD) 8: dose limiting toxicity (Dl.Tl for a weekly schedule with 2 oral
`formulations 8: 2 administration conditions. Methods: MS—2I-'5 tincoated
`("A" with meat} or coated l“B" lasting) tablets were given weekly x4 qt}
`weeks to patients (pie) with advanced malignancy & P5‘-2. Ll-Ts£2.5lt
`normal. adequate hernatopcietic tit renal function. & normal resting MUGA.
`Pharmacol-tt'i1eti'cs(F'K) (validated LCMS method) & histone H3 acetylation
`(H3Ac) in peripheral blood mononuclear cells tPBlvlC) (lHC image analysis
`and novel flow cytometric assay for protein acetylationl were assessed.
`Results: 13 pts. ECOG PS =1 it]-2) received median of l (1v—4J course. 4
`“i°l" (4-6 mgi'm2l cits & ? "B" l2-4 rngi'rn2l pts were evaluable for cycle 1
`toxicity lCTC v2.0). "A" grade 3 toxicities were hypoalburninemia. neutro-
`penia St vomiting. On "B“. 2 pts had DLT at 4 mgI'm2. one with grade 4
`dyspneaitgrade 3 pleuritic pain 8. dyspepsia at one with right heart failure.
`diarrhea & hypoalbuminemia. Grade 1—2 toxicities in /1 pt for A or B were
`thrornbocytopenia. fatigue. hyperglycemia. taste disturbance. hypoalbumin—
`emia, hypocalcemia. hypornagnesemia. hypophosphatemia,
`leucooenia.
`neutrdpenia. nausea. anorexia, headache. dyspepsia. flatulence. rnyalgias
`St insomnia. Enrollment is ongoing on “B" 2 mgi‘m2 fasting. Median Trnait
`was 0.5h lU.5— fihl. At 4 mgi'm2. mean Cmax was 38.2 ngfmL (14--71
`nymLl in "El" vs 4.8 ngJmL l4-- 6 ngi'mi.l in "A. Mean AUC at 2. 4. & 6
`mgi‘m2: I90. 284. & 358 ng"'hi'nlL. respectively. PBMC H3Ac was seen at
`all dose levels. 3 pts had stable disease. 2 at 4 mgi’m2 (colon. CTCL,‘ & lot
`2 mg.tm2 tCTCLl. conclusions: The MTD for coated MS—2?5 given fasting
`on this schedule was exceeded at 4 mgi‘m2 p.o. weekly x4 q6 weeks. AUC
`increased with dose. Drug-related hyperaceiylalion was observed.
`
`Publication only
`30%
`A phase II trial of tomsiroliriuis in metastatic neurooiitlocrioe carcinomas
`{REDS}. _l_._Diifli. L. Le. 0. Salmon. J. Kortrnansfry. W. Kacha. D. Sirigli.
`G.
`ii’. Pond. J. M. Perafba. J. Dancey. L. L. Stu; Princess Margaret Hosp
`Phase ti‘ Consortium, Toronto. ON. Canada; Memorial Sloari-Kettering
`Cancer Ctr. New York. NY: Univ of Cfii'ca.go, Chicago. ti; Johns Hopkins
`Univ Sch of Medi'cr'ne. Baffirnore. MD; National Cancer frisfifiite. Bethesda.
`MD
`
`Background: N Ecs are a varied group of endocrine neoplasms characterized
`by neurosecrefory granules and cell surface markers. Except for islet cell
`carcinomas. NECs are resistant
`to conventional cytotoxics. Hormonal
`therapy such as somatostatin analogs or local therapies such as hepatic
`resection or arterial ernbolization are generally delivered to palliate symp-
`toms. Temsiroliirius is a novel n'iTOR inhibitor that downregulates cascades
`activated by loss of the tumor suppressor protein PTEN. a defect reported in
`moderately differentiated NECs. Due to the lack of effective systemic
`therapy for NECs. loss of PTEN detected in some cases. and a report of a
`partial response in this tumor type from phase I
`trials. a mu1ti—cerilre
`2-stage phase II
`trial
`in NECS was conducted. Methods: Patients were
`eligible if they demonstrated 25% increase in tumor volume. clinical
`deterioration or new tumor focus in the last 6 months. Temsirolinius 25 mg
`was administered intravenously over 30 minutes on a weekly basis. Results:
`To date, 23 patients {ms} with progressive NECs ltave been enrolled with
`the following demographics from 18 pts with baseline data: median
`age: .35. raitg.-3:36-68. M:F=9-.9. ECOG 0:1-2* 8:91. and 11 pts had
`prior chertiotlierapy. Toxicity inforriiatiori is available from 15 pts in 50 four
`weekly cycles. The most frequently encountered grade 3-4 toxicities
`expressed as ‘it. of
`treatment cycles are: hypophosphatemia (14%).
`hyperglycemia {10%l. cough (10%-l. hypokaleiiiia (8%). hyperchoiestero|—
`eiriia l8%l. and hypertension (8%). The most frequent toxicities consider‘
`itig all grades are: fatigue (86%). anemia t}'6%l and lymphopeiiia [70%l.
`Among 15 pts evaluable for response thus far. to have achieved prolonged
`stable disease (range: 3—l'l cycles).
`including 1 pt with a 24% ttiinoi
`shrinkage by REClST criteria after 4 cycles. and 2 pts who have el(|JEfiv
`enced significant clinical benefit and are on cycles 9 and i 1. respectively.
`Levels of pi'OS6kinase in peripheral blood mononuclear cells at 24 hours
`post
`treatment have not shown correlation with cfiiiical outcome in the
`majority of pts. Markers of cell cycle inhibition and apoptosis in paired
`tumor biopsies will be reported. conclusions: Temsirol iinus appears to have
`antitumor activity in NECS, study accrual is ongoing.
`
`West-Ward Pharm
`Exhibit 101 1
`
`West-Ward Pharm.
`Exhibit 1011
`Page 002
`
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