On November 5, 2020 bluebird bio, Inc. (Nasdaq: BLUE) reported that data from its gene and cell therapy programs for sickle cell disease (SCD), transfusion-dependent beta-thalassemia (TDT) and multiple myeloma (MM) will be presented, including seven oral presentations, at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place virtually from December 5-8, 2020 (Press release, bluebird bio, NOV 5, 2020, View Source [SID1234570119]).

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Updated results from patients in Group C of the company’s Phase 1/2 HGB-206 study of LentiGlobin for SCD gene therapy (bb1111) will be presented.

bluebird bio will also present updated long-term efficacy and safety results from the LTF-303 follow-up study; outcomes across genotypes; and outcomes in pediatric patients from Phase 3 studies HGB-207 and HGB-212 of betibeglogene autotemcel (beti-cel; formerly LentiGlobin for β-thalassemia) in TDT.

Data from across the company’s multiple myeloma program will be presented. Presentations will include updated safety and efficacy results from the Phase 1 CRB-401 clinical study of idecabtagene vicleucel (ide-cel, bb2121) and preliminary data from the ongoing Phase 1 CRB-402 clinical study of bb21217, as well as subgroup analyses of the pivotal Phase 2 KarMMa study of ide-cel. Ide-cel and bb21217 are investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immune therapies being studied, in partnership with Bristol-Myers Squibb, for the treatment of adult patients with MM.

Sickle Cell Disease Data at ASH (Free ASH Whitepaper)

Improvements in Health-Related Quality of Life for Patients Treated with LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy
Presenting Author: Julie Kanter, MD, University of Alabama at Birmingham, Birmingham, AL
Date/Time: Oral #365, Sunday, December 6, 2020, 9:45 am PST

Resolution of Serious Vaso-occlusive Pain Crises and Reduction in Patient-Reported Pain Intensity: Results from the Ongoing Phase 1/2 HGB-206 Group C Study of LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy
Presenting Author: Alexis A. Thompson, MD, Hematology Section Head, Ann & Robert H. Lurie Children’s Hospital, Chicago, IL
Date/Time: Oral #677, Monday, December 7, 2020, 1:30 pm PST

The GRNDaD Registry: Contemporary Natural History data and an analysis of real-world patterns of use and limitations of Disease Modifying Therapy in adults with SCD
Presenting Author: Alexandra Boye-Doe, MD, University of North Carolina School of Medicine, Chapel Hill, NC
Date/Time: Poster #1730, Sunday, December 6, 2020, 7:00 am – 3:30 pm PST

Transfusion-Dependent β-Thalassemia Data at ASH (Free ASH Whitepaper)

Long-Term Efficacy and Safety of Betibeglogene Autotemcel Gene Therapy for the Treatment of Transfusion-Dependent β-Thalassemia: Results in Patients with up to 6 Years of Follow-up
Presenting Author: Janet L. Kwiatkowski, MD, MSCE, Director, Thalassemia Center at Children’s Hospital of Philadelphia, Philadelphia, PA
Date/Time: Oral #153, Saturday, December 5, 2020, 12:00 pm PST

Favorable Outcomes in Pediatric Patients in the Phase 3 HGB-207 (Northstar-2) and HGB-212 (Northstar-3) Studies of betibeglogene autotemcel Gene Therapy for the Treatment of Transfusion-dependent β-thalassemia
Presenting Author: Alexis A. Thompson, MD, MPH, Hematology Section Head, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL
Date/Time: Oral #154, Saturday, December 5, 2020, 12:15 pm PST

Improvement in Erythropoiesis Following Treatment with Betibeglogene Autotemcel Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia in the Phase 3 HGB-207 Study
Presenting Author: John B. Porter, MA, MD, FRCP, FRCPath, Head of Red Cell Unit, University College London Hospital, London, UK
Date/Time: Poster #776, Saturday, December 5, 2020, 7:00 am – 3:30 pm PST

Response of patients with transfusion-dependent β-thalassemia (TDT) to betibeglogene autotemcel (beti-cel; LentiGlobin for β-thalassemia) gene therapy based on HBB genotype and disease genetic modifiers
Presenting Author: Mark C. Walters MD, Medical Director, Jordan Family Center for BMT & Cellular Therapies Research, UCSF Benioff Children’s Hospital Oakland, Oakland, CA
Date/Time: Poster #1699, Sunday, December 6, 2020, 7:00 am – 3:30 pm PST

Multiple Myeloma Data at ASH (Free ASH Whitepaper)

Updated results from the Phase I CRB-402 study of anti-BCMA CAR-T cell therapy bb21217 in patients with relapsed and refractory myeloma: correlation of expansion and duration of response with T cell phenotypes
Presenting Author: Melissa Alsina, MD, Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Date/Time: Oral #130, Saturday, December 5, 2020, 9:45 am PST

Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy, in patients with relapsed and refractory multiple myeloma: updated results from phase 1 CRB-401 study
Presenting Author: Yi Lin, MD, PhD, Division of Hematology, Mayo Clinic, Rochester, MN
Date/Time: Oral #131, Saturday, December 5, 2020, 10:00 am PST

Secondary Quality-of-Life Domains in Patients With Relapsed and Refractory Multiple Myeloma Treated With the BCMA-Directed CAR T Cell Therapy Idecabtagene Vicleucel (ide-cel; bb2121): Results from the KarMMa Clinical Trial
Author: Nina Shah, MD, University of California San Francisco, San Francisco, CA
Date/Time: Oral #437, Sunday, December 6, 2020, 12:15 pm PST

Efficacy and Safety of Idecabtagene Vicleucel (ide-cel, bb2121) in Elderly Patients with Relapsed/Refractory Multiple Myeloma: KarMMa Subgroup Analysis
Presenting Author: Jesús Berdeja, MD, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN
Date/Time: Poster #1367, Saturday, December 5, 2020, 7:00 am – 3:30 pm PST

Characterization of Cytokine Release Syndrome in the KarMMa Study of Idecabtagene Vicleucel (ide-cel, bb2121) For Relapsed and Refractory Multiple Myeloma
Presenting Author: Ankit Kansagra, MD, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX
Date/Time: Poster #1378, Saturday, December 5, 2020, 7:00 am – 3:30 pm PST

Molecular and Phenotypic Profiling of Drug Product and Post-infusion Samples from CRB-402, an Ongoing: Phase I Clinical Study of bb21217 a BCMA-directed CAR T Cell Therapy
Presenting Author: Olivia Finney, PhD, Associate Director, Immunotherapy, bluebird bio
Date/Time: Poster #1401, Saturday, December 5, 2020, 7:00 am – 3:30 pm PST

Effects of Prior Alkylating Therapies on Preinfusion Patient Characteristics and Starting Material for CAR T Cell Product Manufacturing in Late-Line Multiple Myeloma
Presenting Author: Julie Rytlewski, PhD, Bristol Myers Squibb, Princeton, NJ
Date/Time: Poster #1405, Saturday, December 5, 2020, 7:00 am – 3:30 pm PST

KarMMa-4: Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-Targeted CAR T Cell Therapy, in High-Risk Newly Diagnosed Multiple Myeloma
Presenting Author: Saad Z. Usmani, MD, Director, Clinical Research in Hematologic Malignancies, Levine Cancer Institute/Atrium Health, Charlotte, NC
Date/Time: Poster #1418, Saturday, December 5, 2020, 7:00 am – 3:30 pm PST

Healthcare Resource Utilization and Cost of Cytokine Release Syndrome and Neurologic Events in Patients with Relapsed and Refractory Multiple Myeloma Receiving the BCMA-directed CAR T Cell Therapy Idecabtagene Vicleucel (ide-cel, bb2121) in the KarMMa Trial
Presenting Author: Parmeswaran Hari, MD, Medical College of Wisconsin, Milwaukee, WI
Date/Time: Poster #1598, Saturday, December 5, 2020, 7:00 am – 3:30 pm PST

A Matching-Adjusted Indirect Comparison of Efficacy Outcomes for Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-directed CAR T Cell Therapy Versus Conventional Care in Triple-Class Exposed Relapsed and Refractory Multiple Myeloma
Presenting Author: Nina Shah, MD, University of California San Francisco, San Francisco, CA
Date/Time: Poster #1653, Saturday, December 5, 2020, 7:00 am – 3:30 pm PST

Idecabtagene Vicleucel (ide-cel, bb2121) Responses Are Characterized by Early and Temporally Consistent Activation and Expansion of CAR T Cells With a T Effector Phenotype
Presenting Author: Nathan Martin, PhD, Bristol Myers Squibb, Princeton, NJ
Date/Time: Poster #2315, Sunday, December 6, 2020, 7:00 am – 3:30 pm PST

KarMMa-3: A Phase 3 Study of Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-Targeted CAR T Cell Therapy Versus Standard Regimens in Relapsed and Refractory Multiple Myeloma
Presenting Author: Michel Delforge, MD, PhD, University Hospital Leuven, Leuven, Belgium
Date/Time: Poster #2323, Sunday, December 6, 2020, 7:00 am – 3:30 pm PST

Idecabtagene Vicleucel (ide-cel, bb2121) in Relapsed and Refractory Multiple Myeloma: Analyses of High-Risk Subgroups in the KarMMa Study
Presenting Author: Noopur S. Raje, MD, Massachusetts General Hospital, Boston, MA
Date/Time: Poster #3234, Monday, December 7, 2020, 7:00 am – 3:00 pm PST

Health State Utility Valuation in Patients with Triple-Class Exposed Relapsed and Refractory Multiple Myeloma Treated with the BCMA‑directed CAR T Cell Therapy, Idecabtagene Vicleucel (ide‑cel, bb2121): Results from the KarMMa Trial
Presenting Author: Michel Delforge, MD, PhD, University Hospital Leuven, Leuven, Belgium
Date/Time: Poster #3465, Monday, December 7, 2020, 7:00 am – 3:00pm PST

Abstracts outlining bluebird bio’s accepted data at ASH (Free ASH Whitepaper) are available on the ASH (Free ASH Whitepaper) conference website.

About LentiGlobin for SCD (bb1111)

SCD is a serious, progressive and debilitating genetic disease caused by a mutation in the β-globin gene that leads to the production of abnormal sickle hemoglobin (HbS), causing red blood cells (RBCs) to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and painful vaso-occlusive events (VOEs). For adults and children living with SCD, this means unpredictable episodes of excruciating pain due to vaso-occlusion as well as other acute complications—such as acute chest syndrome (ACS), stroke, and infections, which can contribute to early mortality in these patients.

LentiGlobin for SCD (bb1111) is an investigational gene therapy being studied as a potential treatment for SCD. bluebird bio’s clinical development program for LentiGlobin for SCD includes the ongoing Phase 1/2 HGB-206 study and the ongoing Phase 3 HGB-210 study.

LentiGlobin for SCD was designed to add functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once patients have the βA-T87Q-globin gene, their red blood cells can produce anti-sickling hemoglobin (HbA-T87Q) that decreases the proportion of HbS, with the goal of reducing sickled red blood cells, hemolysis and other complications.

As of March 3, 2020, a total of 37 patients have been treated with LentiGlobin for SCD to-date in the HGB-205 (n=3) and HGB-206 (n=34) clinical studies. The HGB-206 total includes: Group A (n=7), B (n=2) and C (n=25).

LentiGlobin for SCD received orphan medicinal product designation from the European Commission for the treatment of SCD, and Priority Medicines (PRIME) eligibility by the European Medicines Agency (EMA) in September 2020.

The U.S. Food and Drug Administration (FDA) granted orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation and rare pediatric disease designation for LentiGlobin for SCD. LentiGlobin for SCD continues to be evaluated in the ongoing Phase 1/2 HGB-206 and Phase 3 HGB-210 studies.

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-303) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for SCD. For more information visit: View Source or clinicaltrials.gov and use identifier NCT02633943 for LTF-303.

LentiGlobin for SCD is investigational and has not been approved in any geography.

About betibeglogene autotemcel

Transfusion dependent beta-thalassemia (TDT) is a severe genetic disease caused by mutations in the β-globin gene that result in reduced or significantly reduced hemoglobin (Hb). In order to survive, people with TDT require chronic blood transfusions to maintain adequate Hb levels. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.

Betibeglogene autotemcel (beti-cel) adds functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once a patient has the βA-T87Q-globin gene, they have the potential to produce HbA-T87Q, which is gene therapy-derived adult hemoglobin, at levels that may eliminate or significantly reduce the need for transfusions.

The European Commission granted conditional marketing authorization (CMA) for beti-cel, marketed as ZYNTEGLO gene therapy, for patients 12 years and older with transfusion-dependent β-thalassemia (TDT) who do not have a β0/β0 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate, but a human leukocyte antigen (HLA)-matched related HSC donor is not available.

As of March 3, 2020, a total of 60 pediatric, adolescent and adult patients, including 11 patients with at least 5 years of follow-up, across genotypes of TDT have been treated with beti-cel in the Phase 1/2 Northstar (HGB-204) and HGB-205 studies, and the Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies. In studies of beti-cel, patients were assessed for transfusion independence, defined as no longer needing red blood cell transfusions for at least 12 months while maintaining a weighted average Hb of at least 9 g/dL.

Non-serious adverse events (AEs) observed during clinical studies that were attributed to beti-cel included abdominal pain, thrombocytopenia, leukopenia, neutropenia, hot flush, dyspnoea, pain in extremity, tachycardia and non-cardiac chest pain. One serious adverse event (SAE) of thrombocytopenia was considered possibly related to beti-cel.

Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease. On April 28, 2020, the European Medicines Agency (EMA) renewed the CMA for beti-cel. The CMA for beti-cel is valid in the 27 member states of the EU as well as UK, Iceland, Liechtenstein and Norway. For details, please see the Summary of Product Characteristics (SmPC).

The U.S. FDA granted beti-cel orphan drug designation and Breakthrough Therapy designation for the treatment of TDT. Beti-cel is not approved in the United States. Beti-cel continues to be evaluated in the ongoing Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies.

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-303) for people who have participated in bluebird bio-sponsored clinical studies of beti-cel.

About idecabtagene vicleucel (ide-cel, bb2121)

Ide-cel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T cell immunotherapy. The ide-cel CAR is comprised of a murine extracellular single-chain variable fragment (scFv) specific for recognizing BCMA, attached to a human CD8 α hinge and transmembrane domain fused to the T cell cytoplasmic signaling domains of CD137 4-1BB and CD3-ζ chain, in tandem. Ide-cel recognizes and binds to BCMA on the surface of multiple myeloma cells leading to CAR T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells.

Ide-cel is being developed as part of a Co-Development, Co-Promotion and Profit Share Agreement between Bristol Myers Squibb and bluebird bio. Ide-cel was granted accelerated assessment by the European Medicines Agency (EMA) on March 26, 2020, and the Marketing Authorization Application (MAA) was validated by the EMA on May 20, 2020. The FDA accepted the ide-cel Biologics License Application (BLA) for priority review on September 22, 2020.

KarMMa (NCT03361748) is a pivotal, open-label, single-arm, multicenter, multinational, Phase 2 study evaluating the efficacy and safety of ide-cel in adults with RRMM in North America and Europe. The primary endpoint of the study is overall response rate as assessed by an independent review committee (IRC) according to the International Myeloma Working Group (IMWG) criteria. Complete response rate is a key secondary endpoint. Other secondary endpoints include time to response, duration of response, progression-free survival, overall survival, minimal residual disease evaluated by Next-Generation Sequencing (NGS) assay and safety. The study enrolled 140 patients, of whom 128 received ide-cel across the target dose levels of 150-450 x 106 CAR+ T cells after receiving lymphodepleting chemotherapy. All enrolled patients had received at least three prior treatment regimens, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and were refractory to their last regimen, defined as progression during or within 60 days of their last therapy.

CRB-401 (NCT02658929) is an open-label Phase 1 study evaluating the preliminary safety and efficacy of ide-cel in patients with relapsed and refractory multiple myeloma (RRMM). The primary endpoint of the study is safety. CRB-401 was designed as a two-part (dose escalation and dose expansion) study to determine the maximum tolerated dose and further evaluate the safety, tolerability and clinical activity at the recommended Phase 2 dose; these findings established the recommended dose of the Phase 2 KarMMa trial. All patients have been treated in the study and follow-up is ongoing.

In addition to the pivotal KarMMa and CRB-401 trials, bluebird bio and Bristol Myers Squibb’s broad clinical development program for ide-cel includes clinical studies (KarMMa-2, KarMMa-3, KarMMa-4) exploring ide-cel combinations and activity in earlier lines of treatment for patients with multiple myeloma, including newly diagnosed multiple myeloma. For more information visit clinicaltrials.gov.

Ide-cel is not approved for any indication in any geography.

About bb21217

bb21217 is an investigational BCMA-targeted CAR T cell therapy that uses the ide-cel CAR molecule and is cultured with the PI3 kinase inhibitor (bb007) to enrich for T cells displaying a memory-like phenotype with the intention to increase the in vivo persistence of CAR T cells. bb21217 is being studied for patients with multiple myeloma in partnership with Bristol Myers Squibb.

bluebird bio’s clinical development program for bb21217 includes the ongoing Phase 1 CRB-402 study. CRB-402 is the first-in-human study of bb21217 in patients with relapsed and refractory multiple myeloma (RRMM), designed to assess safety, pharmacokinetics, efficacy and duration of effect. CRB-402 is a two-part (dose escalation and dose expansion), open-label, multi-site Phase 1 study of bb21217 in adults with RRMM. For more information visit: clinicaltrials.gov using identifier NCT03274219.

bb21217 is not approved for any indication in any geography.

On November 5, 2020 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology both in vivo and ex vivo, reported operational highlights and financial results for the third quarter ended September 30, 2020 (Press release, Intellia Therapeutics, NOV 5, 2020, View Source [SID1234570118]).

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"We are very pleased with the recent regulatory authorization to begin our Phase 1 study of NTLA-2001, which keeps us on track to dose our first patient by year-end. This is an important step toward improving the lives of ATTR patients with a potentially curative treatment, and marks our transition into a clinical-stage company. Further, advancing NTLA-2001 is a major milestone for the field of genome editing, as this is the first clinical trial of a systemically delivered CRISPR/Cas9-based therapy," said Intellia President and Chief Executive Officer John Leonard, M.D. "In parallel, we are progressing NTLA-5001 and NTLA-2002 for the treatment of AML and HAE, respectively, each to an IND or equivalent regulatory submission next year. We also continue to develop innovative capabilities across our platform, based on the Nobel Prize-winning CRISPR/Cas9 technology, to generate our next wave of therapeutic candidates."

Third Quarter 2020 and Recent Operational Highlights

ATTR Program: Intellia recently announced the authorization of its Clinical Trial Application (CTA) by the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) to initiate a first-in-human clinical trial of NTLA-2001, an investigational therapy in development for the treatment of all clinical manifestations of ATTR. By applying the Company’s in vivo liver gene knockout technology, NTLA-2001 allows for the possibility of lifelong transthyretin (TTR) protein reduction after a single course of treatment. Intellia’s first-in-human study will evaluate NTLA-2001 in adults with hereditary ATTR with polyneuropathy (hATTR-PN). The Phase 1 study will be a two-part, open label, multi-center study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of NTLA-2001, which will include the measurement of serum TTR levels following a single intravenous infusion. Intellia is on track to dose its first patient by the end of 2020, subject to the impact of the COVID-19 pandemic, and is submitting additional regulatory applications in other countries as part of its ongoing, global development strategy. Once safety and an optimal dose have been determined in the first-in-human study, Intellia intends to further evaluate NTLA-2001 in a broader ATTR patient population of both polyneuropathy and cardiomyopathy patients. NTLA-2001 is part of a co-development/co-promotion agreement between Intellia, the lead development and commercialization party, and Regeneron Pharmaceuticals, Inc. (Regeneron).
AML Program: NTLA-5001 is a wholly owned, T cell receptor (TCR)-T cell therapy development candidate targeting the Wilms’ Tumor 1 (WT1) antigen for the treatment of AML. The Company seeks to develop NTLA-5001 as a broadly applicable treatment for AML patients, regardless of the mutational subtypes of the cancer. Intellia continues to advance Investigational New Drug application (IND)-enabling activities and remains on track to submit an IND or IND-equivalent for NTLA-5001 in the first half of 2021. At the upcoming 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place virtually from December 5 – 8, 2020, the Company will present new preclinical results in support of NTLA-5001, showing high anti-tumor activity of its lead WT1-directed TCR-T therapy in a mouse model of AML. The preclinical data will also highlight the advantages of its proprietary T cell engineering process to produce multiple, highly efficient sequential edits in T cells that have superior function and minimal translocations compared to results from standard T cell engineering approaches. Additional efforts are underway to evaluate the potential use of NTLA-5001 to treat WT1-positive solid tumors.
HAE Program: NTLA-2002 is a wholly owned, in vivo development candidate for the treatment of HAE. Today, Intellia announced results from its completed non-human primate (NHP) study of its lead lipid nanoparticle (LNP) formulation for NTLA-2002. Following a single dose, the knockout of the prekallikrein B1 (KLKB1) gene resulted in a year-long therapeutically relevant reduction of serum kallikrein protein levels and activity. Building on Intellia’s modular LNP delivery system, NTLA-2002 is designed to knock out the KLKB1 gene in the liver after a single course of treatment. This approach is expected to prevent improperly regulated bradykinin production and therefore reduce HAE attacks. During the third quarter, the Company initiated Good Laboratory Practices (GLP) toxicology studies in preparation for an IND or IND-equivalent submission for NTLA-2002, which remains on track for the second half of 2021.
Modular Platform: Intellia continues to make significant progress across its platform technologies, broadening the in vivo and ex vivo application of genome editing. This includes developing innovative CRISPR/Cas9-mediated targeted transgene insertion and allogeneic cell solutions. At the 16th Annual Meeting of the Oligonucleotide Therapeutics Society, held September 27-30, 2020, Intellia presented new data highlighting the potential to develop single-course therapies that may have a lifelong effect for a variety of genetic diseases. The data showed the persistence of both in vivo knockout and insertion CRISPR/Cas9 edits and corresponding durability of effect following a partial hepatectomy (PHx) and liver regrowth in a murine model. Unlike traditional gene therapy, for which a significant loss (over 80%) in transgene expression was observed in the insertion PHx model, Intellia’s targeted gene insertion approach yielded durable edits, with no significant loss in expression in the same model. Intellia and Regeneron are co-developing potential hemophilia A and B CRISPR/Cas9-based treatments using their jointly developed insertion capabilities. Intellia is also continuing to develop its proprietary platform to advance its wholly-owned programs.
Board of Directors: In October 2020, Intellia appointed John F. Crowley to its Board of Directors. Mr. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics, is a well-established leader in biotech and pharmaceuticals and a visionary advocate for the advancement of treatments for people living with rare diseases.
Scientific Co-Founder Awarded Nobel Prize: Jennifer Doudna, Ph.D., one of Intellia’s scientific co-founders, was awarded the 2020 Nobel Prize in Chemistry for inventing the revolutionary CRISPR/Cas9 genome editing technology. Dr. Doudna shares the award with her research collaborator, Dr. Emmanuelle Charpentier.
Upcoming Events

The Company will participate in the following events during the fourth quarter of 2020:

Credit Suisse Healthcare Conference, November 11, Virtual
Barclays Gene Editing and Therapy Summit, November 16, Virtual
62nd ASH (Free ASH Whitepaper) Annual Meeting, December 5-8, Virtual
Upcoming Milestones

The Company has set forth the following for pipeline progression:

ATTR: Dose first patient in Phase 1 study by year-end
AML: Submit an IND or IND-equivalent for NTLA-5001 in 1H 2021
HAE: Submit an IND or IND-equivalent for NTLA-2002 in 2H 2021
Third Quarter 2020 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $407.9 million as of September 30, 2020, compared to $284.5 million as of December 31, 2019. The increase was driven by net proceeds of $107.7 million from the June follow-on public offering, $100.0 million upfront payment from the Regeneron collaboration expansion, which included a $30.0 million equity investment, $14.7 million of net equity proceeds raised from the Company’s "At the Market" (ATM) agreement, $18.2 million of funding received under the Regeneron and Novartis collaborations and $2.7 million in proceeds from employee-based stock plans. These increases were offset in part by cash used to fund operations of approximately $119.8 million.
Collaboration Revenue: Collaboration revenue increased by $11.6 million to $22.2 million during the third quarter of 2020, compared to $10.6 million during the third quarter of 2019. The increase was mainly driven by a $15.3 million amount recognized for the transfer of control of the license to develop the Factor VIII target for hemophilia A associated with the extension of the Regeneron collaboration.
R&D Expenses: Research and development expenses increased by approximately $12.2 million to $39.8 million during the third quarter of 2020, compared to $27.5 million during the third quarter of 2019. This increase was primarily driven by the advancement of our lead programs, research personnel growth to support these programs, and the expansion of the development organization.
G&A Expenses: General and administrative expenses increased by approximately $2.1 million to $10.6 million during the third quarter of 2020, compared to $8.4 million during the third quarter of 2019. This increase was primarily related to employee related expenses, including stock-based compensation, of $2.0 million.
Net Loss: The Company’s net loss was $27.8 million for the third quarter of 2020, compared to $23.6 million during the third quarter of 2019.
Financial Guidance

Intellia expects that its cash, cash equivalents and marketable securities as of September 30, 2020 will enable the Company to fund its anticipated operating expenses and capital expenditure requirements for at least the next 24 months. This expectation excludes any strategic use of capital not currently in the Company’s base-case planning assumptions.

Conference Call to Discuss Third Quarter 2020 Earnings

The Company will discuss these results on a conference call today, November 5, 2020, at 8 a.m. ET.

To join the call:

U.S. callers should dial 1-877-317-6789 and international callers should dial 1-412-317-6789, approximately five minutes before the call.
All participants should ask to be connected to the Intellia Therapeutics conference call.
A replay of the call will be available through the Events and Presentations page of the Investors & Media section on Intellia’s website at www.intelliatx.com, beginning on November 5, 2020 at 12 p.m. ET.

On November 5, 2020 IGM Biosciences, Inc. (Nasdaq: IGMS), a clinical-stage biotechnology company focused on creating and developing engineered IgM antibodies, reported its financial results for the third quarter ended September 30, 2020 and provided an update on recent developments (Press release, IGM Biosciences, NOV 5, 2020, View Source [SID1234570117]).

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"We are very pleased with the progress that we have made through the first three quarters of 2020 in advancing our pipeline programs both in the clinic and in research," said Fred Schwarzer, Chief Executive Officer of IGM Biosciences. "Our lead IgM antibodies, IGM-2323 and IGM-8444, are moving forward in clinical trials, and we look forward to presenting initial, first-in-human clinical data from our Phase 1 trial of IGM-2323 at the upcoming ASH (Free ASH Whitepaper) Annual Meeting in December and to presenting initial clinical data from our Phase 1 trial of IGM-8444 in 2021."

Pipeline Updates:

IGM-2323

Phase 1 data to be presented at American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. IGM will report initial data from its Phase 1 clinical trial evaluating IGM-2323 in patients with relapsed/refractory Non-Hodgkin’s Lymphoma (NHL), the first-in-human application of IGM’s engineered IgM antibody technology, at the ASH (Free ASH Whitepaper) Annual Meeting being held virtually December 5-8, 2020.
IGM-8444

Initiated Phase 1 trial of IGM-8444. IGM announced that the first patient has been dosed in its Phase 1 clinical trial evaluating IGM-8444 in patients with solid cancers and NHL. IGM expects to report initial data from this Phase 1 trial in 2021.
IGM-7354

IGM-7354 preclinical data to be presented at Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting. The poster, titled "Targeting IL-15 delivery to PD-L1 Expressing Tumors using an Anti-PD-L1 x IL-15 Cytokine Fusion IgM to Enhance T Cell and NK Cell Mediated Tumor Cytotoxicity", will be made available online via the meeting’s virtual poster hall beginning on Monday, November 9 at 8:00 a.m. ET.

Corporate Updates:

Multi-year antibody discovery collaboration with AbCellera announced. IGM and AbCellera announced that they have entered into a multi-year, multi-target strategic research collaboration and license agreement intended to expedite discovery of novel IgM antibodies. AbCellera will generate panels of antibodies for multiple therapeutic targets identified by IGM using its full-stack, AI-powered antibody discovery technology, and IGM will have the rights to develop and commercialize the novel antibodies resulting from this collaboration.

Third Quarter 2020 Financial Results:

Cash and Investments: Cash and investments as of September 30, 2020 were $180.2 million, compared to $236.6 million as of December 31, 2019.
Research and Development (R&D) Expenses: For the third quarter of 2020, R&D expenses were $15.8 million, compared to $8.3 million for the same period in 2019.
General and Administrative (G&A) Expenses: For the third quarter of 2020, G&A expenses were $4.7 million, compared to $2.4 million for the same period in 2019.
Net Loss: For the third quarter of 2020, net loss was $20.3 million, or a loss of $0.66 per share, compared with a net loss of $10.2 million, or a loss of $2.41 per share, for the same period in 2019.
Shares Outstanding: Weighted-average shares outstanding for the third quarter of 2020 were 30.6 million, compared to 4.2 million for the same period in 2019.

2020 Financial Guidance:

IGM expects non-GAAP operating expenses for 2020 to be approximately $80 – $85 million, excluding estimated non-cash stock-based compensation expense of approximately $9 million. Including non-cash stock-based compensation expense, IGM estimates GAAP operating expenses for 2020 to be $89 – $94 million. IGM expects to end 2020 with a balance of over $140 million in cash and investments.

On November 5, 2020 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported financial results for the third quarter ended September 30, 2020, and provided a corporate update (Press release, BioCryst Pharmaceuticals, NOV 5, 2020, View Source [SID1234570116]).

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"We are 28 days from our PDUFA date and we are ready to launch ORLADEYO to bring HAE patients the oral, once-daily medicine they have been waiting for to prevent attacks, reduce their burden of therapy and live a normal life," said Jon Stonehouse, president and chief executive officer of BioCryst.

"In addition to this commercial transformation of the company, and the revenue it brings, our pipeline of BioCryst-discovered molecules continues to advance, with several upcoming near-term data readouts," Stonehouse added.

Program Updates and Key Milestones

Hereditary Angioedema (HAE) Program – ORLADEYO: Oral, once-daily treatment for prevention of HAE attacks

BioCryst expects three regulatory approvals for ORLADEYO in Q4 2020 and early 2021.

The U.S. Food and Drug Administration (FDA) is reviewing a new drug application for ORLADEYO and has set an action date of December 3, 2020, under the Prescription Drug User Fee Act (PDUFA).

In Japan, ORLADEYO is being reviewed under Sakigake designation. The Pharmaceutical and Medical Devices Agency (PMDA) has confirmed their regulatory review schedule and the company expects a decision on approval in December 2020.

On March 30, 2020, the company announced that the European Medicines Agency (EMA) had validated its marketing authorization application (MAA) submission for ORLADEYO and begun its formal review of the MAA under the centralized procedure. The company expects an opinion from the Committee for Medicinal Products for Human Use (CHMP) within approximately 12 months from MAA validation.
BioCryst has completed the build-out of the commercial infrastructure to support the successful launch of ORLADEYO in the U.S.

The company has hired and trained accomplished U.S. rare disease sales and market access teams and has deployed a robust patient services support hub.

The company is well-positioned in terms of product supply and inventory on-hand to support the launch and anticipated demand for ORLADEYO.

On October 30, 2020, the company announced that the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) has granted oral, once-daily berotralstat a positive scientific opinion through the Early Access to Medicines Scheme (EAMS). Under the EAMS, HAE patients in the UK aged 12 years and older can gain access to berotralstat for the routine prevention of recurrent attacks of HAE before the drug is granted marketing authorization by the European Commission. Medicines included in the EAMS are those that have a high unmet need, are intended to treat, diagnose or prevent seriously debilitating or life-threatening conditions where there are no adequate treatment options, and are likely to offer significant advantage over methods currently used in the UK.

On October 28, 2020, the company announced it will present five abstracts and one Distinguished Industry Oral Abstract, including 48-week results from the APeX-2 trial and new data on quality of life and the treatment burden of injectable medication administration, at the upcoming (virtual) Annual Scientific Meeting of the American College of Allergy, Asthma & Immunology on November 13-15.

On October 22, 2020, the company announced that data from the first 24 weeks of the APeX-2 trial of oral, once-daily berotralstat in patients with HAE have been published online by the Journal of Allergy and Clinical Immunology.
Complement Oral Factor D Inhibitor Program – BCX9930

The company is completing an ongoing dose ranging trial in treatment-naïve paroxysmal nocturnal hemoglobinuria (PNH) patients, and PNH patients with an inadequate response to C5 inhibitors.

Seven treatment-naïve PNH patients are currently receiving BCX9930, with four beyond 12 weeks of therapy, including two with more than 32 weeks on therapy. All seven treatment-naïve patients are continuing to benefit from BCX9930 treatment.

Based on the excellent results observed to-date at 400 mg bid and 500 mg bid, the company plans to add patients at these dose levels.

Because the acceleration of COVID-19 in the EU has slowed start-up of the inadequate responder cohorts, the company expects to report data from treatment-naïve and inadequate C5 responders dosed up to 500 mg bid in the first quarter of 2021.

On September 30, 2020, the company announced new data from treatment-naïve (no prior treatment with C5 inhibitors) PNH patients receiving doses of oral BCX9930 through 400 mg bid. Oral BCX9930 is driving rapid and dose-dependent reductions in key biomarkers, including LDH, and increasing hemoglobin levels in all PNH patients in the trial. Increases in hemoglobin levels were maintained without transfusions. BCX9930 has been safe and well tolerated at all doses in the trial. No drug-related serious adverse events have been reported.

On August 31, 2020, the company announced that the FDA has granted Orphan Drug designation for BCX9930, for the treatment of PNH. Orphan Drug designation qualifies BCX9930 for various development incentives, including tax credits for certain clinical costs, a waiver of the new drug application fee and a designated period of market exclusivity following approval.
Coronavirus Antiviral Program – Galidesivir (BCX4430)

Part 1 of a clinical trial of galidesivir in COVID-19 patients in Brazil has completed enrollment and the company expects to report results in the fourth quarter.

The primary endpoint of part 1 is safety. Data is also being collected on secondary endpoints, including clinical outcomes and virology. Based on recent conversations with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, the major funding partner for the program, the company understands that data from part 1 is a gating item for the program and some evidence of clinical and/or antiviral activity is important for the program to advance.
Additional Updates

The company remains on track to report data in Q4 2020 from its ongoing Phase 1 clinical trial of BCX9250, an oral ALK-2 kinase inhibitor for treatment of fibrodysplasia ossificans progressiva (FOP), in healthy subjects.

On September 3, 2020, the company announced that the U.S. Department of Health and Human Services (HHS) has exercised its option to purchase an additional 10,000 doses of BioCryst’s approved antiviral influenza therapy, RAPIVAB (peramivir injection), for approximately $7 million. The order is part of a $34.7 million contract (Contract No. 75D301-18-C-02984) the Centers for Disease Control and Prevention awarded in 2018 for the procurement of up to 50,000 doses of RAPIVAB (peramivir injection) over a five-year period for the strategic national stockpile.

Third Quarter 2020 Financial Results

For the three months ended September 30, 2020, total revenues were $6.1 million, compared to $1.8 million in the third quarter of 2019. The increase was primarily due to an increase in collaboration revenue under U.S. government development contracts and higher peramivir product sales to our commercial partners.

Research and development (R&D) expenses for the third quarter of 2020 increased to $30.2 million from $25.1 million in the third quarter of 2019, primarily due to increased spending on our complement-mediated diseases and galidesivir programs.

Selling, general and administrative (SG&A) expenses for the third quarter of 2020 increased to $17.2 million, compared to $11.7 million in the third quarter of 2019. The increase was primarily due to increased spending on commercial and medical affairs activities to support the U.S. commercial launch of ORLADEYO.

Interest expense was $2.9 million in the third quarter of 2020, compared to $3.0 million in the third quarter of 2019.

Net loss for the third quarter of 2020 was $46.1 million, or $0.26 per share, compared to a net loss of $37.6 million, or $0.34 per share, for the third quarter of 2019.

Cash, cash equivalents, restricted cash and investments totaled $148.5 million at September 30, 2020, and reflect an increase from $137.8 million at December 31, 2019. Operating cash use for the third quarter of 2020 was $43.1 million. Net operating cash use for the first nine months of 2020 was $98.0 million, as compared to $77.9 million for the first nine months of 2019.

Financial Outlook for 2020

BioCryst continues to expect full year 2020 net operating cash use to be in the range of $150 to $165 million, and its operating expenses to be in the range of $180 to $195 million. The company’s operating expense range excludes equity-based compensation expense due to the difficulty in reliably projecting this expense, as it is impacted by the volatility and price of the company’s stock, as well as by the vesting of the company’s outstanding performance-based stock options.

Conference Call and Webcast

BioCryst management will host a conference call and webcast at 8:30 a.m. ET today to discuss the financial results and provide a corporate update. The live call may be accessed by dialing 877-303-8027 for domestic callers and 760-536-5165 for international callers and using conference ID # 3766784. A live webcast of the call and any slides will be available online at the investors section of the company website at www.biocryst.com. A telephone replay of the call will be available by dialing 855-859-2056 for domestic callers or 404-537-3406 for international callers and entering the conference ID # 3766784.

On November 5, 2020 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biopharmaceutical company creating a new class of drugs based on targeted protein degradation, reported financial results for the third quarter ended September 30, 2020 and provided a corporate update (Press release, Arvinas, NOV 5, 2020, View Source [SID1234570114]).

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"Beginning the Phase 2 portion of the ARV-110 clinical trial marks another significant milestone for Arvinas," said John Houston, Ph.D., President and Chief Executive Officer at Arvinas. "Together with the expected initiation of a cohort expansion of ARV-471 in combination with a CDK4/6 inhibitor before the end of the year, we’re gratified by the strong momentum of our lead programs heading into 2021."

"When combined with our recent disclosure of five additional programs in our preclinical pipeline, these clinical milestones further validate our PROTAC Discovery Engine and the opportunity to create PROTAC degraders that meaningfully improve patient care," added Dr. Houston.

Business Highlights and Recent Developments

Dose escalation in each of the Phase 1/2 clinical trials of ARV-110 and ARV-471 continues.
Arvinas has initiated dosing at a first dose level in a Phase 2 cohort expansion for ARV-110.
The company announced platform updates and disclosed five additional programs from its preclinical pipeline. Arvinas’ portfolio encompasses a range of validated and undruggable targets in oncology, immuno-oncology, and neuroscience. The newly disclosed programs were B-cell lymphoma 6 protein (BCL6), Kirsten rat sarcoma (KRAS) protein, c-Myc, hematopoietic progenitor kinase 1 (HPK1), and mutant huntingtin (mHTT).
Arvinas entered into a collaboration and supply agreement with Pfizer in connection with a planned Phase 1b cohort expansion evaluating ARV-471 in combination with Pfizer’s Ibrance (palbociclib), an oral CDK4/6 inhibitor.
Anticipated Milestones and Expectations

2020 Milestones and Expectations

Arvinas expects to provide a program update for ARV-110, including a Phase 1 dose escalation update and an overview of the recently initiated Phase 2 dose expansion, in December 2020.
For the ARV-471 program, Arvinas expects to provide an update from its Phase 1 dose escalation in December 2020.
Arvinas expects to initiate a Phase 1b cohort expansion of ARV-471 in combination with Ibrance (palbociclib) in the fourth quarter of 2020. The study will evaluate the safety and tolerability of ARV-471 in combination with palbociclib and identify the recommended combination dose of ARV-471 for use with palbociclib.
2021 Milestones and Expectations

Arvinas expects to initiate the first of potentially two Phase 1b investigations of ARV-110 in combination with standard of care agents for mCRPC (e.g., abiraterone) in 2021.
Arvinas expects to share interim data from the Phase 2 dose expansion trial of ARV-110 in 2021.
Arvinas expects to initiate a Phase 2 dose expansion of ARV-471 in 2021.
Arvinas expects to share data from the Phase 1b cohort expansion of ARV-471 in combination with Ibrance (palbociclib) in the second half of 2021.
Arvinas expects to file an investigational new drug (IND) application for ARV-766, an androgen receptor degrader, in the first half of 2021.
Financial Guidance

Based on its current operating plan, Arvinas expects its cash, cash equivalents, and marketable securities will be sufficient to fund its planned operating expenses and capital expenditures into 2022.

Financial Highlights

Cash, Cash Equivalents, and Marketable Securities Position: As of September 30, 2020, cash, cash equivalents, and marketable securities were $248.6 million as compared with $280.9 million as of December 31, 2019. The decrease in cash, cash equivalents and marketable securities of $32.3 million for the first nine months of 2020 was primarily related to cash used for operations of $64.8 million and the purchase of lab equipment and leasehold improvements of $4.6 million, partially offset by net proceeds from the issuance of common stock and exercises of stock options of $33.1 million and $4.0 million received from two collaborators.

Research and Development Expenses: Research and development expenses were $30.0 million for the quarter ended September 30, 2020, as compared with $16.6 million for the quarter ended September 30, 2019. The increase in research and development expenses of $13.4 million for the quarter was primarily related to increases in clinical trials and chemistry, manufacturing and controls expenses associated with our AR program of $4.2 million and our ER program of $5.1 million, in addition to increases in expenses of $4.1 million associated with exploratory programs and investments in platform research.

General and Administrative Expenses: General and administrative expenses were $9.3 million for the quarter ended September 30, 2020, as compared with $8.0 million for the quarter ended September 30, 2019. The increase of $1.3 million was primarily related to an increase in personnel and facility related costs of $2.4 million, offset by a reduction in legal costs of $1.1 million.

Revenues: Revenue related to the license and rights to technology fees and research and development activities related to the collaboration and license agreement with Bayer (Bayer Collaboration Agreement) that was initiated in July 2019, the collaboration and license agreement with Pfizer (Pfizer Collaboration Agreement) that was initiated in January 2018, and the amended and restated option, license and collaboration agreement with Genentech that was initiated in November 2017 (collectively Collaboration Revenue) was $7.6 million for the quarter ended September 30, 2020, as compared with $5.4 million for the quarter ended September 30, 2019. The increase in Collaboration Revenue of $2.2 million primarily related to the revenues from the Bayer Collaboration Agreement and the Pfizer Collaboration Agreement. Total revenue of $30.1 for the three months ended September 30, 2019 included $24.7 million for the contribution of a license to Oerth Bio LLC (the Joint Venture).

Loss from Equity Method Investment: Loss from equity method investment for the quarter ended September 30, 2019 was $24.7 million. This loss was generated from the Joint Venture’s expensing the values associated with the contributed intellectual property from the Joint Venture partners.

Net Loss: Net loss was $30.8 million for the quarter ended September 30, 2020, as compared with $17.7 million for the quarter ended September 30, 2019. The increase in net loss for the quarter was primarily due to increased research and development expenses and increased general and administrative expenses.

About ARV-110
ARV-110 is an orally bioavailable PROTAC protein degrader designed to selectively target and degrade the androgen receptor (AR). ARV-110 is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer.

ARV-110 has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies.

About ARV-471
ARV-471 is an orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer.

In preclinical studies, ARV-471 demonstrated near-complete ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed superior anti-tumor activity when compared to a standard of care agent, fulvestrant, both as a single agent and in combination with a CDK4/6 inhibitor.