CENTRAL ETHICS COMMITTEE We Thriv or Buality

To, Date: 15'h April 2011 Dr. Nita Raizada Narang Chinmaya Mission Hospital, CMH Road, Indira nagar, Banglore-560038

Subject: Ethics Committee approval for the conduct of the referenced study.

Reference: Study Code: B1931008 Study Title: An open - label, randomized, phases study of Inotuzumab Ozogamicin administered in combination with Rituximab compared to defined investigators choice therapy in subjects with relapsed or refactory CD 22 positive, aggressive, Non Hodgkin Lymphoma who are not candidates for intensive high -dose chemotherapy

Dear Dr. Niti.Raizada Narang, We have received from you the following documents:

1. Protocol version 5 Nov 2010 2. Informed Consent Form version 26 Nov 2010 in English and translations in Hinds, Kannada and Telugu languages 3. Exposure in Utero form version dated 29 Nov 2010 in English 4. Enclosed are the following Subject Administered Questionnaires in English with translations in Hindi, Kannada and Telugu languages. - FACT-Lym and - EQ-5D 5. Investigator's Brochure dated Oct 2009 and Safety Attachments dated 27 h Oct 2009 and 17d Sep 2010. 6. Safety letters as specified below

iyderabnd Central Ethics Committee # 12-13-392, Street W 1, Leas No. 4, Tamaka, Hyderabad-500017, Andhra Pradesh, . Phone: +6' .40-2700,0307,+9140-27000305, Teletax : 040-27000259 E-mail; "rabadoeoftmail.tom HYDERABAD CENTRAL ETHICS COMMITTEE

SIR Date SAE Report SAE event Type of Report Number I¢itiaUFoOow-

17-Aug-2010 GB-WYE- TUMOURLYSISSYNDROMWLLT:TUMOURLYSIS Initial 1416795010 SYNDROME) LLT = Lowest Level Tenn 14-Sep-2010 GB-WYE- TUMOUR LYSIS SYNDROME(LLT:TUMOUR LYSIS Follow ¢p H16795010 SYNDROME) LLT= Lowest Level Temp 13-Sep-2010 - HU-WYE- PNEUMONIA(LLT:PNEUMONIA);Fatigue(LLT:Fatigpe) Initial H16895210 [LLT = Lowest. Level Tenn]

15-Sep-2010 HU-WYE- PNEUMONIA(LLT:PNEUMONIA);.Fatigue(LLT:Fatigue) Follow up H16895210 [LLT=Lowest Level Term]

27-Sep-2010 HU-WYE- PNEUMONIA(LLT:PNEUMONIA); Fatigue(LLT:Fatigue) . Follow up H16895210 [LLT=Lowest Level Tenn]

28-Jul-2010 JP-WY& PYREXIA(LLT:FEVER) Initial HIS980610 [LLT=Lowest level Term]

28-Sep-2010 JP-WYE, HERPES ZOSTER(LLT:HERPES ZOSTER) Initial 1117731610 [LLT= Lowest Level Term]

22-Jul-2010 KR-WYE- HEPATITIS B(LLT;VIRAL HEPATITIS B) initial H16083210 [LLT - Lowest Level Tam]

14-Sep-2010 KR WYE- HEPATITIS B(LLT;VIRAL HEPATITIS B) Follow up H16083210 [LLT = Lowest Level Term)

22-Sgr2010 -WYE- HEPATITIS B(LLT:VIRAL HEPATITIS B) Follow up H16083210 [LLT - Lowest Level Term]

04-1un-2010 SO-WYE- 'IH1tOMBOCYTOPEMA(LLT:THROMHOCYTOPENIA) Initial H15444010 [LLT = Lowest Level Term)

064W-2010 SG-WYE THRb BOCYTpPENIA(LGT THROMEOCY IOPENIA) H15444010 [LLT = Lowest Level Term] Follow up

07-1111-2010 SG-WYE- THROMSOGYTOPENIA(GLT:THROMBOCYTOPENiA) Initial H15926710 [LLT—Lowest Level'Terml

13- SG-WYE- THROMBOCY"TOPENIA(LLT:THROMBOCYTOPENIA) initial Jul-2010 HIS981410 [LLT - Lowest Level Term]

Ayderadad Central Ethics Committee II 12-13.392, Street N :. t, Lane No. 4, Temake, Hyderabad-500017, Andhra Pradesh, India Phone : +9 1-40-27000307, +91 .40.27000306, TeWax : 040-27000259 E-mail: hyderab" ll.com

^l^ HYDERABAD IM' CENTRAL ETHICS COMMITTEE 1>'^e TltriY or QIla11tV

30-Jut-2010 SG-WYE- THROMBOCYTOPENIA(1.LT:THROMBOCYTOPENIA) Follow up H15981410 [LLT = Lowest Level Term]

28-Jul-2010 SG-WYE- THROMBOCYTOP A(LLT:THROMBOCYTOPENIA) Initial H16408710 [LLT - Lowest Level Term]

30-Jul-2010 SO-WY& THROMBOCYTOPENIA(I LT:THROMBOCYTOPENIA) Follow up H16409710 [LLT = Lowest Level Term]

04-Aug-2010 SG-WYE- ANAEMIA(LLT:ANEMIA);Neutropenic Initial H16528710 sepsis(LLT:Neutropcnicsepsis) [LLT = Lowest Level Term] 20-Sep-2010 SO-WYE- ANAEMIA(LLT:ANEMIA); Adrenal Follow up H16528710 insuffrciency(LLT:Corticoadrenal insufficiency); Neutropenic sepsis(LLT:Neutropenic sepsis) LT = Lowest Level Term 08-Sep-2010 US-WYE- NODULAR REGENERATIVE Follow up 1108917709 HYPERPLASIA(LLT:NODULARREGENERATIVE HYPERPLASIA) LT — Lowest Level. Term 09-SW2010 US-WYE- NODULAR REGENERATIVE Follow up H12818910 HYPERPLASIA(LLT:NODULARREGENERATIVE HYPERPLASIA) LLT =Lowest Lave! Term 30-,-W2010 US-WYE- BILIARY CIRRHOSIS(LLT:BILIARY CIRRHOSIS); 1117593310 Ascites(LLT:Ascitesr Oedema Initial peripheral(LLT:Edwa oflower extremities); Portal hypWtMsi%1a1T:Pate1 hypertension). LT = Lowest Level TO MIrm 2010 KRR-WYE- HEPATITIS T:VIRAL HEPATITIS B) Follow up H160MIO [LLT = Lowest Level Tam]

14-Oct-2010 SCf-WYE- NEUTROPENIC EPSIS(LLT:NEUTROPENICSEPSIS) InW H17979510 [LLT = Lowest Level Term]

27-Oct4010 US-WYE- Bit dARY CIRRHC)St9(LLTMLIARY CIRRHOSIS); Follow up H17593310 Aseites(LLT:Ascitea); Oedema peripheral(LLT:Edetna of lower extren hies); Portal hyptrrenaion(LLT:Poml hypertension) [LLT - Lowest Level Term]

28-0ct-2010 US- VENOOCCLUSIVE LIVER Initial HIS297610 DISEASE(LLT:VENOOCCLUSFVELTVERDISEASE) [LLT = Lowe" Level Tam]

#yderabad Central Ethics Committee # 12-13-392, Street N t. 1, Lane No. 4, Tamaka, Hydembad-500017, Andhra Pradesh, India. Phone: +9 -40-27000307, +91 .40-27000306, Telefax : 040-27000259 E-mail i hyderabadoec(Urnsil.com ^ r HYDERABAD ^ r CENTRAL ETHICS COMMITTEE We Thriv or orranty

29-Oct-2010 US-WYE-1118303110 BACTERIAL SEPSIS(LLT:SEPTICAEMIA Ini..al GRAM-POSITIVE) LT — Lowest Level Term 30-NOV-2010 2010154509 Febrile neutropenia [Febrile Initial neutropenial

30-NOV-2010 2010153843 Neutropeniesepals initial [Neutropenic sepals]

7. Case Report Form version 21 Oct 2010. 8. Patient ID Card for use to be given to the patients In the study, patients will be given ID cards at the time of baseline visit after randomization (enclosed for your reference). This ID card has information such as patient's nameiconted details,, identification as a study participant and serves as a reference to any other physicianfconsultam for them to know and contact the site and principal investigator. Besides these, them is no other study related information on this ID card. As per ICH-GCP guideline 8.2.7 any document given to the patient may require EC approval. In view of this, please find enclosed the patient ID card for your review & please grant the approval for the use of the same. 9. In the study we will be using the following proposed method of patient accrual: - Patiettis visiting our hospitainnstitute OPD's - Referred patients from primary health care cenoWpAvate practitioners or other Irutivacs/ Hospitals through verbal communication and discussion - Patient Database 10.Insurance Certificate/Compensation for serious adverw events occurring during the study participation [as per agreement with sponsor (draft tempfaW)and Informed Consent Document) 11.Principal Investigator's current CV. 12.Investigator's Undertaking (As required by Appendix. VII as per Schedule Y 20 Ian 2005 amendment) 13.Investigator's agreement with sponsor (draft template). 14.We plan to enroll 10 subjects in this study, This is for your notification 15, Patient travel and other expense reimbursement at the rue ofIllolfor patients within the city aud45jWWor patients outside the city. 16. We will be using the below mentioned labs for this study.

I lyderabod Central Ethics Committee # 12-1a-392, Street Nc 1, Lane No. 4, Tamaka, Hyderabad -600t117, Andhra Pradesh, India. Phone: +91 :4027000807, +91-4047000305, Telerfax : 040-27000259 E-mail: hyderabadeec®gntail.corn HYDERABAD ow CENTRAL ETHICS COMMITTEE we Thriv or Quality

Central,aba: Esoteric: Clinical Trials Services 1912 Almumder Drive Research Triangle Park (RTP) North Carolina 27709 USA

Alta Analytical Laboratory 3985 Sorrento Valley Blvd, Suite C San Diego, CA 92121 USA

Clearstone Central Laboratories Blk 33 #03-06 Marsiling Industrial Estate Road 3, Woodlands Central Industrial Estate Singapore 739256

Biomedical Systems 77 Progress Parkway St Louis, Missouri 63043 USA

Local Lab:

Elbit Medical Dlaguostics Limited, Indian Express Building, 1 &IA Queens Road, Bangalorea560001, . India

At the Hyderabad Central Ethics Committee meeting held on a Apr 2011, Time: 06:00 PM to 9:00 PM at Consulate Room, Hotel Nakshatra, Secanderabad-500001, and the above mentioned document; were examined, reviewed and discussed.

Hy. lerabad Centmi EthMcs Committee # 12-13.992, $"at No_ 1, lane No. 4, TamaM, Hyderabad-500017, Andhra Pradesh, India. Phone : +91-4( (7000307, +91-40.27000905, Teletex : 040-27000259 E-mail: hydarebedceefgmaU.txxn

^ S HYDERABAD

We r Quality CENTRAL ETHICS COMMITTEE

The members who attended the meeting at which your study proposal was discussed are as follows: SNo NameoftheMember Rohe in the EC Qualifteation I. Mr.A. Venkat Rao Chair Person Retired IPS officer 2. Dr. San4eev Sharma Medical Scientist M.D (Clinical Pharmacologist) 3. Dr. Ashish Tukaram Patil Clinician M.B.B.S, RC.C.M 4. Mr. S. Durga Prasad Legal Person L.L.B (Advocate) 5. Mr.S.Krishnamurthy Lay Person B.Com 6. Mr. P, Satish Babu Social Activist Social Activist 7. Ms. Adimula Madhuri Member Secretary M.Sc. Clinical Research

We approve the trial to be conducted in its presented form, The approval is valid for a year from the date of approval. The approval is valid only after the regulatory approval from the Drugs Controller General of India has been obtained. We hereby confirm that neither you nor any of your study team members have participated in the voting/ decision waking procedure of the committee. The members of the committee who have participated in the voting/ decision making procedure of the committee do not have any conflict of interest in the referenced study.

The proposed method of patient recruitment is from Hospital database. if PI intends to use methods other than the above, He Rill do the same only after he receive our favourable o pinion for the same. The Hyderabad Central Ethics Committee expects to be informed about: 1. The progress of the study half yearly. 2. Any SAE occurring in the course of the study. 3. Any changes in the protocol and patient informatior linfornted consent Also you are requested to provide a copy of the final report. This Ethics Committee is organized and operates according to flood Clinical Practice and Schedule Y requirements.

Yours sincerely, e 1 qo 2011 Ma. Adimula Madburi wow camp' Ia, 0 5 SEP Member Secretary, ! t2.13 5112. Strreat NoA Larw 4n, Hyderabad Central Ethics CommitttAlr, q,EC4,ji" l D-00% f if . RECEIVED 0N

Hydl iabad Central Ethics COMMittes # 12-13-392, Street No. 1, L ie No. 4, Tamale, Hyderabad-500017, Andhra Pradesh, India. Phone: +91-0-2'000307, .91-40.271100305, Telefax : 040-27000259 is-mail : hyderabadceeftmall.com