Preliminary Results from NexImmune’s Phase 1/2 Trial of NEXI-001 in AML Presented at 62nd ASH Annual Meeting and Exposition – GlobeNewswire

December 07, 2020 17:31 ET | Source: NexImmune, Inc.

GAITHERSBURG, Md., Dec. 07, 2020 (GLOBE NEWSWIRE) -- NexImmune, a clinical-stage biotechnology company developing a novel approach to immunotherapy designed to employ the bodys own T cells to generate a specific, potent and durable immune response that mimics natural biology, today announced that City of Hopes Monzr Al Malki, M.D., delivered an oral presentation at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition featuring initial data from the Phase 1/2 trial of NEXI-001 in AML. Entitled Preliminary Results of the First-in-Human Study of NEXI-001, a Multi-Antigen Specific CD8+ T Cell Product, in Acute Myeloid Leukemia (AML) Patients with Relapsed Disease after Allogeneic Hematopoietic Cell Transplantation (Allo-HSCT) Demonstrate Early Signs of Safety, Tolerability and Robust Immune Responses, the presentation included responses following a single infusion of the experimental therapy.

These data represent safety and tolerability results from the first five patients treated and reflect a median of four months of follow-up with infusion doses ranging from 50-200 million total T cells. As noted by Dr. Al Malki in his presentation, there have been no cases of acute Graft versus Host Disease (aGvHD), Cytokine Release Syndrome (CRS), immune cells-associated neurological syndromes (ICANs), or infusion related reactions (IRRs) reported to-date, nor have there been any treatment-related adverse events (AEs) observed.

Biomarker data characterizing initial immunologic responses for the first three patients analyzed were also shared. Absolute lymphocyte counts, or ALC, were followed over time after the administration of lymphodepleting therapy, and showed a rapid return to baseline levels for each patient assessed (range 3 to 35 days). In addition, data on T cell reconstitution after lymphodepletion demonstrated that a single infusion of NEXI-001 T cells triggered a broad, rapid and robust immune response, inclusive of both CD8+ and CD4+ T cell types. TCR analysis showed the presence, persistence, expansion and migration of individual NEXI-001 T cell clones from the peripheral blood to the bone marrow of each patient. Finally, the immune phenotype of individual T cell subtypes in each NEXI-001 product were maintained in the peripheral blood of each patient at all time points measured, up to two months. These included sustained populations of T stem-cell-like memory and T central memory subtypes.

Early results from this Phase 1/2 trial suggest that infusion of the NEXI-001 product is well-tolerated and capable of triggering early, robust and persistent cell-mediated immune responses, said Dr. Al Malki, the trials lead investigator and associate clinical professor in City of Hopes Department of Hematology & Hematopoietic Cell Transplantation. The initial data are encouraging, and we look forward to dosing more patients with longer follow-up in order to more fully characterize the clinical potential of this exciting new cell therapy.

Relapse after allo-HSCT is the leading cause of death in patients with AML and represents a significant challenge for treating physicians. There are no approved therapies, and current treatment options are limited. Donor lymphocyte infusions (DLIs) represent the current standard of care but are associated with modest Graft versus Leukemia (GvL) responses and high rates of life-threatening GvHD-associated toxicities. There is significant need for new cellular therapies with potential to enhance the benefits of GvL while decreasing the incidence of GvHD-related toxicities.

Han Myint, M.D., Chief Medical Officer at NexImmune, added, While still early in this trial, we believe the initial data reported, combined with the unique and consistent composition of each NEXI-001 product, may offer a cell therapy with potential to decouple the benefits of GvL from the toxicities associated with GvHD, which would be transformative for both allogeneic stem cell transplant patients and the physicians that provide care for them.

About the Phase 1/2 NEXI-001 Clinical Trial The first clinical trial with NEXI-001 is a prospective, multi-center, open-label, single-arm, dose-escalating Phase 1/2 study that aims to enroll between 22 to 28 patients. The primary objective is to assess the safety and tolerability of a single infusion of NEXI-001 T cells in patients with AML who have either minimum residual disease (MRD) or relapsed disease after a human leukocyte antigen (HLA)-matched allo-HSCT. Secondary objectives include signals of immunologic responses and preliminary anti-tumor activity. Additional analysis will assess the in vivo persistence, proliferation, functionality and TCR repertoire of NEXI-001 T cells as measured in blood and bone marrow samples.

This study includes two phases. The initial Safety Evaluation Phase determines the safety and tolerability of a single infusion of NEXI-001 at escalating dose levels. In the second part of the study, the Dose Expansion Phase, investigators further define safety and will also evaluate the initial efficacy of NEXI-001 T cells at the dose established in the Safety Evaluation Phase. Once a Recommended Phase II Dose has been determined, safety, tolerability and initial clinical response will become the objectives of the expansion phase of the trial, which is expected to begin in [the first quarter] of 2021.

NEXI-001 products contain populations of CD8+ T cells directed against HLA 02.01-restricted peptides from the WT1, PRAME and Cyclin A1 antigens, each of which is commonly over-expressed on AML blasts and leukemic stem cells. Each NEXI-001 product is composed of T cell memory subtypes that combine anti-tumor potency with long-term persistence. Of significance to this Phase 1/2 trial, each patient-specific experimental cell therapy product also contains very low proportions of T cell subtypes with potential to cause GvHD-related toxicities.

About NexImmune NexImmune is a clinical-stage biotechnology company developing unique approaches to T cell immunotherapies based on its proprietary Artificial Immune Modulation (AIM) technology. The AIM technology is designed to generate a targeted T cell-mediated immune response and is initially being developed as a cell therapy for the treatment of hematologic malignancies. AIM nanoparticles act as synthetic dendritic cells to deliver immune-specific signals to targeted T cells and can direct the activation or suppression of cell-mediated immunity. In cancer, AIM-expanded T cells have demonstrated best-in-class anti-tumor properties as characterized by in vitro analysis, including a unique combination of anti-tumor potency, antigen target-specific killing, and long-term T cell persistence. The modular design of the AIM platform enables rapid expansion across multiple therapeutic areas, with both cell therapy and injectable products.

NexImmunes two lead T cell therapy programs, NEXI-001 and NEXI-002, are in Phase 1/2 clinical trials for the treatment of relapsed AML after allo-HSCT and multiple myeloma refractory to at least three prior lines of therapy, respectively. The Companys pipeline also has additional preclinical programs, including cell therapy and injectable product candidates for the treatment of solid tumors, autoimmune disorders and infectious diseases.

For more information, visit http://www.neximmune.com.

Media Contact: Mike Beyer Sam Brown Inc. Healthcare Communications 312-961-2502 mikebeyer@sambrown.com

Investor Contact: Chad Rubin Solebury Trout +1-646-378-2947 crubin@soleburytrout.com

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Preliminary Results from NexImmune's Phase 1/2 Trial of NEXI-001 in AML Presented at 62nd ASH Annual Meeting and Exposition - GlobeNewswire

BeiGene Announces the Approval in China of BLINCYTO (Blinatumomab) for Injection for Adult Patients with Relapsed or Refractory B-Cell Precursor Acute…

BEIJING & CAMBRIDGE, Mass.--(BUSINESS WIRE)--BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biotechnology company focused on developing and commercializing innovative medicines worldwide, today announced that the China National Medical Products Administration (NMPA) has approved BLINCYTO (blinatumomab) for injection for the treatment of adult patients with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL). The biologics license application (BLA) had been submitted by Amgen and received priority review by the Center for Drug Evaluation (CDE) of the NMPA. Developed by Amgen and licensed to BeiGene in China under a strategic collaboration commenced earlier this year, this is the first approval for BLINCYTO in China and BeiGenes first product licensed from Amgen to be newly approved. With this approval, BLINCYTO has become the first bispecific immunotherapy approved in China.

This approval of BLINCYTO provides us with an opportunity to offer adult patients in China with relapsed or refractory B-cell precursor ALL the first approved immunotherapy treatment for their disease. BLINCYTO is the first immunotherapy to demonstrate superior overall survival versus chemotherapy, more than doubling patients chances for survival, when used in first salvage R/R ALL in studies outside of China, commented Xiaobin Wu, Ph.D., General Manager of China and President of BeiGene. We are working to ensure BLINCYTO is available to patients in China as soon as possible. Our commercial organization of more than 1,500 people in China is excited to add BLINCYTO to our product portfolio, which now includes six approved cancer treatments.

The approval of BLINCYTO was based on results from the Phase 3 trial (NCT03476239) in China evaluating the efficacy and safety of BLINCYTO in adult patients with Philadelphia-negative R/R B-cell precursor ALL. Results of the interim analysis of 67 patients showed that the efficacy results in Chinese subjects were generally consistent with those in the global and Japan studies in subjects with Philadelphia-negative R/R ALL. The complete response/complete response with partial recovery of blood cells (CR/CRh) rate within two cycles of BLINCYTO treatment (the primary endpoint) was 47.8% (32 of 67 subjects; 95% CI: 35.4, 60.3). The median overall survival time was 9.6 months (95% CI: 6.4, not estimable). The safety profile observed for Chinese subjects in this study was consistent with that observed in the global studies evaluating BLINCYTO in R/R ALL. No new safety risks were identified based on these interim analyses of adverse events in Chinese subjects.

Our collaboration with BeiGene is advancing Amgens oncology pipeline for patients with significant unmet medical needs. We are confident the approval of BLINCYTO in China has the potential to make a meaningful difference to adult patients with R/R B-cell precursor acute lymphoblastic leukemia, said My Linh Kha, Vice President & General Manager, Amgen Japan Asia-Pacific (JAPAC). We are deeply committed to continuing to bring therapeutic options to treat debilitating cancers for patients in China, while also actively supporting the Governments focus on healthy aging through innovative products and initiatives designed to prevent chronic diseases, such as cardiovascular disease and fragility fracture.

About Acute Lymphoblastic Leukemia (ALL)

Acute lymphoblastic leukemia (ALL), also known as acute lymphocytic leukemia, is a rapidly progressing cancer of the blood and bone marrow that occurs in both adults and children1. ALL accounts for approximately 20% of all adult leukemia, and in China there were an estimated 82,607 new cases of leukemia in 20182,3. In children, the relapse rate of ALL is nearly 10%, while in adults the relapse rate is closer to 50%4.

About BLINCYTO (blinatumomab)

BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE) immuno-oncology molecule that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

BiTE molecules are a type of immuno-oncology therapy being investigated for fighting cancer by helping the body's immune system to detect and target malignant cells. The modified molecules are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE immuno-oncology molecules help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE immuno-oncology therapies are currently being investigated for their potential to treat a wide variety of cancers.

BLINCYTO was granted breakthrough therapy and priority review designations by the U.S. Food and Drug Administration and is approved in the U.S. for the treatment of:

In the European Union (EU), BLINCYTO is indicated as monotherapy for the treatment of:

In China, BLINCYTO is indicated for the treatment of adult patients with relapsed or refractory B-cell precursor ALL.

Important U.S. Safety Information

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

Contraindications

BLINCYTO is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions

Adverse Reactions

Dosage and Administration Guidelines

Please see full Prescribing Information and medication guide for BLINCYTO at http://www.BLINCYTO.com.

About BeiGene

BeiGene is a global, commercial-stage biotechnology company focused on discovering, developing, manufacturing, and commercializing innovative medicines to improve treatment outcomes and access for patients worldwide. Our 4,700+ employees in China, the United States, Australia, Europe, and elsewhere are committed to expediting the development of a diverse pipeline of novel therapeutics. We currently market two internally discovered oncology products: BTK inhibitor BRUKINSA (zanubrutinib) in the United States and China, and anti-PD-1 antibody tislelizumab in China. We also market or plan to market in China additional oncology products licensed from Amgen Inc., Celgene Logistics Srl, a Bristol Myers Squibb (BMS) company, and EUSA Pharma. To learn more about BeiGene, please visit http://www.beigene.com and follow us on Twitter at @BeiGeneUSA.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the commercialization and potential benefits of BLINCYTO; and BeiGenes plans and expectations for the commercialization of its and Amgens other oncology products and pipeline assets. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; BeiGene's ability to achieve commercial success for its marketed products and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its technology and drugs; BeiGene's reliance on third parties to conduct drug development, manufacturing and other services; BeiGenes limited operating history and BeiGene's ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates; the impact of the COVID-19 pandemic on the Companys clinical development, commercial and other operations, as well as those risks more fully discussed in the section entitled Risk Factors in BeiGenes most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law.

BLINCYTO and BiTE are registered trademarks of Amgen Inc.

1 Mayo Clinic. Acute lymphocytic leukemia. https://www.mayoclinic.org/diseases-conditions/acute-lymphocytic-leukemia/symptoms-causes/syc-20369077

2 Baljevic M, Jabbour E, O'Brien S, Kantarjian HM (2016). "Acute Lymphoblastic Leukemia".

3 Global Cancer Observatory. https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf

4 Leukaemia Care. Relapse in Acute Lymphoblastic Leukaemia (ALL). https://media.leukaemiacare.org.uk/wp-content/uploads/Relapse-in-Acute-Lymphoblastic-Leukaemia-ALL-Web-Version.pdf

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BeiGene Announces the Approval in China of BLINCYTO (Blinatumomab) for Injection for Adult Patients with Relapsed or Refractory B-Cell Precursor Acute...

Sutro Biopharma Presents Data from Ongoing Phase 1 Dose-Escalation Study for STRO-001 for the Treatment of B-cell Non-Hodgkin Lymphoma at the 62nd…

SOUTH SAN FRANCISCO, Calif., Dec. 7, 2020 /PRNewswire/ -- Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation cancer and autoimmune therapeutics, today announced a poster presentation at the virtual 62nd American Society of Hematology (ASH) Annual Meeting for the ongoing Phase 1 dose-escalation clinical trial for its CD74-targeted antibody drug conjugate (ADC) STRO-001 for patients with late-line Non-Hodgkin Lymphoma (NHL). Additionally, data were presented from preclinical studies conducted in collaboration with researchers from the Fred Hutchinson Cancer Research Center.

"With three product candidates in the pipeline actively enrolling patientsSTRO-001, STRO-002, our folate receptor alpha- (FolR) targeting ADC, and CC-99712 in partnership with Bristol Myers Squibb, a BCMA-targeting ADCSutro is working on addressing unmet needs via targeted therapies that can tackle cancer evolution," said Bill Newell, Sutro's Chief Executive Officer. "The encouraging safety and preliminary efficacy clinical data presented at ASH on STRO-001 for the treatment of late-line NHL further validates our platform and unique approach to ADC design, creating potential first-in-class and/or best-in-class therapeutic candidates."

STRO-001 Phase 1 Dose Escalation Interim DataSTRO-001-BCM1 is an ongoing first-in-human, phase 1 dose-escalation study evaluating the safety, tolerability, and preliminary antitumor activity of STRO-001 in adults with B-cell malignancies. The study is ongoing, and data presented at ASH included results from the NHL cohort. There were 21 NHL patients treated and 18 evaluable patients for response. Patients had a median of 5 prior therapies. 6/21 patients (29%) had previous stem cell transplant or CAR-T therapy. Data as of October 30, 2020 are as follows:

"These results continue to demonstrate the potential clinical benefit of STRO-001 treatment in patients with NHL who are heavily pretreated, with a median of five prior lines of treatment," said Dr. Arturo Molina, Sutro's Chief Medical Officer. "We are especially pleased for the patients who responded to STRO-001 after previously progressing on CAR-T treatments and an additional post- CAR-T regimen to which they had no response, seeing comparable duration of disease control to the duration on a cell therapy. STRO-001 has been well tolerated. We look forward to continuing the dose-escalation study to learn more about the potential for STRO-001 for patients with NHL."

Maximum tolerated dose (MTD) was not reached at 2.5 mg/kg. Active enrollment in the NHL cohort continues at the 3.5 mg/kg dose level and additional higher dose levels may be explored. The trial, registered with clinicaltrials.gov identifier NCT03424603, continues to enroll patients in dose escalation in both multiple myeloma (MM) and NHL cohorts.

The virtual poster titled "Preliminary Results of an Ongoing Phase 1 Dose Escalation Study of the Novel Anti-CD74 Antibody Drug Conjugate (ADC), STRO-001, in Patients with B-cell Non-Hodgkin Lymphoma," presented by Nirav N. Shah, M.D., Associate Professor of Medicine at Medical College of Wisconsin, is accessible through the Clinical/Scientific Presentation and Publication Highlights page of the News section of the company's website atwww.sutrobio.com.

Preclinical Data from Fred Hutchinson Cancer Research Center in Collaboration with SutroFred Hutchinson Cancer Research Center, in collaboration with Sutro, presented preclinical models showing the potential of CD74-targeted therapies, and in particular STRO-001, for the treatment of acute myelogenous leukemia (AML). The research is out of the lab of Soheil Meshinchi, M.D., Ph.D., Professor, Clinical Research Division at Fred Hutchinson Cancer Center and Professor of Pediatrics at University of Washington School of Medicine.

"My team at Fred Hutchinson Cancer Research Centerhas built arobustcomputational platform leveraging our large AML transcriptome dataset to identify highly expressedantigens on leukemic cells that are being targetedby agentsin early phase trials or preclinical developmentwith the goal ofrepurposing these therapeuticsfor use in AML,"said Soheil Meshinchi, M.D., Ph.D."One of these therapies wastheSTRO-001 ADC which targets the cell surface protein CD74. We have demonstrated that CD74 is highly expressed in a significant proportion of patients with AML. Our initial studies of STRO-001 ADC in AML cell lines demonstratedrobustinvitro cytotoxicity on AML cell lines expressing high-to moderate-levels of CD74, with no cytotoxicity in cells with no CD74 expression. This in vitro data, which identifies CD74 as a viable target in AML, coupled with the 27% incidence of CD74 in nearly 1,000 pediatric AML patients from our clinical trial with bortezomib, strengthens the notion that targeting CD74 with STRO-001 represents a viable targeted therapy in this patient population. In addition to AML, CD74 is highly expressed in high risk acute lymphoblastic leukemia (ALL), including Ph-positive and Ph-like ALL, thus providing rationale for exploring the efficacy of STRO-001 inall leukemias.

About Sutro Biopharma

Sutro Biopharma, Inc., located in South San Francisco, isa clinical-stage drug discovery, developmentand manufacturing company. Using precise protein engineering and rational design, Sutro is advancing next-generation oncology therapeutics.

Sutro's proprietary and integrated cell-free protein synthesis platform XpressCF and site-specific conjugation platform XpressCF+ led to the discovery of STRO-001 and STRO-002, Sutro's first two internally-developed ADCs. STRO-001 is a CD74-targeting ADC currently being investigated in a Phase 1 clinical trial of patients with advanced B-cell malignancies, including multiple myeloma and non-Hodgkin lymphoma. STRO-001 was granted Orphan Drug Designation by the FDA for multiple myeloma in October 2018. STRO-002 is a folate receptor alpha (FolR)-targeting ADC, currently being investigated in a Phase 1 clinical trial of patients with ovarian and endometrial cancers. This is the second product candidate to be evaluated in clinical trials resulting from Sutro's XpressCF and XpressCF+ technology platforms. A third program, CC-99712 (BCMA-targeting ADC), which is part of Sutro's collaboration with Bristol Myers Squibb (formerly Celgene Corporation), is enrolling patients for its Phase 1 clinical trial of patients with multiple myeloma. Sutro's proprietary technology was responsible for the discovery and manufacturing of CC-99712, for which Bristol Myers Squibb has worldwide development and commercialization rights. Sutro is entitled to development and regulatory milestone payments and tiered royalties from Bristol Myers Squibb for this BCMA ADC. Sutro is dedicated to transforming the lives of cancer patients by creating medicines with improved therapeutic profiles for areas of unmet need.

To date, Sutro's platform has led to cytokine-based immuno-oncology therapies, ADCs, vaccines and bispecific antibodies directed at precedented targets in clinical indications where the current standard of care is suboptimal. The platform allows it to accelerate discovery and development of potential first-in-class and best-in-class molecules through rapid and systematic evaluation of protein structure-activity relationships to create optimized homogeneous product candidates.

In addition to developing its own oncology pipeline, Sutro is collaborating with select pharmaceutical and biotech companies to discover and develop novel,next-generation therapeutics. As the pace of clinical development accelerates, Sutro and its partners are developing therapeutics designed to more efficiently kill tumors without harming healthy cells.

Additional multimedia content from Sutro regarding STRO-001 and STRO-002 can be foundhereandhere.

Follow Sutro on Twitter,@Sutrobio, and atwww.sutrobio.comto learn more about our passion for changing the future of oncology.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, anticipated preclinical and clinical development activities, timing of clinical trials and announcements of clinical results, potential benefits of the company's product candidates and platform and potential market opportunities for the company's product candidates. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Although the company believes that the expectations reflected in such forward-looking statements are reasonable, the company cannot guarantee future events, results, actions, levels of activity, performance or achievements, and the timing and results of biotechnology development and potential regulatory approval is inherently uncertain. Forward-looking statements are subject to risks and uncertainties that may cause the company's actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to the company's ability to advance its product candidates, the receipt and timing of potential regulatory designations, approvals and commercialization of product candidates, the impact of the COVID-19 pandemic on the Company's business, clinical trial sites, supply chain and manufacturing facilities, the Company's ability to maintain and recognize the benefits of certain designations received by product candidates, the timing and results of preclinical studies and clinical trials, the company's ability to fund development activities and achieve development goals, the company's ability to protect intellectual property, and the Company's commercial collaborations with third parties and other risks and uncertainties described under the heading "Risk Factors" in documents the company files from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and the company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof.

Investor Contact

Annie J. Chang Sutro Biopharma +1 650-255-8806 [emailprotected].com

Media ContactsDavid Schull Russo Partners (212) 845-4271 [emailprotected]

SOURCE Sutro Biopharma

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Sutro Biopharma Presents Data from Ongoing Phase 1 Dose-Escalation Study for STRO-001 for the Treatment of B-cell Non-Hodgkin Lymphoma at the 62nd...

Data from the ANDROMEDA Study Show Hematologic Response for DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) in Newly Diagnosed Light Chain (AL)…

RARITAN, N.J., Dec. 7, 2020 /PRNewswire/ --The Janssen Pharmaceutical Companies of Johnson & Johnson announced today new data from the Phase 3 ANDROMEDA study, which evaluated DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) as a treatment for patients withlight chain (AL) amyloidosis, a rare disease associated with deterioration of vital organs, most notably the heart, kidneys and liver, for which there are no currently approved therapies.1,2The data, which were featured in an oral presentation at the American Society of Hematology (ASH) 2020 Annual Meeting, showed a significantly higher complete hematologic response rate with DARZALEX FASPRO treatment in patients with this potentially fatal blood disorder compared to the standard regimen and consistent decreases in markers of disease, indicative of deep hematologic responses(Abstract #552).3

These data supported the recent submissionto theU.S. Food and Drug Administration (FDA) seeking approval for DARZALEX FASPRO in combination with bortezomib (VELCADE), cyclophosphamide and dexamethasone (D-VCd) for the treatment of patients with AL amyloidosis. The submission is being reviewed under the Real-Time Oncology Review Programto seek the first approval for any drug to treat this disease.4

"AL amyloidosis is a rare blood disorder in which abnormal proteins build up in the tissues and organs and eventually cause major organ deterioration," said study investigator, Raymond L. Comenzo, M.D., Director, John C. Davis Myeloma and Amyloid Program, Tufts Medical Center. "The data being presented at ASH show the potential of this new treatment regimen. Compared to VCd alone, the D-VCd regimen increased hematologicresponse rates and prolonged major organ deterioration-progression-free survival (MOD-PFS) in patients with AL amyloidosis."

Key Findings from the ANDROMEDA Oral Presentation (Abstract #552):

Additionally, D-VCd had an acceptable safety profile, consistent with that previously observed for each of the agents alone.

"AL amyloidosis is a challenging disease to diagnose and treat, with symptoms that mimic other conditions. During that delay, major organ deterioration can occur," said Jessica Vermeulen, M.D., Ph.D., Global Medical Head/Clinical Leader, Hematology & Oncology, Janssen Research & Development, LLC. "It is our hope that the ANDROMEDA study contributes to raising awareness of AL amyloidosis among patients and providers, and that approval of DARZALEX FASPRO, pending health authority reviews, will bring a much-needed and effective treatment option to patients."

Extent of cardiac involvement at baseline has a major impact on clinical outcomes for patients with AL amyloidosis.5A separate poster presentation of the ANDROMEDA data focused on the impact of cardiac involvement in newly diagnosed AL amyloidosis patients (Abstract #1392).6Results found that rates of hematologic, cardiac and renal response at six months were higher in the D-VCd group than the VCd group regardless of baseline cardiac stage (I, II or III), with more than 76 percent of these patients having a baseline cardiac stage of II or higher.6Additionally, both MOD-PFS and major organ deterioration-event-free survival(MOD-EFS) favored D-VCd across baseline cardiac stages.6

About the ANDROMEDA Study7ANDROMEDA (NCT03201965) is an ongoing Phase 3, randomized, open-label study investigating the safety and efficacy of daratumumab and hyaluronidase-fihj in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd), compared to VCd alone, for the treatment of patients with newly diagnosed light chain (AL) amyloidosis. The study includes 388 patients with newly diagnosed AL amyloidosis with measurable hematologic disease and one or more organs affected.

The primary endpoint is overall complete hematologic response rate by intent-to-treat (ITT). Secondary endpoints include MOD-PFS,MOD-EFS, organ response rate, overall survival and time to hematologic response, among others.

About DARZALEXFASPROIn August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab. Since launch, it is estimated that more than 150,000 patients have been treated with daratumumab worldwide.8 DARZALEX FASPROis the only CD38-directed antibody approved to be given subcutaneously to treat patients with multiple myeloma.

CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease.Daratumumabbinds to CD38 and inhibits tumor cell growth, causing myeloma cell death.9 Daratumumabmay also have an effect on normal cells.10 Data across nine Phase 3 clinical trials in multiple myeloma and AL amyloidosis, in both the frontline and relapsed settings, have shown that daratumumab-based regimens resulted in significant improvement in progression-free survival and/or overall survival.11,12,13,14,15,16,17,18 Additional studies are underway to assess the efficacy and safety of DARZALEX FASPROin the treatment of other malignant and pre-malignant hematologic diseases in which CD38 is expressed, including smoldering myeloma and light chain (AL) amyloidosis.19,20

For the full U.S. Prescribing Information, please visitwww.DARZALEX.com.

About AL AmyloidosisLight chain (AL) amyloidosis is a rare and potentially fatal hematologic disorder that can affect the function of multiple organs. The disease occurs when bone marrow produces abnormal pieces of antibodies called light chains, which clump together to form a substance called amyloid. These clumps of amyloid are deposited in tissues and vital organs and interfere with normal organ function, eventually causing organ deterioration.21,22 It is the most common type of amyloidosis. AL amyloidosis frequently affects the heart, kidneys, digestive tract, liver and nervous system, and is potentially fatal if left untreated.23 Diagnosis is often delayed and prognosis is poor due to advanced, multi-organ, particularly cardiac, involvement.24,25 Each year, an estimated 4,500 people develop AL amyloidosis in the U.S. alone.26

DARZALEX FASPRO is indicated for the treatment of adult patients with multiple myeloma:

DARZALEX FASPROTMIMPORTANT SAFETY INFORMATIONCONTRAINDICATIONSDARZALEX FASPROTMis contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase or any of the components of the formulation.

WARNINGS AND PRECAUTIONS

Hypersensitivity and Other Administration Reactions

Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPROTM.

Systemic Reactions

In a pooled safety population of 490patients who received DARZALEX FASPROTMas monotherapy or in combination, 11% of patients experienced a systemic administration-related reaction (Grade 2: 3.9%, Grade 3: 1.4%). Systemic administration-related reactions occurred in 10% of patients with the first injection, 0.2% with the second injection, and cumulatively 0.8% with subsequent injections. The median time to onset was 3.7hours (range: 9minutes to 3.5days). Of the 84systemic administration-related reactions that occurred in 52patients, 73(87%) occurred on the day of DARZALEX FASPROTM administration. Delayed systemic administration-related reactions have occurred in less than 1% of the patients.

Severe reactions included hypoxia, dyspnea, hypertension and tachycardia. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritis, chills, vomiting, nausea, and hypotension.

Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPROTM. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPROTMdepending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.

Local Reactions

In this pooled safety population, injection-site reactions occurred in 8% of patients, including Grade2 reactions in 0.6%. The most frequent (>1%) injection-site reaction was injection site erythema. These local reactions occurred a median of 7minutes (range: 0minutes to 4.7days) after starting administration of DARZALEX FASPROTM. Monitor for local reactions and consider symptomatic management.

NeutropeniaDaratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPROTMuntil recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPROTM, higher rates of Grade 3-4 neutropenia were observed.

ThrombocytopeniaDaratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Consider withholding DARZALEX FASPROTM until recovery of platelets.

Embryo-Fetal ToxicityBased on the mechanism of action, DARZALEX FASPROTMcan cause fetal harm when administered to a pregnant woman. DARZALEX FASPROTMmay cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPROTMand for 3months after the last dose.

The combination of DARZALEX FASPROTMwith lenalidomide is contraindicated in pregnant women, because lenalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide prescribing information on use during pregnancy.

Interference with Serological TestingDaratumumab binds to CD38 on red blood cells (RBCs) and results in a positive Indirect Antiglobulin Test (Indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type are not impacted.

Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPROTM. Type and screen patients prior to starting DARZALEX FASPROTM.

Interference with Determination of Complete ResponseDaratumumab is a human IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPROTM-treated patients with IgG kappa myeloma protein.

ADVERSE REACTIONSThe most common adverse reaction (20%) with DARZALEX FASPROTM monotherapy is: upper respiratory tract infection. The most common adverse reactions with combination therapy (20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, pyrexia, cough, muscle spasms, back pain, vomiting, upper respiratory tract infection, peripheral sensory neuropathy, constipation, and pneumonia.

The most common hematology laboratory abnormalities (40%) with DARZALEX FASPROTM are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.

Please see full Prescribing Information atwww.DARZALEX.com.

About the Janssen Pharmaceutical Companies of Johnson & Johnson At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

Learn more at http://www.janssen.com. Follow us at http://www.twitter.com/JanssenGlobal and http://www.twitter.com/JanssenUS.Janssen Research & Development, LLC and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

Cautions Concerning Forward-Looking StatementsThis press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding DARZALEX FASPROTM. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, or any of the other Janssen Pharmaceutical Companies,and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 29, 2019, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in the company's most recently filed Quarterly Report on Form 10-Q, and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at http://www.sec.gov, http://www.jnj.comor on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

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1National Organization for Rare Disorders. Amyloidosis. Accessed September 2020. https://rarediseases.org/rare-diseases/amyloidosis/. 2Lousada I, Comenzo RL, Landau H, et al. Light chain amyloidosis: patient experience survey from the Amyloidosis Research Consortium. Advances in Therapy. 2015;32(10):920-928. 3 Comenzo, RL et al. Reduction in Absolute Involved Free Light Chain and Difference Between Involved and Uninvolved Free Light Chain Is Associated with Prolonged Major Organ Deterioration Progression-Free Survival in Patients with Newly Diagnosed AL Amyloidosis Receiving Bortezomib, Cyclophosphamide, and Dexamethasone With or Without Daratumumab: Results From ANDROMEDA. Abstract #552. To be presented at 2020 American Society of Hematology Annual Meeting. 4 "Janssen Submits Application Seeking U.S. FDA Approval of DARZALEX FASPRO (Daratumumab and Hyaluronidase-Fihj) for the Treatment of Patients with Light Chain (AL) Amyloidosis." Janssen, 10 Sept. 2020, http://www.janssen.com/janssen-submits-application-seeking-us-fda-approval-darzalex-faspro-daratumumab-and-hyaluronidase. 5 Chaulagain CP, et al. Curr Hematol Malig Rep 2013;8:291-8. 6Minnema, MC et al. Outcomes by Cardiac Stage in Newly Diagnosed AL Amyloidosis: Results from ANDROMEDA. Abstract #1392. To be presented at 2020 American Society of Hematology Annual Meeting. 7Janssen Research & Development, LLC. A Study to Evaluate the Efficacy and Safety of Daratumumab in Combination With Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to CyBorD Alone in Newly Diagnosed Systemic Amyloid Light-chain (AL) Amyloidosis. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT03201965 Identifier: NCT03201965. 8Janssen World wide patients as of October 2020. 9European Medicines Agency. DARZALEX summary of product characteristics. Available at: https://www.ema.europa.eu/documents/product-information/darzalex-epar-productinformation_en.pdfLast accessed May 2020. 102020 Fedele G et al. CD38 Ligation in Peripheral Blood Mononuclear Cells of Myeloma Patients Induces Release of Protumorigenic IL-6 and Impaired Secretion of IFN Cytokines and Proliferation. Mediators Inflamm. 2013;564687. 11Janssen Research & Development, LLC. A Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02076009?term=mmy3003&rank=1 Identifier: NCT02136134. Last accessed: October 2020. 12Janssen Research & Development, LLC. Addition of Daratumumab to Combination of Bortezomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02136134?term=mmy3004&rank=1 Identifier: NCT02076009. Last accessed: October 2020. 13 Janssen Research & Development, LLC. A Study to Evaluate Daratumumab in Transplant Eligible Participants With Previously Untreated Multiple Myeloma (Cassiopeia). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02541383?term=mmy3006 Identifier: NCT02541383.Last accessed: October 2020. 14Janssen Research & Development, LLC. A Study of Combination of Daratumumab and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants With Previously Untreated Multiple Myeloma In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02195479?term=mmy3007&rank=1 Identifier: NCT02195479. Last accessed: October 2020. 15Janssen Research & Development, LLC. Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Participants With Previously Untreated Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02252172?term=mmy3008&rank=1 Identifier: NCT02252172. Last accessed: October 2020. 16Janssen Research & Development, LLC. A Study of VELCADE (Bortezomib) Melphalan-Prednisone (VMP) Compared to Daratumumab in Combination With VMP (D-VMP), in Participants With Previously Untreated Multiple Myeloma Who Are Ineligible for High-Dose Therapy (Asia Pacific Region). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT03217812?term=MMY3011&rank=1 Identifier: NCT03217812. Last accessed: October 2020. 17 European Myeloma Network. Compare Progression Free Survival Btw Daratumumab/Pomalidomide/Dexamethasone vs Pomalidomide/Dexamethasone (EMN14). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24] Available at: https://clinicaltrials.gov/ct2/show/NCT03180736?term=MMY3013&rank=2 Identifier: NCT03180736. Last accessed: October 2020. 18Amgen. Study of Carfilzomib, Daratumumab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma. (CANDOR). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24] Available at: https://clinicaltrials.gov/ct2/show/NCT03158688?term=NCT03158688&rank=1Identifier: NCT03158688. Last accessed: October 2020. 19Janssen Research & Development, LLC. A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants With Smoldering Multiple Myeloma In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 March 19]. Available at: https://clinicaltrials.gov/ct2/show/NCT03158688?term=NCT03158688&rank=1Identifier: NCT02316106. Last accessed: October 2020. 20Janssen Research & Development, LLC. An Efficacy and Safety Proof of Concept Study of Daratumumab in Relapsed/Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 March 19]. Available at: https://clinicaltrials.gov/ct2/show/NCT02413489?term=lym2001&rank=1 Identifier: NCT02413489. Last accessed: October 2020. 21National Organization for Rare Disorders. Amyloidosis. Accessed October 2020. https://rarediseases.org/rare-diseases/amyloidosis/. 22Lousada I, Comenzo RL, Landau H, et al. Light chain amyloidosis: patient experience survey from the Amyloidosis Research Consortium. Advances in Therapy. 2015;32(10):920-928. 23"AL Amyloidosis (Amyloid Light Chain)." Cleveland Clinic, my.clevelandclinic.org/health/diseases/15718- amyloidosis-al-amyloid-light-chain. 24Weiss BM, et al. J Clin Oncol. 2014;32(25):2699-2704. 25Palladini G, et al. J Clin Oncol. 2012;30:4541-49. 6. Muchtar E, et al. Blood. 2017;129(15):2111-2119. 26 Quock TP, Yan T, Chang E, Guthrie S, Broder MS. Epidemiology of AL amyloidosis: a real-world study using US claims data. Blood Adv. 2018;2(10):10461053. doi:10.1182/bloodadvances.2018016402 7 Kastritis, E. et al. Subcutaneous Daratumumab + Cyclophosphamide, Bortezomib, and Dexam.

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Data from the ANDROMEDA Study Show Hematologic Response for DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) in Newly Diagnosed Light Chain (AL)...