REF PRODUC DATE
`
`DESCRIPTION
`
`SERI PROTOCOL SUBMISSION TYPE
`
`66,279 RAD 001C 02126/2007 Novartis Pharmaceuticals Corporation authorizes the FDA 299
`to refer to IND 66,279 RAD001 (everolimus) Tablets in
`support of an lnvestigational New Drug Application (IND)
`that will be filed by Bert O'Neil , M.D. (PS)
`
`66,279 RAD 001 C 02126/2007 Novartis Pharmaceuticals Corporation authorizes the FDA 300
`to refer to IND 66,279 RAD001 (everolimus) Tablets in
`support of an lnvestigational New Drug Application (IND)
`that will be filed by Srdan Verstovsek, M,D .. Ph.D. (PS)
`
`66,279 RAD 001C 0212612007 Novartis Pharmaceuticals Corporation authorizes the FDA 301
`to refer to IND 66,279 RAD001 (everolimus) Tablets in
`support of an lnvestigational New Drug Application (IND)
`that will be filed by Johanna Bendell, M.D. (PS)
`
`66,279 RAD 001C 0212212007
`
`FDA LETTER Responses to the November 6, 2006, serial
`number 252, request for SPA.
`
`66,279 RAD 001C 0212212007
`
`PHH02007CA02219; follow-up (PS)
`
`66,279 RAD 001C 0212212007
`
`This Annual report covers the period December 25, 2005
`through December 24, 2006 (PS)
`
`66,279 RAD 001C 02/20/2007
`
`Email from FDA responding to Novartis' question regarding
`the PPSR being submitted.
`
`66,279 RAD 001C 02119/2007
`
`Proposed Pediatric Study Request submiited for the
`treatment of refractory cancers in a pediatric population
`(ages 3-16) (Protocol No. CRAD001C2244) (PS)
`
`66,279 RAD 001C 02119/2007
`
`New investigators to Study CRAD001C2114,
`CRAD001C2240 and CRAD001C2241 (PS)
`
`66,279 RAD 001C 02119/2007
`
`This annual report covers the period November 27, 2006
`through November 26, 2007. (PS)
`
`66,279 RAD 001C 02115/2007
`
`PHBS2006AT07989; follow-up (PS)
`
`66,279 RAD 001C 0211312007 At this time, Novartis is submitting an IND amendment to
`provide updated information on the manufacturing sites,
`stability programs, and other CMC changes. The summary
`of changes and the updated IND sections are included in
`this submission (PS)
`
`66,279 RAD 001C 02/09/2007 PHH02007CA02219; follow-up (PS)
`
`66,279 RAD 001C 0210912007 New Protocol RAD001 C2242 entitled: "An open-label,
`multicenter Phase 1 study investigating the combination of
`RAD001, cetuximab and irinotecan as second-line therapy
`after FOLFOX (or XELOX) plus bevacinunab (if given as
`part of local standard practice) in patients with metastatic
`colorectal adenocarcinoma" (PS)
`
`296
`
`297
`
`294
`
`295
`
`547
`
`293
`
`292
`
`290
`
`291
`
`66,279 RAD 001C 0210812007 Novartis Pharmaceuticals Corporation authorizes FDA to
`refer to IND 66279 for RAD001 (everolimus) in support of an
`lnvestigational New Drug Application (IND) that will be filed
`by Dr. Mark Stein (PS)
`
`289
`
`66,279 RAD 001C 02108/2007 PHH02007CA02219; follow-up (PS)
`
`66,279 RAD 001C 02107/2007 PHH02007CA02219 (PS)
`
`288
`
`287
`
`66,279 RAD 001C 02106/2007 Novartis Pharmaceuticals Corporation authorizes the FDA 285
`to refer to IND 66,279 RAD001 (everolimus) Tablets in
`support of an tnvestigational New Drug Application (IND)
`that will be filed by Daniel George, MD (PS)
`
`Other
`
`Other
`
`Other
`
`Other
`
`Safety Report
`
`Annual Report
`
`Other
`
`Other
`
`New Investigator
`
`Annual Report
`
`Safety Report
`
`CMC Amendment
`
`Safety Report
`
`New Protocol
`
`Other
`
`Safety Report
`
`Safety Report
`
`Other
`
`
`
`

`
`REF PRODUC DATE
`
`DESCRIPTION
`
`SERI PROTOCOL SUBMISSION TYPE
`
`66,279 RAD 001 C 02106/2007 Novartis Pharmaceuticals Corporation authorizes the FDA 286
`to refer to IND 66,279 RAD001 (everolimus) Tablets in
`support of an Investigations! New Drug Application (IND)
`that will be filed by Jorae A. Ciarcia. MD (PS)
`
`Other
`
`66,279 RAD 001 C 0210512007 New investigators to Study CRAD001 C2239 and
`CRAD001C2240 (PS)
`
`66,279 RAD 001C 02101/2007 PHH020048E07879; follow-up (PS)
`
`66,279 RAD 001C 01/29/2007 This submissions contains copies of the materials sent on
`January 25, 2007, serial number 280 (PS)
`
`66,279 RAD 001C 01/26/2007 Email to FDA informing them that the materials sent via
`email have been sent directly to them instead of the central
`document room.
`
`66,279 RAD 001C 01/26/2007 PHH02006US22076; follow-up (PS)
`
`66,279 RAD 001C 01/25/2007 PHH02007US00556; follow-up (PS)
`
`66,279 RAD 001C 01/19/2007 PHH02006US22076 (PS)
`
`284
`
`283
`
`282
`
`281
`
`279
`
`278
`
`66,279 RAD 001C 01/18/2007 New investigator/Sub investigator to Study CRAD001 C2111 276
`(PS)
`
`New Investigator
`
`Safety Report
`
`General Correspondence
`
`Response to FDA Request
`
`Safety Report
`
`Safety Report
`
`Safety Report
`
`New Investigator
`
`66,279 RAD 001C 01/18/2007 PHH02007US00556 (PS) .
`
`277
`
`Safety Report
`
`66,279 RAD 001C 01/17/2007 Email to FDA informing them of the upcoming Novartis FDA
`CRADA meeting.
`
`66,279 RAD 001C 01/16/2007 Email from FDA replying to the meeting cancellation of the
`January 18, 2007 Type A meeting.
`
`Other
`
`Other
`
`66,279 RAD 001C 01/16/2007 New investigator to Study CRAD001C2239 and
`CRAD001C2325. New investigators to Study
`CRAD001C2240 (PS)
`
`66,279 RAD 001C 01/09/2007 This correspondence is to provide the FDA with Novartis'
`questions for the Type A meeting which is scheduled for
`January 18, 2007 (ES)
`
`275
`
`New Investigator
`
`General Correspondence
`
`66,279 RAD 001C 01/03/2007 Email to FDA containing serial number 274, an addendum
`to the briefing book (ES)
`
`General Correspondence
`
`66,279 RAD 001C 01/03/2007 The addendum the the briefing book contains simulation
`data which is highly relevant to the planned discussions and
`the conclusions are supportive of the Novartis position as
`stated in the protocol. Please note that this submission in
`REDI only contains the cover letter and 1571, as this is all
`we received for archiving). (PS)
`
`274
`
`Other
`
`66,279 RAD 001C 01/01/2007 Email from FDA responding to Novartis' questions regarding
`the FDA information request for the simulation methods.
`
`Other
`
`66,279 RAD 001C 12128/2006 PHH02006FR20729; Follow-up
`
`273
`
`Safety Report
`
`66,279 RAD 001C 1212212006 Email from FDA with responses to Novartis' questions
`regarding protocol CRAD001C2325
`
`66,279 RAD 001C 1212212006 PHH02005DE16006; Follow-Up
`
`66,279 RAD 001C 12121/2006 New investigator to Study CRAD001C2239 and
`CRAD001C2241, new investigators to Study
`CRAD001C2240 (PS)
`
`66,279 RAD 001C 12121/2006 PHH02006FR20729; Follow-up
`
`272
`
`271
`
`270
`
`Other
`
`Safety Report
`
`New Investigator
`
`Safety Report
`
`
`
`

`
`REF PRODUC DATE
`
`DESCRIPTION
`
`SERI PROTOCOL SUBMISSION TYPE
`
`66,279 RAD 001C 12121/2006 PHBS2006ES19190; Follow-Up
`
`66,279 RAD 001C 12121/2006 PHBS2006ES19166; Follow-Up
`
`66,279 RAD 001C 12120/2006 Amendment No. 2 to Protocol CRAD001 C2239 (PS)
`
`66,279 RAD 001C 12118/2006 PHH02006FR20566; Follow-Up
`
`66,279 RAD 001C 12118/2006 PHH020061T15311; Follow-Up
`
`269
`
`268
`
`267
`
`266
`
`265
`
`66,279 RAD 001C 12113/2006 Novartis Phannaceuticals Corporation authorizes the FDA 264
`to refer to IND 66,279 RAD001 (everolimus) Tablets in
`support of an lnvestigational New Drug Application (IND)
`that will be filed by Gabriela Chiorean, MD (PS)
`
`66,279 RAD 001C 1211212006
`
`In response to FDA request the email contains the
`questions q posed in BB submitted with SPA for
`CRAD001C2325 (RAD001 in Carcinoid IND66,279) on Nov
`6,2006(Seriai252)(ES)
`
`66,279 RAD 001C 1211212006 PHH02006US17466; follow-up (PS)
`
`66,279 RAD 001C 1211212006 New investigator to Study CRADOO 1 C2111,
`CRAD001C2239, and new investigators to CRAD001C2241
`(PS)
`
`66,279 RAD 001C 12/08/2006 PHH020061T15311; follow-up (PS)
`
`263
`
`262
`
`260
`
`66,279 RAD 001C 12108/2006 This correspondence is to infonn the FDA of the transfer of 261
`specific obligations to a contract research organization for
`clinical drug supply management of selected sites in
`protocol CRAD001C2240 (PS)
`
`Safety Report
`
`Safety Report
`
`Change In Protocol
`
`Safety Report
`
`Safety Report
`
`Other
`
`Response to FDA Request
`
`Safety Report
`
`New Investigator
`
`Safety Report
`
`General Correspondence
`
`66,279 RAD 001C 12107/2006 New investigators to Study CRAD001C2239 (PS)
`
`259
`
`New Investigator
`
`66,279 RAD 001C 12107/2006 Fax from FDA containing the Medical imaging responses to
`serial number 249.
`
`Other
`
`66,279 RAD 001C 12/06/2006 PHH02006US11747; follow-up (PS)
`
`258
`
`Safety Report
`
`66,279 RAD 001C 11/21/2006 Email from FDA confirming the postponement of the
`November 27, 2006teleconference to January 18, 2007.
`
`Other
`
`66,279 RAD 001C 11116/2006 Email response to the FDA request for a copy of the draft
`IRC charter for CRAD001 C2239 protocol.
`
`Response to FDA Request
`
`66,279 RAD 001C 11115/2006 Amendment No. 1 to Protocol RAD001C2235 (PS)
`
`66,279 RAD 001 C 11/09/2006 PHH02004US12965; follow-up (PS)
`
`257
`
`256
`
`Change In Protocol
`
`Safety Report
`
`66,279 RAD 001C 11/07/2006 This submission contains RAD001C Investigator's Brochure 253
`Edition 5 (PS)
`
`Clinical Information Amendr
`
`66,279 RAD 001 C 11/07/2006 New investigator to Study CRAD001 C2206 (PS)
`
`66,279 RAD 001C 11107/2006 PHH02006US17466; Follow-Up (PS)
`
`66,279 RAD 001C 11/06/2006 Request for special protocol assessment for Study
`CRAD001C2325 (PS)
`
`66,279 RAD 001C 10/31/2006 PHH02006US17466 (PS)
`
`254
`
`255
`
`252
`
`251
`
`66,279 RAD 001C 10/24/2006 Briefing Book is being submitted in preparation for the Type 249
`A meeting to gain clarification on FDA's responses , provide
`clarification on Novartis position and ensure agreement on
`any additional modifications which may be required to allow
`for a positive agency determination regarding protocol
`CRAD001 C2240 and allow the study to proceed (PS)
`
`New Investigator
`
`Safety Report
`
`Other
`
`Safety Report
`
`Briefing Book
`
`
`
`

`
`REF PRODUC DATE
`
`DESCRIPTION
`
`SERI PROTOCOL SUBMISSION TYPE
`
`66,279 RAD 001C 10/24/2006 PHBS2006ES15520; follow-up (PS)
`
`250
`
`Safety Report
`
`66,279 RAD 001C 10/2312006 Email responding to FDA that Novartis acknowledges
`receipt of the e-mail and the proposed date of the meeting
`for November 27th 2PM.
`66,279 RAD 001 c 10/2312006 Email to FDA regarding the number of copies needed of the
`briefing book and the meeting date of November 10, 2006
`for the Type A meeting.
`
`Other
`
`Other
`
`66,279 RAD 001C 10/2312006 PHH02006US11747; follow-up (PS)
`
`248
`
`Safety Report
`
`66,279 RAD 001C 1012312006 Novartis Pharmaceuticals Corporation authorizes the FDA 247
`to refer to IND 66,279 RAD001 (everolimus) Tablets in
`support of an lnvestigational New Drug Application (IND)
`that will be filed by Andrew X. Zhu, MD, PhD (PS)
`66,279 RAD 001 c 10/20/2006 Email response to the FDA request for an electronic copy of
`the Type A meeting request.
`
`Other
`
`Request for FDA Meeting
`
`66,279 RAD 001C 10117/2006 PHBS2006S15520; Follow-up (PS)
`
`246
`
`Safety Report
`
`66,279 RAD 001C 1011312006 Novartis Pharmaceuticals Corporation authorizes the FDA 245
`to refer to IND 66,279 RAD001 (everolimus) Tablets in
`support of an lnvestigational New Drug Application (IND)
`that will be filed by Barbara Burtness, MD (PS)
`
`Other
`
`244
`
`Request for FDA Meeting
`
`Safety Report
`
`New Investigator
`
`Safety Report
`
`Safety Report
`
`Other
`
`New Investigator
`
`New Protocol
`
`Other
`
`New Protocol
`
`66,279 RAD 001C 10/09/2006 Type A meeting request to gain further clarification on the
`responses received by the FDA, particularly for questions 3,
`7 and 11. More specifically Novartis wishes to identify any
`additional modifications to the proposed pivotal study,
`analysis plan and independent radiological review charter
`necessary to adequately meet the requirements for a
`regulatory submission of phase Ill protocol CRAD001C2240
`data in support of approval of RAD001 for the treatment of
`patients with metastatic renal cell carcinomas who have
`
`66,279 RAD 001C 10/0612006
`
`PHH020061T15311 (PS)
`
`66,279 RAD 001C 10/0312006
`
`New investigator to Study No. RAD001C2239 (PS)
`
`66,279 RAD 001C 10/0312006
`
`PHH020061T15311 (PS)
`
`66,279 RAD 001C 09129/2006
`
`PHH02006lT09039; Follow Up (PS)
`
`66,279 RAD 001C 09127/2006
`
`Addressing Issues raised per September 26, 2006 phone
`call noting discrepancies between information Novartis
`submitted and the FDA website so that Entry
`506-0814195-3 can be released. (PS)
`
`66,279 RAD 001C 09/25/2006 New investigator to Study No. RAD001C2206 and new
`investigators to Study No. RAD001 C2239 (PS)
`
`66,279 RAD 001C 09119/2006 New Protocol RAD001J2101 entitled: "A phase lb study
`investigating the combination of AD001 with trastuzumab
`and paclitaxel in patients with HER2-overexpressing
`metastatic breast cancer" (PS)
`
`66,279 RAD 001C 0911512006 FDA LETTER response to SPA for CRAD001C2240 (PS)
`
`243
`
`241
`
`242
`
`240
`
`239
`
`238
`
`66,279 RAD 001C 0911312006 New Protocol RAD001C2114 entitled, "A two-step phase 1 236
`study investigating the combination of RAD001 with
`carboplatin, paclitaxel and bevacizumab in non-small-cell
`lung cancer (NSCLC) patients not treated previously with
`systemic therapy (PS)
`
`
`
`

`
`REF PRODUC DATE
`
`DESCRIPTION
`
`66,279 RAO 001C 09/1312006 New Protocol RAD001 C2116 entitled: • A phase lb study
`investigating the combination of RAD001 .with cisplatin and
`etoposide in patients with extensive-stage small-cell lung
`can'?8r not previously treated with chemotherapy" (PS)
`
`66,279 RAO 001 C 09/07/2006 TELECON with FDA on September 7, 2006 to discuss the
`request for ane e-copy of the CRAD001C2240 SPA and the
`timelines for FDA review/response of Oncology PPSR (PS)
`
`66,279 RAD 001C 09/07/2006 Email regarding the request from FDA for an electronic copy
`fo the SPA for protocol CRAD001C2240 (PS)
`
`66,279 RAD 001C 0813112006 PHH02006US02640; follow-up (PS),
`
`66,279 RAO 001C 08131/2006 Novartis Phannaceuticals Corporation hereby authorizes
`the FDA to refer to IND 66,279 RA0001 (everollmus)
`Tablets in support of an lnvestigational New Drug
`Application (IND) that will be filed by John D. Hainsworth,
`M.D. (PS)
`
`SERI PROTOCOL SUBMISSION TYPE
`
`237
`
`New Protocol
`
`Memo of Record (telephone
`report)
`
`Response to FDA Request
`
`234
`
`235
`
`Safety Report
`
`Other
`
`66,279 RAO 001 C 08/29/2006 New investigator to Study No. CRAD001C2206 (PS)
`
`233
`
`New Investigator
`
`66,279 RAO 001 C 0812312006 Email response to FDA request for TOC and and electronic
`copy of the 11 protocol specific questions listed in section 5
`of the briefing book submitted on July 28, 2006 (PS)
`
`66,279 RAD 001 C 08122/2006 New Protocol, RA0001C2241 entitled, "A single enn,
`multicenter phase ti study of RA0001 in patients with
`metastatic colorectal adenocarcinoma whose cancer has
`progressed despite prior therapy with an anti- EGFR
`antibody (if appropriate), bevacizumab, fluoropyrimidine,
`oxaliplatin, and irinotecan- based regimens (PS)
`
`Response to FDA Request
`
`231
`
`New Protocol
`
`66,279 RAD 001C 08/18/2006 PHH02006BE00473; follow-up (PS)
`
`66,279 RAD 001C 08/1812006 PHH02006DE09301; follow-up (PS)
`
`66,279 RAO 001C 08/18/2006 PHH02006US11747; follow-up (PS)
`
`66,279 RAO 001C 08/17/2006 PHH02006US11747; follow-up (PS)
`
`66,279 RAD 001 C 08/16/2006 PHH02006BE00473 (PS)
`
`66,279 RAD 001 C 08/15/2006 PHH02006US11747 (PS)
`
`66,279 RAD 001C 08/04/2006 New investigator to Study CRAD001C2239 (PS)
`
`66,279 RAD 001C 07128/2006 Request for special protocol assessment for Study
`CRAD001C2240 (PS)
`
`66,279 RAD 001C 07/28/2006 PHH02006DE09652; follow-up (PS)
`
`66,279 RAD 001C 0712712006 Amendment No. 2 to Protocol CRAD001JC2222 (PS)
`
`66,279 RAO 001C 0712612006 PHH02006CA03486; follow-up (PS)
`
`66,279 RAO 001C 07125/2006 PHH02006DE09859; follow-up (PS)
`
`66,279 RAO 001C 07/21/2006 Documentation FDA position: Pediatric Exclusivity
`requirements NOA submission for active moiety.
`
`66,279 RAO 001C 07/21/2006 PHH02006DE09652; follow-up (PS)
`
`66,279 RAO 001C 07/2012006 PHH02006DE09652; follow-up (PS)
`
`66,279 RAO 001C 07120/2006 PHH020061T09039; follow-up (PS)
`
`228
`
`229
`
`230
`
`227
`
`226
`
`225
`
`224
`
`223
`
`222
`
`221
`
`220
`
`219
`
`218
`
`215
`
`216
`
`Safety Report
`
`Safety Report
`
`Safety Report
`
`Safety Report
`
`Safety Report
`
`Safety Report
`
`New Investigator
`
`Other
`
`Safety Report
`
`Change In Protocol
`
`Safety Report
`
`Safety Report
`
`Other
`
`Safety Report
`
`Safety Report
`
`Safety Report
`
`
`
`

`
`REF PRODUC DATE
`
`DESCRIPTION
`
`SERI PROTOCOL SUBMISSION TYPE
`
`66,279 RAD 001C 07/20/2006 PHH02006DE09301; Follow Up (PS)
`
`66,279 RAD 001C 07/1912006 PHH02006DE09652; follow-up (PS)
`
`66,279 RAD 001C 07/17/2006 PHH020061T09039; follow-up (PS)
`
`66,279 RAD 001C 07/11/20Q6 At the request of the principal investigator for the study,
`Novartis Pharmaceuticals Corporation is hereby amending
`this letter to reflect a change in principal investigator for the
`study. Novartis authorizes the Food and Drug
`Administration to refer to IND 66,279 RAD001 (everolimus)
`Tablets in support of an lnvestigational New Drug
`Application (IND) that will be filed by Alice Elizabeth
`Guardino, M.D., Ph.D. (PS)
`
`217
`
`214
`
`213
`
`212
`
`Safety Report
`
`Safety Report
`
`Safety Report
`
`Other
`
`203
`66,279 RAD 001C 07/0712006 FDA LETTER (email) FDA Response to questions on
`briefing book for Type A Meeting scheduled for July 11,2006
`(CRAD001C2239 SPA follow-up).
`
`66,279 RAD 001C 07/0712006 PHH02006DE09652 Follow Up
`
`66,279 RAD 001C 07/07/2006 Referencing General Correspondence letter of Authorization
`SN156. Novartis is amending this letter to reflect a change
`in address and study title.
`
`66,279 RAD 001C 07/0512006 PHBS2006AT07989 Follow Up
`
`66,279 RAD 001C 06127/2006 PHBS2006AT07989 Follow up
`
`66,279 RAD 001C 06/27/2006 PHH02006DE09859 Follow Up
`
`66,279 RAD 001C 06127/2006 PHNU2006DE02164 (PS)
`
`66,279 RAD 001C 06122/2006 Referencing General Correspondence Letter of
`Authorization SN 157. Novartis Pharmaceutical Corporation
`is hereby amending this letter.
`
`66,279 RAD 001C 06121/2006 PHH02006DE09301 Follow Up
`
`210
`
`209
`
`206.
`
`207
`
`208
`
`204
`
`66,279 RAD 001C 06/2012006 Type A meeting briefing book to support the discussion for a 203
`special protocol assessment for CRAD001C2239 submitted
`on April 3, 2006 (Serial No. 183). (PS)
`
`66,279 RAD 001C 06/1912006 Referencing an authorization to the FDA by Novartis to
`referto IND 66,279 RAD001.
`
`66,279 RAD 001C 06/1912006 Referencing an authorization to the FDA by Novartis to refer
`to IND 66,279 RAD001.
`
`Other
`
`Safety Report
`
`Safety Report
`
`Safety Report
`
`Safety Report
`
`Safety Report
`
`Safety Report
`
`General Correspondence
`
`Safety Report
`
`Briefing Book
`
`General Correspondence
`
`General Correspondence
`
`66,279 RAD 001C 06/.1612006 PHH020061T09039 Follow Up
`
`200
`
`Safety Report
`
`66,279 RAD 001C 06/1612006 Email responding to the FDA request for the questions
`which will be presented in the briefing document for the FDA
`Type A meeting scheduled for July 11, 2006.
`
`66,279 RAD 001C 06/1412006 PHH020061T07069 Follow Up
`
`198
`
`66,279 RAD 001C 06/13/2006 7 Day Safety Report PHH020061T09039 (PS)
`
`66,279 RAD 001C 06/0512006 Request for Type A Meeting to gain darification on
`responses and modifications to the analysis regarding
`treatment with RAD001 alone or in combination with
`Sandostatin for patients with NET, who failed treatment with
`cytotoxic chemotherapy
`
`Other
`
`Safety Report
`
`Safety Report
`
`Request for FDA Meeting
`
`
`
`

`
`REF PRODUC DATE
`
`DESCRIPTION
`
`SERI PROTOCOL SUBMISSION TYPE
`
`66,279 RAD 001 C 06/02/2006 Reference is made to IND 66,279 Annual Report for
`RAD001 dated February 24, 2006 regarding the clinical
`review reported to the FDA for a Phase II Study of
`RAD001C
`
`66,279 RAD 001C 05/30/2006 Protocol C2111 Amendment 1 and Protocol C2206
`Amendment 5. (PS)
`
`66,279 RAD 001C 05/23/2006 PHBS2006ES06880 Follow Up
`
`66,279 RAD 001C 05/19/2006 PHH020061T07069 Follow Up
`
`195
`
`194
`
`193
`
`66,279 RAD 001C 05/19/2006 FDA LETTER responding to the April 3, 2006, serial number
`182, request for SPA.
`
`66,279 RAD 001C 05/18/2006 Referencing General Correspondence Letter of
`Authorization SN 158. Novartis is amending the letter for the
`purpose of reflecting changes in the protocol title.
`
`Response to FDA Request
`
`Change In Protocol
`
`Safety Report
`
`Safety Report
`
`Other
`
`General Correspondence
`
`66,279 RAD 001C 05118/2006 Email to FDA following receipt of their responses, accepting
`the option of canceling the scheduled face-to-face meeting.
`
`Request for FDA Meeting
`
`66,279 RAD 001C 05/17/2006 Email from FDA with their responses to Novartis' questions
`for the EOP 1-2 meeting.
`
`Other
`
`66,279 RAD 001C 05/11/2006 PHH020061T07069 Follow Up
`
`66,279 RAD 001C 05/01/2006 Amendment No. 1 to Protocol 2222.
`
`191
`
`190
`
`Safety Report
`
`Change In Protocol
`
`66,279 RAD 001C 04/21/2006 Email response to FDA request for a summary document .
`outlining the requested information for the pivotal and
`supportive trials to be submitted for approval of RAD001.
`
`66,279 RAD 001C 04/13/2006 Amendment to Letter of Authorization, dated November 22, 188
`2005 (SN 153) in support of an IND that will be filed by
`Gerber Wulf, MD, PhD.
`
`66,279 RAD 001 C 04/13/2006 Study 2235 update to new investigator address
`
`66,279 RAD 001C 04/12/2006 Submitted 14 desk copies ofthe briefing book and
`appendices in anticipation of a possible meeting on May 20
`or June 12, 2006 to discuss the development plan and
`registration strategy for RAD001 (everollmus) in advanced
`metastatic renal cancer.
`
`66,279 RAD 001C 04/10/2006 PHH02005FR20026
`
`66,279 RAD 001C 04/07/2006 Request for Type B meeting to discuss the development
`plan and registration strategy for RAD001 in advanced
`metastatic renal cancer.
`
`189
`
`187
`
`186
`
`.185
`
`Response to FDA Request
`
`General Correspondence
`
`New Investigator
`
`Request for FDA Meeting
`
`Safety Report
`
`Request for FDA Meeting
`
`66,279 RAD 001C 04/07/2006 Email to FDA responding to request for a word document
`with the list of questions submitted in the briefing book for
`the SPA for protocol CRAD001 C2239.
`
`Other
`
`66,279 RAD 001C 04/05/2006 PHH02005US06739
`
`184
`
`Safety Report
`
`66,279 RAD 001C 04/04/2006 Email to FDA responding to their request for desk copies of
`the SPA as well as the indication.
`
`Response to FDA Request
`
`66,279 RAD 001 C 04/03/2006 Request for Special Protocol Assessmenrfor
`CRAD001 C2239.
`
`183 2239
`
`Other
`
`66,279 RAD 001 C 03/15/2006 PHNR2006AU00570
`
`66,279 RAD 001C 03/15/2006 PHNR2006AU00570 Follow Up
`
`66,279 RAD 001C 03/1412006 PHH02005US19658
`
`182
`
`181
`
`Safety Report
`
`Safety Report
`
`Safety Report
`
`
`
`

`
`REF PRODUC DATE
`
`DESCRIPTION
`
`SERI PROTOCOL SUBMISSION TYPE
`
`66,279 RAD 001C 03/14/2006 PHH02005US19658 Follow Up
`
`66,279 RAD 001C 0310812006 PHH02006CA03486
`
`180
`
`66,279 RAD 001C 0310812006 PHH02006CA03486 Follow Up
`
`66,279 RAD 001C 0212712006 This submission addresses FDA concerns regarding a
`number of adverse events associated with a clinical study of
`RAD001C in patients with renal cancer, which were
`submitted by Dr. Amato under private IND 71,586.
`
`179
`
`Safety Report
`
`Safety Report
`
`Safety Report
`
`General Correspondence
`
`66,279 RAD 001C 0212412006 This Annual Report covers the period December 25, 2004
`throughNovember 25, 2005. Includes clinical study·
`lnfonnation, abstract of published papers on RAD001
`(Oncology) and Appendix 1.
`
`178
`
`Annual Report
`
`66,279 RAD 001C 0212312006 Dr. George Demetri: Malignant neoplasm progression,
`ascites, cholelithlasis, pleural effusion, dyspnoea;
`Follow-up#1.
`
`177 2206
`
`Safety Report
`
`66,279 RAD 001C 02106/2006
`
`I FRANCE] Dr. Jean-Charles Soria: Mental disorder, back 176 2235
`pain, delusional disorder, persecutory type, myalgia;
`Follow-up#2.
`
`Safety Report .
`
`66,279 RAD 001C 02101/2006
`
`I FRANCE l Dr. Jacques Dental: Respiratory tract
`infection, lung disorder, fluid overload: Follow-up#1.
`
`175 2420
`
`Safety Report
`
`66,279 RAD 001C 01/24/2006
`
`[FRANCE] Dr. Jacques Dantal: Lung disorder.
`
`174 2420
`
`Safety Report
`
`66,279 RAD 001C 0111812006 The current submission provides response to questions
`raised by FDA and includes detailed data from protocol
`2206, which were identified as critical to resolve the clinical
`hold deficiencies for Dr. Ryan's IND 73,986.
`
`173 2206
`
`Response to Clinical Hold
`
`66,279 RAD 001C 0111812006
`
`[FRANCE] Dr. Jean-Charles Soria: Back pain, mental
`disorder, delusional disorder, persecutory type, myalgia;
`Follow-up#1.
`
`172 2235
`
`Safety Report
`
`66,279 RAD 001C 01/1812006 This submission provides response to questions raised by
`FDA and includes detailed data from protocol 2206, which
`were identified as critical to resolve the clinical hold
`deficiencies for Dr. Ryan's IND 73,986.
`
`66,279 RAD 001C 01111/2006 Dr. Howard Sher: Muscular weakness, myopathy steroid,
`hydrocephalus, cognitive deterioration, general physical
`health deterioration, mood altered, depression,
`cardiovascular disorder, fall; Follow-up#2.
`
`173
`
`Response to Clinical Hold
`
`171
`
`2408
`
`Safety Report
`
`66,279 RAD 001C 01/10/2006 E-MAIL from FDA containing response to NVS questions for
`discussion durtng January 12, 2006 meeting.
`
`Other
`
`66,279 RAD 001C 01/0312006
`
`[ BELGIUM I Dr. Van Oosterom: Gastritis haemorrhagic,
`right ventricular failure, pulmonary hypertension, anaemia,
`haematochezia, general physical health deterioration;
`Follow-up#1.
`
`170
`
`2206
`
`Safety Report
`
`66,279 RAD 001C 12130/2005
`
`[FRANCE] Dr. Jean-Charles Soria: Back pain, mental
`disorder, delusional disorder, persecutory type, myalgia.
`
`169
`
`C2235
`
`Safety Report
`
`66,279 RAD 001C 1212312005 Michelle Roos: Hyponatraemia, vomiting, diarrhoea, viral
`infection, dehydration.
`
`168
`
`AUS15
`
`Safety Report
`
`66,279 RAD 001C 1212212005 Dr. Howard Sher: Muscular weakness, myopathy steroid,
`hydrocephalus, fall; Follow-up#1.
`
`167
`
`2408
`
`Safety Report
`
`
`
`

`
`REF PRODUC DATE
`
`DESCRIPTION
`
`66,279 RAD 001C 12121/2005 NVS acknowledges receipt of FDA response dated July 7.
`2005 to Special Protocol Assessment requested for
`CRAD001 C2223, which was submitted to FDA on May 11,
`2005, and hereby requests additional information on
`statistical procedures outlined in the protocol.
`
`SERI PROTOCOL SUBMISSION TYPE
`
`166
`
`General Correspondence
`
`66,279 RAD 001C 12120/2005 Dr. Alex Adjei: Pulmonary embolism, malignant neoplasm 165 US15
`progression, chest pain, dyspnoea, respiratory failure,
`productive cough; Follow-up#2.
`
`Safety Report
`
`66,279 RAD 001C 12119/2005 Dr. Howard Sher: Muscular weakness, fall.
`
`163 2408
`
`Safety Report
`
`66,279 RAD 001 C 12119/2005 This submission provides the Edition 4 of the Investigators' 164
`Brochure, which replaces Edition 3, dated 30-Aug-2004.
`Also included is the summary of changes, outlining the
`updates incorporated in Edition 4.
`
`66,279 RAD 001C 12116/2005 Novartis is amending the Letter of Authorization submitted 162
`to the Agency on November 22, 2005, SN 151, in support of
`an IND that will be filed by Charles A. Coltman, Jr., MD.
`
`66,279 RAD 001C 12106/2005 This submission provides the briefing book and appendices, 161
`including cited references, for the January 12, 2006 meeting
`to discuss the development plan and registration strategy
`for RAD001 in carcinoid tumors and pancreatic
`neuroendocrine tumors. Three copies were forward to the
`Division of Oncology, as well as fourteen desk copies.
`
`Clinical Information Amendr
`
`General Correspondence
`
`General Correspondence
`Response to FDA Request
`
`66,279 RAD 001C 12106/2005 E-MAIL detailing questions presented in briefing document
`for the FDA meeting scheduled for January 12, 2006.
`
`Other
`
`66,279 RAD 001C 12/0212005 This letter authorizes FDA to refer to this IND in support of 160
`an IND that will be filed by Tiffany Svahn, MD.
`
`66,279 RAD 001C 12/0212005 This letter authorizes FDA to refer to this IND in support of 159
`IND that will be filed by Robert. J. Motzer, MD.
`
`66,279 RAD 001C 12/0212005 This letter authorizes FDA to refer to this IND in support of 158
`an IND that will be filed by Jonathan Rosenberg, MD.
`
`66,279 RAD 001C 1210212005 This letter authorizes FDA to refer to this IND in support of 157
`an IND that will be filed by Chandra Belani, MD.
`
`66,279 RAD 001C 1210212005 This letter authorizes FDA to refer to this IND in support of 156
`an IND that will be filed by Robert Figlin, MD.
`
`66,279 RAD 001C 1210212005 This letter authorizes FDA to refer to this IND in support of 155
`an IND that will be filed by John. D. Hainsworth, MD.
`
`General Correspondence
`
`General Correspondence
`
`General Correspondence
`
`General Correspondence
`
`General Correspondence
`
`General Correspondence
`
`66,279 RAD 001C 11/2212005 Richard Stone: Pneumonitis, nausea, dyspnoea, hypoxia,
`pleural effusion, performance status decreased, cough,
`pulmonary fibrosis, fatigue, productive cough, respiratory
`distress; Follow-up#4.
`
`154 2207
`
`Safety Report
`
`66,279 RAD 001C 1112212005 This letter authorizes FDA to refer to this IND in support of 153
`an IND that will be filed by Lyndsay N. Harris, MD.
`
`66,279 RAD 001 C 1112212005 This letter authorizes FDA to refer to this IND in support of
`an IND that will be filed by Shirish. M. Gadgeel, MD.
`
`151
`
`66,279 RAD 001C 1112212005 This letter authorizes FDA to refer to this IND in support of 150
`an IND that will be filed by Philip. J. Gold. MD.
`
`66,279 RAD 001C 11/2212005 This letter authorizes FDA to refer to this IND in support of 149
`~n IND that will be filed by John R. Murren. MD.
`
`66,279 RAD 001 C 1112212005 This letter authorizes FDA to refer to this IND in support of 148
`an IND that will be filed by Milind Javle. MD.
`
`General Correspondence
`
`General Correspondence
`
`General Correspondence
`
`General Correspondence
`
`General Correspondence
`
`
`
`

`
`REF PRODUC DATE
`
`DESCRIPTION
`
`SERI PROTOCOL SUBMISSION TYPE
`
`66,279 RAD 001C 11/2212005 This letter authorizes FDA to refer to this IND in support of 152
`an IND that will be filed by Mitchell Gross, MD.
`
`General Correspondence
`
`66,279 RAD 001C 11/17/2005
`
`(GERMANY] Prof. Struber: Renal impairment,
`immunosuppressant drug level increased, blood creatinine
`increased, drug interaction; Follow-up#1.
`
`146 DE06
`
`Safety Report
`
`66,279 RAD 001C 1111412005 Dr. Judith Wolf: Hyponatraemia, condition aggravated,
`anorexia, nausea, asthenla, muscle spasms, hypotension.
`
`145 2409
`
`Safety Report
`
`66,279 RAD 001C 11/11/2005 Dr. Lauren Abrey: International normalised ratio increased, 143 C2408
`haematuria, drug interaction; Follow-up#1.
`
`Safety Report
`
`66,279 RAD 001C 11/11/2005 This letter authorizes FDA to refer to this IND in support of 144
`an IND that will be filed by Christopher Ryan, MD.·
`
`General Correspondence
`
`66,279 RAD 001C 11/0112005 New Investigator to Study No. 2222: Dr. Stephen M.
`Schultz, MD.
`
`142 2222
`
`New Investigator
`
`66,279 RAD 001C 11/01/2005 Dr. Lauren Abrey: International normalised ratio Increased, 141 C2408
`haematuria.
`
`Safety Report
`
`66,279 RAD 001C 10/31/2005 This letter authorizes FDA to refer to this IND in support of 140
`an IND that will be filed by Francisco J. Esteve, MD.
`
`General Correspondence
`
`66,279 RAD 001C 10/31/2005 This letter authorizes FDA to refer to this IND in support of 139
`an IND that will bi filed by Lawrence S. Blaszkowsky, MD.
`
`Safety Report
`
`66,279 RAD 001C 10/31/2005 This letter authorizes FDA to refer to this IND in support of 138
`an IND that will be filed by Dr. Deborah Toppmeyer.
`
`66,279 RAD 001C 10/31/2005 This letter authorizes FDA to refer to this IND in support of 137
`an IND that will be filed by Amanda Psyni, MD.
`
`66,279 RAD 001C 10/31/2005 This letter authorizes FDA to refer to this IND in support of 136
`an IND that will be filed by Nooper Raje, MD.
`
`66,279 RAD 001C 10/31/2005 This letter authorizes FDA to refer to this IND in support of 135
`an IND that will be filed by Leonard B. Saltz, MD.
`
`66,279 RAD 001 C 10/3112005 This letter authorizes FDA to refer to this IND in support of 134
`an IND that will be filed by Manuel Hidalgo, MD., Ph.D.
`
`66,279 RAD 001 C 10/26/2005 E-MAILS to/from FDA requesting a meeting date. FDA
`scheduled a meeting for January 12, 2006 and requested
`the background package by December 8, 2005.
`
`66,279 RAD 001C 10/17/2005 This correspondence is a request for a Type B meeting with 133
`the Division of Oncology Drug Products to discuss the
`development plan and registration strategy for RAD001 in
`carcinoid tumors and pancreatic neuroendocrine tumors.
`
`General Correspondence
`
`General Correspondence
`
`General Correspondence
`
`General Correspondence
`
`General Corraspondfilllce
`
`Request for FDA Meeting
`
`Request for FDA Meeting
`
`66,279 RAD 001C 10/1412005
`
`( GERMANY ] Prof. Struber: Renal impairment, drug
`interaction, immunosuppressant drug level increased, blood
`creatinine Increased.
`
`132 ADE06
`
`Safety Report
`
`66,279 RAD 001 C 10/0412005 Dr. Alex Adjei: Pulmonary embolism, chest pain, dyspnoea, 131 AUS15
`respiratory failure, productive cough; Follow-up#1.
`
`Safety Report
`
`66,279 RA