otlertuzumab (TRU 016) / Emergent Biosolutions - LARVOL DELTA

Clinical Study on the Treatment of Immune Thrombotic Thrombocytopenic Purpura Using Protein a Immunoadsorption Therapy (ASH 2024) - "At present, TPE, glucocorticoids and rituximab are still used as first-line treatments in China where caplacizumab is unavailable...After 3 intermittent immunoadsorptions, 2 plasma exchanges, and 1 course of bortezomib (1.3mg/m2, d1,4,8,11) treatment, platelets increased to be normal on Day 19...On Day 4, otlertuzumab was given to clear the antibody (1000 mg, d1, 15), and then the third immunoadsorption treatment was performed on Day 8 for consolidation...It can reduce the amount of plasma used, avoid the risk of blood transfusion, and improve the rescue rate of iTTP patients. It is worthy of further exploration and research."

Clinical • Anemia • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Immunology • Infectious Disease • Novel Coronavirus Disease • Psychiatry • Renal Disease • Thrombocytopenia • Thrombocytopenic Purpura

Development of PSB202, a bifunctional antibody pair that target CD20 and CD37, for the treatment of B-cell malignancies (AACR 2022) - P1a/1b | "Systemic depletion of normal and malignant B-cells by anti-CD20 antibodies (e.g. rituximab and obinutuzumab) and anti-CD37 antibodies (e.g. otlertuzumab and BI 836826) has been well tolerated in clinical studies...Synergy was demonstrated for PSB202 in combination with lenalidomide...PSB202 offers the potential to improve clinical efficacy, decrease drug resistance, provide administration convenience especially when combining with additional therapeutics, lower the cost for treatment, and reduce the unwanted side effects from chemotherapy. PSB202 is currently being evaluated in patients with previously treated, relapsed, indolent B-cell malignancies (NCT05003141)."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Phase 1b Safety and Efficacy Study of TRU-016 (clinicaltrials.gov) - P1b; N=87; Terminated; Sponsor: Aptevo Therapeutics; Trial completion date: Dec 2020 ➔ Apr 2021; Active, not recruiting ➔ Terminated; Business decision

Clinical • Combination therapy • Trial completion date • Trial termination • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Emergent initiates phase 2 study of TRU-016 in combination with bendamustine in patients with relapsed chronic lymphocytic leukemia (Business Wire) - Emergent BioSolutions initiation of a phase 2 study of TRU-016 in combination with bendamustine for patients with relapsed CLL with a milestone payment of $6M

Initiation of P2 trial • Hematological Malignancies • Oncology

Phase 1b Safety and Efficacy Study of TRU-016 and Rituximab or Obinutuzumab in Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1; N=56; Active, not recruiting; Sponsor: Emergent Product Development Seattle LLC; N=24 -> 56

Enrollment change • Biosimilar • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology

Emergent Biosolutions: Credit Suisse Antibody Day (Emergent Biosolutions) - "Preliminary results"; "Different levels of Assessment"; "Best Response at any time per investigator"; "NCI: 2 months duration, PE and CBC"; "IWCLL: same as NCI but includes CT scan and for CR 2 months duration is after completing Rx"; "4 CRs under NCI did not reach IWCLL criteria"; "2 did not have repeat scans"; "2 had nodes >1.5 cm; 1.6 cm and other 1.8 cm"

P1/2 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma

Emergent BioSolutions' otlertuzumab (TRU-016) shows positive results in combination with rituximab in people with CLL (Emergentbiosolutions Press Release) - P1, N=56; Study 16009; “Emergent is pleased with the data from Cohort 1 of this Phase 1b study that show the safety and activity of otlertuzumab in combination with rituximab,...Otlertuzumab was well tolerated in Cohort 1. 54 percent of patients experienced infusion reactions, most of which were grade 1 or 2 with only two grade 3 reactions."

P1 data • Non-Hodgkin’s Lymphoma • Oncology

Emergent Biosolutions: Credit Suisse Antibody Day (Emergent Biosolutions) - Anticipated presentation of data from P1b/2 trial for relapsed chronic lymphocytic leukemia at ASH (Dec 07-10, 2013); Anticipated presentation of data from P1b trial for first-line chronic lymphocytic leukemia at ASH (Dec 07-10, 2013)

Anticipated P1 data • Anticipated P1/2 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma

Phase 2 study of otlertuzumab (TRU-016), an anti-CD37 ADAPTIRTM protein, in combination with bendamustine vs bendamustine alone in patients with relapsed chronic lymphocytic leukemia (CLL) (ASH 2013) - Presentation time: Sunday, December 8, 2013: 6:30 PM-8:30 PM; Abstract #2860; P2, N=65; Sponsor: Emergent Product Development Seattle LLC; NCT01188681; “The ORR for the combination of otlertuzumab and benda (n=20) was 80% (16) with a CR rate of 20% (4).  For benda alone (n=24) the ORR was 42% (10) with a CR rate of 4% (1).  Patients are still in treatment and follow-up but only 10% (2) have progressed on the combination of otlertuzumab and benda while 46% (11) have progressed on benda.  The best response at anytime by NCI criteria using available data for the combination of otlertuzumab and benda (n=32) was ORR 78% and CR 16% and for benda alone (n=33) ORR 52% and CR 9%.” 

P2 data • Non-Hodgkin’s Lymphoma • Oncology

Emergent Biosolutions: Credit Suisse Antibody Day (Emergent Biosolutions) - "Progression Free Survival Intent to Treat by Response"

P1 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma

Phase 1b safety and efficacy study of TRU-016 and rituximab in previously untreated chronic lymphocytic leukemia (clinicaltrials.gov) - P1, N=24; Not yet recruiting; New P1 trial

New P1 trial • Hematological Malignancies • Non-Hodgkin’s Lymphoma

Phase 1b study of otlertuzumab (TRU-016), an anti-CD37 ADAPTIRTM protein, in combination with rituximab in patients with previously untreated chronic lymphocytic leukemia (CLL) (ASH 2013) - Presentation time: Monday, December 9, 2013: 6:00 PM-8:00 PM; Abstract #4165; P1, N=24; NCT01644253; "Six patients have had CT scans and bone marrow assessments 3 months after their last dose of study drug; by IWCLL criteria 1 has a CR, 4 have a PR and 1 has SD."

P1 data • Non-Hodgkin’s Lymphoma • Oncology

Emergent Biosolutions: Q2 2013 Results (Emergent Biosolutions) - Anticipated presentation of data from P1b/2 (bendamustine combo) trial for relapsed chronic lymphocytic leukemia at ASH (Dec 07-10, 2013); Anticipated presentation of data from P1b (rituximab combo) trial of expanded cohort and original cohort for first-line chronic lymphocytic leukemia at ASH (Dec 07-10, 2013); Anticipated completion of enrollment of expanded cohort in P1b (rituximab combo) trial for first-line chronic lymphocytic leukemia by end of 2013

Anticipated enrollment status • Anticipated P1 data • Anticipated P1/2 data • Non-Hodgkin’s Lymphoma • Oncology

Emergent BioSolutions presents positive interim phase 2 data evaluating otlertuzumab (TRU-016) in combination with bendamustine in people with relapsed chronic lymphocytic leukemia (Emergentbiosolutions Press Release) -

P2, N=65; Study 16201; "Data show that otlertuzumab in combination with bendamustine produced a higher response rate than bendamustine alone by International Workshop on CLL (IWCLL) and National Cancer Institute (NCI) response criteria. Overall incidence of adverse events, severe and serious adverse events were generally similar in both arms of the study."

P2 data • Non-Hodgkin’s Lymphoma • Oncology

Phase 1b study of otlertuzumab (TRU-016), an anti-CD37 monospecific ADAPTIR therapeutic protein, in combination with rituximab and bendamustine in relapsed indolent lymphoma patients (Invest New Drugs) - P1, N=12; NCT01317901; "All patients had relapsed after prior rituximab including 7 refractory to their most recent previous treatment. In the 10 and 20 mg/kg dose cohorts, the mean half-life was 8 and 10 days following the first dose, and 12 or 14 days following 12 doses of otlertuzumab, respectively. Overall response rate was 83 % (10/12) with 4 CRs (32 %)."

P1 data • Non-Hodgkin’s Lymphoma • Oncology

Emergent BioSolutions: Annual Report 2012 (Emergent Biosolutions) - Anticipated patent expiries in January 17, 2022 & November 1, 2029

Anticipated patent expiry • Non-Hodgkin’s Lymphoma • Oncology

Emergent’s TRU-016 for CLL receives orphan medicinal product designation from European Commission (Business Wire) - "Emergent BioSolutions...announced that the European Commission granted orphan medicinal product designation to...TRU-016, for the treatment of chronic lymphocytic leukemia (CLL)...TRU-016 is currently being evaluated in a randomized Phase 2 study (16201) in combination with bendamustine compared to bendamustine alone in relapsed CLL patients. The primary outcome measurement for this study is overall response rate and data are expected in the second half of 2013."

Anticipated P2 data • Orphan drug • Non-Hodgkin’s Lymphoma • Oncology

Emergent BioSolutions announces acceptance of four TRU-016 abstracts for presentation at 2011 American Society of Hematology annual meeting (Business Wire) - Four abstracts on TRU-016 accepted for presentation at the 53rd Annual Meeting of the ASH which include the clinical results from a Phase 1 study evaluating patients with CLL and NHL & synergistic or additive effect of TRU-016 with multiple agents demonstrated in pre-clinical models

Data presentation • Oncology

Anti-CD37 antibodies for chronic lymphocytic leukemia (Expert Opin Biol Ther) - "The results of preclinical and early clinical studies suggest that in patients with CLL, newer anti-CD37 agents, otlertuzumab (formerly known as TRU-016), BI 836826, IMGN529 and 177Lu-tetulomab can be useful in the treatment of this disease."

Review • Non-Hodgkin’s Lymphoma • Oncology

Phase 1b Safety and Efficacy Study of TRU-016 (clinicaltrials.gov) - P1b; N=87; Active, not recruiting; Sponsor: Aptevo Therapeutics; Trial completion date: Dec 2019 ➔ Dec 2020; Trial primary completion date: Oct 2019 ➔ Oct 2020

Clinical • Combination therapy • Trial completion date • Trial primary completion date

NEW DRUGS FOR NON‐HODGKIN LYMPHOMA: BEYOND CHEMOTHERAPY: NEW DRUGS FOR OLD TARGETS (ICML 2019) - P1, P1/2, P1a/1b, P1b, P1b/2, P2, P2/3, P3; "...Ofatumumab was approved for patients with chronic lymphocytic leukemia (CLL) at different lines of treatment of this disease, alone or in combination, but failed to demonstrate a benefit and to gain approval in phase 3 studies performed in combination with chemotherapy in relapsed diffuse large B-cell lymphoma (DLBCL) (NCT01014208) or as single agent in patients with relapsed/refractory (R/R) follicular (FL) or other indolent lymphoma (NCT01200589)...In a randomized study comparing bendamustine single agent versus bendamustine combined with obinutuzumab and followed by obinutuzumab maintenance in patients who were assessed as refractory to rituximab, the experimental arm resulted in significant progression free survival (PFS) and overall survival (OS) benefits.6 The GALLLIUM phase 3 study7 demonstrated a significant improvement of PFS in combination with chemotherapy in untreated patients with FL, while no benefit was observed in the

Phase 1b Safety and Efficacy Study of TRU-016 (clinicaltrials.gov) - P1b; N=123; Active, not recruiting; Sponsor: Aptevo Therapeutics; Trial primary completion date: Jun 2019 ➔ Oct 2019

Clinical • Combination therapy • Trial primary completion date

Aptevo Therapeutics reports third quarter 2018 financial results (GlobeNewswire) - "Commenced site activation for the APVO436 Phase 1/1b open-label clinical study; anticipate patient dosing to commence shortly.......we have made the decision to focus our resources on our next-generation candidates, which we consider to be the most promising opportunities in our pipeline, and discontinue further development of our first-generation ADAPTIR candidates, otlertuzumab and APVO414. Going forward we will close the otlertuzumab and APVO414 clinical studies to further enrollment but will continue to monitor patients remaining on therapy."

Enrollment status • Trial status