On November 4, 2021 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology both in vivo and ex vivo, reported financial results for the third quarter ended September 30, 2021, and recent operational highlights (Press release, Intellia Therapeutics, NOV 4, 2021, View Source [SID1234594565]).

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"Intellia continues to make important progress toward advancing its full-spectrum genome editing pipeline. Today, we are pleased to share that we remain highly encouraged by the safety profile, consistency of TTR reduction and ongoing effect of NTLA-2001 in the Phase 1 study. We believe we are closing in on identifying the recommended therapeutic dose for NTLA-2001 in patients with ATTR amyloidosis with polyneuropathy for further evaluation in Part 2, a single-dose expansion cohort. Additionally, while it has long been our plan to develop NTLA-2001 for all forms of ATTR amyloidosis, we have decided to accelerate the evaluation of NTLA-2001 in patients with ATTR amyloidosis whose primary clinical manifestation is cardiomyopathy. Based on the strength of our interim dataset, we are now seeking regulatory feedback for inclusion of the ATTR-CM patient population in our current Phase 1 study. We look forward to sharing updates from this program in Q1 2022," said Intellia President and Chief Executive Officer John Leonard, M.D. "Beyond our lead program, we remain focused on advancing NTLA-2002 for HAE and NTLA-5001 for AML. We received regulatory clearance for both programs to initiate first-in-human studies and we expect those studies to begin later this year. Finally, we nominated two gene insertion development candidates – NTLA-3001, our wholly owned AATD program, and a Factor 9 gene insertion candidate for Hem B in collaboration with Regeneron. Our rapidly expanding pipeline is yet one more example of the benefits of our modular platform in generating novel and potentially curative treatment options for the patients we aim to serve."

Third Quarter 2021 and Recent Operational Highlights

In Vivo Program Updates

NTLA-2001 for ATTR amyloidosis: NTLA-2001 is the first systemically delivered CRISPR-based therapy to be dosed in a patient and has the potential to be a curative treatment for transthyretin (ATTR) amyloidosis. Delivered with the Company’s in vivo lipid nanoparticle (LNP) technology, NTLA-2001 offers the possibility of halting and reversing the disease by driving a deep, lifelong reduction in transthyretin (TTR) protein after a single dose. NTLA-2001 is part of a co-development/co-promotion agreement between Intellia, the lead party for this program, and Regeneron Pharmaceuticals, Inc. (Regeneron).
NTLA-2001 is completing the dose-escalation portion of the Phase 1 study to determine the recommended dose for evaluation in Part 2 of the study, a single-dose expansion cohort. During the third quarter, to more fully elucidate the dose-response relationship, Intellia began dosing of subjects in Cohort 4, evaluating NTLA-2001 in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) at the 0.7 mg/kg dose level.
Intellia accelerated the evaluation of NTLA-2001 for the treatment of patients with ATTR amyloidosis with cardiomyopathy (ATTR-CM). The Company is in discussions with regulatory authorities on a protocol amendment to expand the Phase 1 trial population to include patients with ATTR-CM.
Intellia now plans to present interim data from Part 1, the single-ascending dose portion, and to initiate Part 2, a single-cohort expansion, in the first quarter of 2022. Data to be presented at a company-sponsored event will be from all four cohorts in Part 1 and include safety and serum TTR knockdown for Cohorts 3 and 4, as well as an early look at durability across all cohorts.
In October, Intellia announced that NTLA-2001 received Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) for the treatment of ATTR amyloidosis.
NTLA-2002 for HAE: NTLA-2002 leverages Intellia’s proprietary in vivo LNP delivery technology to knock out the KLKB1 gene in the liver with the potential to permanently reduce total plasma kallikrein protein and activity, a key mediator of hereditary angioedema (HAE). This approach aims to prevent attacks for people living with HAE by providing continuous suppression of plasma kallikrein activity following a single dose and to eliminate the significant treatment burden associated with currently available HAE therapies.
In October, Intellia announced the authorization of its Clinical Trial Application (CTA) by the New Zealand Medicines and Medical Devices Safety Authority (MEDSAFE) to initiate a Phase 1/2 study evaluating NTLA-2002. Additionally, a CTA has been subsequently authorized by the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) for the first-in-human study of NTLA-2002.
Intellia intends to enroll the first patient in the first-in-human study by year-end. The Phase 1/2 study will evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of NTLA-2002 in adults with Type I or Type II HAE, and will leverage insights gained from the development of NTLA-2001 enabling this study to begin evaluating NTLA-2002 at a higher initial dose.
NTLA-3001 for AATD-associated lung disease: NTLA-3001 is Intellia’s first and wholly owned CRISPR/Cas9-mediated in vivo targeted gene insertion development candidate. It is designed with the aim to precisely insert a healthy copy of the SERPINA1 gene, which encodes the alpha-1 antitrypsin (A1AT) protein, with the potential to permanently restore expression of functional A1AT protein to therapeutic levels after a single dose. This approach seeks to address alpha-1 antitrypsin deficiency (AATD)-associated lung disease and eliminate the need for sub-optimal weekly IV infusions of A1AT augmentation therapy or transplant in severe cases.
Today, Intellia announced the nomination of a new development candidate, NTLA-3001 for treatment of AATD. At the 29th Annual Congress of the European Society of Gene & Cell Therapy (ESGCT), Intellia presented data showing that insertion of a healthy form of the SERPINA1 gene led to normal human A1AT levels in non-human primates (NHPs) which were durable through 52 weeks in an ongoing study. The Company is advancing towards Investigational New Drug (IND)-enabling activities for this program and continues to explore additional editing strategies for AATD.
Ex Vivo Program Updates

NTLA-5001 for AML: NTLA-5001 is an autologous T cell receptor (TCR)-T cell therapy engineered to target the Wilms’ Tumor 1 (WT1) antigen for the treatment of all genetic subtypes of acute myeloid leukemia (AML).
In September, Intellia announced that the U.S. FDA accepted its IND application for NTLA-5001.
Intellia intends to initiate patient screening by year-end for a Phase 1/2a study evaluating NTLA-5001 in adults with persistent or recurrent AML who have previously received first-line therapy.
Research and Corporate Updates

Modular Platform and Pipeline Expansion: Intellia is advancing its modular platform technologies to broaden the in vivo and ex vivo applications of genome editing. This includes progressing capabilities for innovative CRISPR/Cas9-mediated targeted transgene insertion, in vivo editing in multiple tissue types and an allogeneic approach for the development of "off-the-shelf" T cell therapies. These efforts support new therapeutic candidates and strategic business development partnerships for advancing treatments for genetic diseases, cancers and autoimmune diseases.
ESGCT Annual Congress: In October, Intellia presented new preclinical data demonstrating key platform capabilities.
Intellia shared the first data highlighting its proprietary allogeneic cell engineering platform, demonstrating it can prevent immune rejection of allogeneic T cells for application in TCR-T and CAR-T cell therapy. Intellia’s proprietary approach leverages a novel combination of sequential gene edits to shield the engineered cell therapy from host T and NK cell attack. It does not rely on long-term, aggressive immune suppression of patients or the knockout of a protein required for HLA class I expression, which are approaches currently employed by others to address the challenge of immune rejection of the allogeneic cell product. Intellia intends to nominate its first allogeneic cell therapy development candidate by the first half of 2022.
Intellia shared new data on its proprietary cell engineering process, demonstrating LNP-based delivery of CRISPR/Cas9 ex vivo allows for sequential editing of T cells with high efficiency, faster expansion and minimal translocations as compared to electroporation. The data support the ability of this platform to be used for a variety of targeting modalities, including CAR and TCRs, and to support both autologous and allogeneic T cell candidates. This LNP-based approach is being used for NTLA-5001.
Collaboration Updates:
In the third quarter, Intellia and Regeneron nominated a Factor 9 (F9) gene insertion development candidate for its Hemophilia B (Hem B) program, leveraging their jointly developed targeted transgene insertion capabilities to insert F9. This candidate is part of a co-development/co-funding agreement between Intellia and Regeneron, the lead party for this program. F9 is a gene that encodes for Factor IX (FIX), a blood-clotting protein that is missing or defective in Hem B patients. In preclinical studies, the companies demonstrated the first CRISPR/Cas9-mediated targeted transgene insertion in the liver of NHPs, which resulted in circulating FIX levels at or above those found in normal human plasma.
In October, the Company announced a strategic collaboration with SparingVision to develop novel genomic medicines utilizing Intellia’s proprietary CRISPR/Cas9 technology for the treatment of ocular diseases. As part of the collaboration, Intellia will receive an equity stake in SparingVision, option for exclusive U.S. commercialization rights for product candidates arising from two of three collaboration targets, and eligibility for development and commercial milestone payments as well as royalties on potential future sales of products arising from the collaboration. The companies will additionally research and develop novel self-inactivating AAV vectors and LNP-based approaches to address delivery of CRISPR/Cas9 genome reagents to the retina.
In July, the Company completed the formation of a new universal CAR-T cell therapy company, which Intellia launched in collaboration with Blackstone Life Sciences and Cellex Cell Professionals GmbH. The new company will combine clinical-stage universal CAR-T platforms with Intellia’s differentiated allogeneic cell engineering platform to develop therapies for immuno-oncology and autoimmune diseases.
Upcoming Events

The Company will participate in the following events during the fourth quarter of 2021:

Barclays Gene Editing & Gene Therapy Summit, November 15, Virtual
Evercore ISI 4th Annual HealthCONx Conference, December 1, Virtual
63rd ASH (Free ASH Whitepaper) Annual Meeting & Exposition, December 11-14, Atlanta, GA and Virtual
Upcoming Milestones

The Company has set forth the following for pipeline progression:

ATTR:
Report additional interim clinical data from Phase 1 study of NTLA-2001 in Q1 2022
Initiate Part 2, a single-dose expansion cohort, of Phase 1 study of NTLA-2001 in Q1 2022
HAE: Initiate enrollment in the first-in-human study of NTLA-2002 by year-end
AML: Initiate patient screening in the first-in-human study of NTLA-5001 by year-end
Pipeline Expansion: Nominate the Company’s first allogeneic development candidate by 1H 2022
Third Quarter 2021 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $1,148.7 million as of September 30, 2021, compared to $597.4 million as of December 31, 2020. The increase was driven by net proceeds of $648.3 million from a follow-on offering in Q3 2021, $45.3 million of net proceeds from the Company’s "At the Market" (ATM) agreement, $40.8 million in proceeds from employee-based stock plans, and $4.2 million of funding for a cost-sharing agreement received from Regeneron. These increases were offset in part by cash used to fund operations of approximately $187.3 million.
Collaboration Revenue: Collaboration revenue decreased by $15.0 million to $7.2 million during the third quarter of 2021, compared to $22.2 million during the third quarter of 2020. The decrease in collaboration revenue in 2021 was primarily driven by $15.3 million related to the transfer of control of the license to develop the Factor VIII target for hemophilia A that was recorded during Q3 2020.
R&D Expenses: Research and development expenses increased by $20.7 million to $60.5 million during the third quarter of 2021, compared to $39.8 million during the third quarter of 2020. This increase was primarily driven by the advancement of our lead programs, research personnel growth to support these programs, and expansion of the development organization.
G&A Expenses: General and administrative expenses increased by $8.1 million to $18.7 million during the third quarter of 2021, compared to $10.6 million during the third quarter of 2020. This increase was primarily related to employee related expenses, including stock-based compensation of $3.8 million.
Net Loss: The Company’s net loss was $71.6 million for the third quarter of 2021, compared to $27.8 million during the third quarter of 2020.
Conference Call to Discuss Third Quarter Earnings

The Company will discuss these results on a conference call today, Thursday, November 4, at 8 a.m. ET.

To join the call:

U.S. callers should dial 1-833-316-0545 and international callers should dial 1-412-317-5726, approximately five minutes before the call. All participants should ask to be connected to the Intellia Therapeutics conference call.
Please visit this link for a simultaneous live webcast of the 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 4 at 12 p.m. ET.

On November 4, 2021 Loxo Oncology at Lilly, a research and development group of Eli Lilly and Company (NYSE: LLY), reported that study investigators will present data from the pirtobrutinib development program at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting to be held December 11-14, 2021 in Atlanta, GA and virtually (Press release, Eli Lilly, NOV 4, 2021, View Source [SID1234594356]). Pirtobrutinib is an investigational, highly selective, non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor.

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The pirtobrutinib oral presentations will provide updated clinical data from the ongoing Phase 1/2 BRUIN clinical trial in previously treated chronic lymphocytic leukemia, small lymphocytic lymphoma, and mantle cell lymphoma. The submitted abstracts utilized a September 2020 data cut-off date, and the presentations will utilize a July 2021 data cut-off date.

Additionally, two real-world evidence database studies will be shared: the first on outcomes for patients with chronic lymphocytic leukemia previously treated with a covalent BTK inhibitor and a BCL2 inhibitor will be presented in a poster presentation and the second on outcomes for patients with mantle cell lymphoma following covalent BTK inhibitor therapy will be published as an online-only abstract.

The schedule for the oral and poster presentations are as follows:

Presentation title: Pirtobrutinib, A Highly Selective, Non-Covalent BTK Inhibitor in Previously Treated CLL/SLL: Updated Results from the Phase 1/2 BRUIN Study
Publication Number: 391
Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological I
Session Date and Time: Sunday, December 12, 2021, 9:30 a.m.- 11:00 a.m. ET
Presentation Time: 9:30 AM
Location: Georgia World Congress Center, B401-B402 and online
Presenter: Anthony R. Mato, M.D.

Presentation Title: Pirtobrutinib, A Highly Selective, Non-Covalent BTK Inhibitor in Previously Treated Mantle Cell Lymphoma: Updated Results from the Phase 1/2 BRUIN Study
Publication Number: 381
Session: 623. Mantle Cell, Follicular, and Other B-Cell Lymphomas: Clinical and Epidemiological: Front-line Induction Therapy and Novel Agents After Relapse
Session Date and Time: Sunday, December 12, 2021, 9:30 a.m. – 11:00 a.m. ET
Presentation Time: 10:00 AM
Location: Georgia World Congress Center, Thomas Murphy Ballroom 1-2
Presenter: Michael L. Wang, M.D.

Presentation Title: Outcomes for Patients with Chronic Lymphocytic Leukemia Previously Treated with a Covalent BTK Inhibitor and BCL2 Inhibitor in the United States: A Real-World Database Study
Publication Number: 3743
Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster III
Session Date: Monday, December 13, 2021
Presentation Time: 6:00 p.m. – 8:00 p.m. ET
Location: Georgia World Congress Center, Hall B5
Presenter: Anthony R. Mato, M.D.

About Pirtobrutinib (LOXO-305)
Pirtobrutinib is an investigational, highly selective, non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor. BTK plays a key role in the B-cell antigen receptor signaling pathway, which is required for the development, activation and survival of normal white blood cells, known as B-cells, and malignant B-cells. BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including chronic lymphocytic leukemia, mantle cell lymphoma, Waldenström macroglobulinemia, and marginal zone lymphoma. Currently available covalent BTK inhibitors irreversibly inhibit BTK and the long-term efficacy of these therapies can be limited by acquired resistance, most commonly through BTK C481 mutations. In rapidly growing tumors with inherently high rates of BTK turnover, resistance to covalent BTK therapies may be the result of incomplete target inhibition. Pirtobrutinib was designed to reversibly bind BTK, deliver consistently high target coverage regardless of BTK turnover rate, preserve activity in the presence of the C481 acquired resistance mutations, and avoid off-target kinases that have complicated the development of both covalent and investigational non-covalent BTK inhibitors. Interested patients and physicians can contact the Loxo Oncology at Lilly Physician and Patient BTK Clinical Trial Hotline at 1-855-LOXO-305 or email [email protected].

About the BRUIN Phase 1/2 Trial
This first-in-human, global, multi-center Phase 1/2 trial evaluates pirtobrutinib as a single agent in patients with previously treated chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or non-Hodgkin’s lymphomas (NHL). The trial includes a Phase 1 dose escalation phase and a Phase 2 dose expansion phase. The Phase 1 dose escalation enrolls patients with CLL/SLL or NHL who have received at least two prior lines of therapy and have progressed or are intolerant to standard of care. The dose escalation phase followed a "3+3" design with pirtobrutinib dosed orally in 28-day cycles. As dose cohorts were cleared, additional patients could enroll in cleared cohorts and intra-patient dose escalation was permitted. The primary objective of the Phase 1 portion of the trial is to determine the maximum tolerated dose and recommended Phase 2 dose. Key secondary objectives include measures of safety, pharmacokinetics, and anti-tumor activity (i.e. Overall Response Rate (ORR) and Duration of Response, as determined by appropriate histology-specific response criteria). In the Phase 2 dose expansion, patients are enrolled across various cohorts, depending on disease type and prior therapy. The primary endpoint for Phase 2 is ORR. Secondary endpoints include duration of response (DOR), overall survival (OS), safety, and pharmacokinetics (PK).

About Loxo Oncology at Lilly
Loxo Oncology at Lilly was created in December 2019, combining the Lilly Research Laboratories oncology organization and Loxo Oncology, which was acquired by Lilly in early 2019. Loxo Oncology at Lilly brings together the focus and spirit of a biotech with the scale and resources of large pharma, with the goal of rapidly delivering impactful new medicines for people with cancer. Our approach centers on creating new oncology medicines that unequivocally work early in clinical development and will matter to patients.

On November 4, 2021 Genmab A/S (Nasdaq: GMAB) reported that multiple abstracts evaluating several investigational medicines in the company’s pipeline, or created using Genmab’s innovative drug development platforms, will be presented at the 63rd Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper), being held at the Georgia World Congress Center, in Atlanta, GA, and virtually, December 11-14. The presentations will include data from the phase 1b/2 EPCORE NHL-2 clinical trial evaluating the safety and preliminary efficacy of epcoritamab (DuoBody-CD3xCD20) in various combinations for the treatment of patients with B-cell non-Hodgkin lymphoma (NHL). In addition, preliminary data from the phase 1b/2 EPCORE CLL-1 clinical trial, evaluating epcoritamab in patients with relapsed, refractory chronic lymphocytic leukemia (CLL), will be presented. Results from more than 20 clinical trials evaluating Janssen Biotech, Inc. (Janssen)’s daratumumab, the subcutaneous formulation of daratumumab, and Janssen’s bispecific programs leveraging Genmab’s DuoBody technology platform, will be presented.

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All abstracts accepted for presentation have been published on the ASH (Free ASH Whitepaper)website.

Epcoritamab is being co-developed by Genmab and AbbVie (NYSE: ABBV). Daratumumab is being developed by Janssen under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab, and the companies have a research and license agreement to create and develop bispecific antibodies using Genmab’s DuoBody technology platform.

"The data being presented at this year’s ASH (Free ASH Whitepaper) represent our focus on harnessing the power of antibodies to develop differentiated cancer treatments and our commitment to delivering new therapeutic options to patients through our own research and development and through industry partnerships," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "We are especially encouraged by the data from the early-stage epcoritamab clinical trials and look forward to seeing results from additional studies."

On Tuesday, December 14, at 2:00 PM EST (8:00 PM CET / 7:00 PM GMT), Genmab will host its 2021 Virtual R&D Update and ASH (Free ASH Whitepaper) Data Review. The event will be webcast live. Details, including the webcast link, will be available on Genmab’s website, www.genmab.com. This meeting is not an official program of the ASH (Free ASH Whitepaper) Annual Meeting.

Abstracts accepted for presentation at ASH (Free ASH Whitepaper) include:

Epcoritamab (DuoBody-CD3xCD20):

Subcutaneous Epcoritamab in Combination with R-CHOP in Patients with Previously Untreated High-Risk Diffuse Large B-cell Lymphoma: Preliminary Results from a Phase 1/2 Trial

Subcutaneous Epcoritamab in Combination with R2 (Rituximab and Lenalidomide) in Patients with Relapsed or Refractory Follicular Lymphoma: Preliminary Results from a Phase 1/2 Trial

Subcutaneous Epcoritamab in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Preliminary Results from the EPCORE CLL-1 Trial
Phase 3 Trial (EPCORE DLBCL-1) of Epcoritamab versus Standard of Care in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Daratumumab:

Daratumumab (DARA) with Bortezomib, Thalidomide, and Dexamethasone (VTd) in Transplant-Eligible Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM): Analysis of Minimal Residual Disease (MRD) Negativity in CASSIOPEIA Part 1 and Part 2
Efficacy of Daratumumab, Lenalidomide, and Dexamethasone Based on Lenalidomide Starting Dose in Transplant-ineligible Patients With Newly Diagnosed Multiple Myeloma and Impaired Renal Function From the Phase 3 MAIA Study
Subcutaneous Daratumumab With Bortezomib, Cyclophosphamide, and Dexamethasone (VCd) in Patients With Newly Diagnosed Light Chain (AL) Amyloidosis: 18-month Landmark Analysis of the Phase 3 ANDROMEDA Study
Pomalidomide and Dexamethasone With or Without Subcutaneous Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma: Updated Analysis of the Phase 3 APOLLO Study
Subcutaneous Daratumumab with Rapid Corticosteroid Tapering in Relapsed or Refractory Multiple Myeloma Patients: Part 3 Update of the Open-label, Multicenter, Phase 1b PAVO Study
Progression-free Survival Outcomes by Response Status for Bortezomib, Melphalan, and Prednisone With or Without Daratumumab in Newly Diagnosed Multiple Myeloma: Pooled Subgroup Analysis of OCTANS and ALCYONE
Daratumumab, Bortezomib, Melphalan, and Prednisone Versus Bortezomib, Melphalan, and Prednisone in Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma: Pooled Analysis of OCTANS and ALCYONE

About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to tumors to elicit an immune response towards malignant cells. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T cell mediated killing of lymphoma B cells.i CD20 is a clinically validated therapeutic target, and is expressed on many B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia.ii,iii Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ broad oncology collaboration.

About DARZALEX(daratumumab)
DARZALEX (daratumumab) is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration approval to treat certain multiple myeloma indications. Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. The subcutaneous formulation of daratumumab (daratumumab and hyaluronidase-fihj) is the first subcutaneous CD38 antibody approved for the treatment of certain multiple myeloma indications and the first and only approved treatment for certain patients with light-chain (AL) amyloidosis.iv,v,vi

Please see local country prescribing information for all labeled indication and safety information.

(Press release, Genmab, NOV 4, 2021, View Source [SID1234594373])

On November 4, 2021 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that new and updated data from its diverse hematology program in blood cancers and disorders will be presented at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting from December 11-14 in Atlanta, GA (Press release, Regeneron, NOV 4, 2021, View Source [SID1234594401]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"Our hematology portfolio continues to expand with multiple trials now underway to investigate our bispecific antibodies, RNA-based therapies and gene editing, among other approaches," said L. Andres Sirulnik, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Hematology at Regeneron. "Our diverse pipeline includes investigational medicines across several blood cancers including multiple myeloma and lymphoma, in addition to blood disorders such as paroxysmal nocturnal hemoglobinuria, aplastic anemia, amyloidosis and thrombosis. We continue to make progress across our hematology portfolio with eight assets currently in the clinic."

Regeneron data at ASH (Free ASH Whitepaper) include an oral presentation with updated Phase 1 results from the completed dose escalation for REGN5458, an investigational BCMAxCD3 bispecific antibody, in patients with heavily pre-treated multiple myeloma. REGN5458 has the potential to advance treatment for patients with relapsed refractory disease, and the Phase 2 portion of this trial is currently enrolling with registrational intent. In addition, Regeneron and collaborator Alnylam will share the first data from healthy volunteers for a novel investigational combination of Regeneron’s C5 antibody pozelimab and Alnylam’s C5-inhibiting siRNA cemdisiran. The combination is planned to be evaluated in patients with the rare blood disorder, paroxysmal nocturnal hemoglobinuria (PNH), and other complement-driven disorders.

Additional presentations will include updated Phase 2 data investigating pozelimab monotherapy in patients with PNH, as well as analyses of real-world quality of life and treatment preferences among patients with diffuse large B-cell lymphoma to inform Regeneron’s therapeutic development in this tumor type.

Investor Webcast Information
Regeneron will host a conference call and simultaneous webcast to share updates on the company’s hematology portfolio on Monday, December 13 at 4:30 PM ET. To access this call, dial (888) 660-6127 (U.S.) or (973) 890-8355 (International); conference ID 2668896. A link to the webcast may be accessed from the ‘Investors and Media’ page of Regeneron’s website at View Source A replay of the conference call and webcast will be archived on the company’s website for at least 30 days.

Regeneron Presentations at ASH (Free ASH Whitepaper):

— Oral presentation (#160): Early, deep, and durable responses, and low rates of cytokine release syndrome with REGN5458, a BCMAxCD3 bispecific monoclonal antibody, in a Phase 1/2 first-in-human study in patients with relapsed/refractory multiple myeloma (RRMM) (Jeffrey A. Zonder, M.D.: Saturday, December 11, 12:45 PM ET)

— Other presentations:

Poster #1128: Pozelimab, a human monoclonal antibody against complement factor C5, provided inhibition of intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria (Jun-Ho Jang, M.D., Ph.D: Saturday, December 11, 5:30-7:30 PM ET)
Poster #1998: Interim analysis of an open-label, ascending-dose, Phase 1 study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of the subcutaneously administered human monoclonal antibody pozelimab in combination with single doses of the subcutaneously administered siRNA cemdisiran in healthy volunteers (Tavé van Zyl, M.D.: Sunday, December 12, 6:00-8:00 PM ET)
Poster #4111: Real-world health-related quality of life in patients with diffuse large B-cell lymphoma: Comparisons with reference populations and by line of therapy (Qiufei Ma: Monday, December 13, 6:00-8:00 PM ET)
Online publication: Treatment preferences among patients with diffuse large B-cell lymphoma: A survey across western Europe and the United States of America (P. Connor Johnson)
The potential uses of REGN5458, pozelimab and cemdisiran described above are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.

About Regeneron in Hematology
At Regeneron, we’re translating more than three decades of biology expertise with our proprietary VelociSuite technologies to develop potentially paradigm-changing medicines for patients with diverse blood cancers and rare blood disorders.

Our blood cancer research is focused on bispecific antibodies that are being investigated both as monotherapies and in combination with each other and emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop customized and potentially synergistic cancer treatments.

Our research and collaborations to develop potential treatments for rare blood disorders include explorations in antibody medicine, gene editing using CRISPR and gene-knockout technologies, as well as investigational RNA-approaches that are being investigated for their ability to deplete abnormal proteins or block disease-causing cellular signaling.

For more information, visit View Source

On November 4, 2021 DYNAVAX TECHNOLOGIES CORPORATION (Nasdaq: DVAX), a biopharmaceutical company focused on developing and commercializing novel vaccines, reported financial results for the third quarter ended September 30, 2021 and provided a business update (Press release, Dynavax Technologies, NOV 4, 2021, View Source [SID1234594417]).

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"This quarter we continued to make strong progress with both our lead commercial vaccine, HEPLISAV-B, and our CpG 1018 vaccine adjuvant platform," commented Ryan Spencer, Chief Executive Officer of Dynavax. "Our belief in the significant value of both assets is reinforced by the continued growth in market share and revenue for HEPLISAV-B along with multiple positive data readouts for adjuvanted COVID-19 vaccine candidates demonstrating the capabilities of CpG 1018 to help drive efficacy and high levels of antibodies while maintaining a favorable tolerability profile. Strong execution on a thoughtful, timely strategy has resulted in $244 million in year-to-date total revenue and $215 million in cash flow from operations, generating approximately $414 million in cash and equivalents at the end of this quarter which further enables our ability to continue to make investments which we believe will drive long-term value."

THIRD QUARTER AND RECENT BUSINESS UPDATE

HEPLISAV-B [Hepatitis B Vaccine (Recombinant), Adjuvanted]

HEPLISAV-B achieved another quarterly high with $22.7 million in revenue during the third quarter of 2021, compared to $11.6 million for the third quarter 2020. This increase was primarily driven by continued success in the field targeted accounts. Market share in the accounts targeted by the field sales team increased to 33.5%, up from 23% in the third quarter of 2020. With a consistent seroprotection rate of over 90% across all patients and the only FDA-approved two-dose hepatitis B vaccine for adults that is completed in one month, in a market where three-dose compliance is known to be a significant challenge, the Company believes HEPLISAV-B can protect more adults against hepatitis B than all other competitor vaccines.

The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) at its November 2021 meeting voted unanimously to recommend that all adults 19 to 59 years of age should receive hepatitis B vaccination. This recommendation greatly simplifies the identification of patients who need a hepatitis B vaccine compared to the current risk-based recommendation, and significantly expands the number of adults in the United States who should be vaccinated against hepatitis B.

CpG 1018 (Vaccine Adjuvant)

The Company’s strategy to expand the use of its CpG 1018 adjuvant platform and proven technology in multiple modalities of vaccine development continued to generate positive results in the third quarter. Through global partnerships, multiple data read outs for late-stage clinical trials of COVID-19 vaccine candidates adjuvanted with CpG 1018 generated impressive efficacy, immunogenicity and tolerability results. These clinical results enhance the data supporting CpG 1018’s ability to help enable new and improved vaccines that are effective and well-tolerated.

Net product revenue for CpG 1018 adjuvant during the third quarter of 2021 was $84.3 million, compared to $1.7 million for the third quarter 2020. The increase was associated with commercial supply agreements for COVID-19 collaborations. With the meaningful progress made across our COVID-19 partnership portfolio, the Company now expects 2021 full-year CpG 1018 revenue to be approximately $375- $425 million.

In July, Medigen Vaccine Biologics Corporation received Emergency Authorization (EUA) from the Taiwan Food and Drug Administration for MVC-COV1901, their COVID-19 vaccine adjuvanted with CpG 1018, and began vaccinating Taiwan residents in late August.
In July, Dynavax and Biological E (Bio E) entered into a commercial supply agreement for the use of CpG 1018 adjuvant in the commercial production of Bio E’s subunit COVID-19 vaccine candidate, CORBEVAX. Upon completion of their Phase 2/3 clinical trial in India and subsequent EUA, Bio E stated India’s Union Ministry of Health has reserved 300 million doses of CORBEVAX.
In September, Clover Biopharmaceuticals reported positive data for their protein-based COVID-19 vaccine candidate, SCB-2019 (CpG 1018/Alum) adjuvanted with Dynavax’s CpG 1018, which achieved the primary and secondary efficacy endpoints in SPECTRA, a global pivotal Phase 2/3 clinical trial that enrolled over 30,000 participants. Vaccine efficacy was successfully demonstrated in an environment where 100% of SARS-CoV-2 strains observed in the efficacy analysis were variants. SCB-2019 (CpG 1018/Alum) demonstrated a favorable safety and tolerability profile. Subject to receiving Emergency Use Listing (EUL) from the World Health Organization (WHO), Clover said it plans to supply up to 414 million doses of its COVID-19 vaccine candidate globally through the COVAX Facility.
In September, Dynavax and the U.S. Department of Defense (DOD) executed an agreement for approximately $22 million over two and a half years to develop a recombinant plague vaccine adjuvanted with CpG 1018. Enrollment for the Phase 2 clinical trial is expected to commence in 2022.
In October, Valneva SE reported positive topline data for their inactivated whole virus COVID-19 vaccine candidate, VLA2001, adjuvanted with Dynavax’s CpG 1018, in Cov-Compare, a comparative immunogenicity PHASE 3 trial in approximately 4,000 adults. The trial successfully met both co-primary endpoints of superior neutralizing antibody titer levels compared to the active comparator vaccine, AstraZeneca’s AZD1222 (ChAdOx1-S), and neutralizing antibody seroconversion rate above 95%. VLA2001 was well-tolerated, demonstrating a statistically significant better tolerability profile compared to AZD1222.
Corporate Updates

In October, Scott Myers was appointed to Board of Director and elected Chairman.
Upcoming Milestones

Multiple CpG 1018 COVID-19 collaboration partners’ regulatory submissions for emergency or conditional use authorization are expected by the end of 2021 and may provide additional revenue opportunity in 2022.
Data from Tdap-1018 in the ongoing Phase 1 clinical trial for an improved tetanus, diphtheria, and acellular pertussis booster vaccine candidate adjuvanted with CpG 1018 are expected in the first quarter of 2022.
FINANCIAL RESULTS FOR THE THIRD QUARTER

Product Revenue, Net.

Total revenue for the third quarter of 2021 was $108.3 million.

HEPLISAV-B product revenue, net was $22.7 million in the third quarter of 2021 compared to $11.6 million in the same period in 2020.
CpG 1018 product revenue, net was $84.3 million in the third quarter of 2021 compared to $1.7 million in the same period in 2020. As CpG 1018 revenues are generally recorded upon shipment to a customer, there may be fluctuations in revenues between quarters, as shipments often consist of large-sized batches.
Cost of Sales – Product. Cost of sales – product for the third quarter 2021 increased to $60.1 million, compared to $4.0 million for the third quarter of 2020. The increase was primarily due to manufacturing costs for increased volumes of CpG 1018 and HEPLISAV-B sold to customers.

Research and Development Expenses (R&D). R&D expenses for the third quarter of 2021 decreased to $6.2 million, compared to $8.5 million for the third quarter of 2020. The decrease is primarily associated with certain non-recurring expenses incurred in the third quarter of 2020 associated with the wind-down of the Company’s legacy immuno-oncology business.

Selling, General and Administrative Expenses (SG&A). SG&A expenses for the third quarter of 2021 increased to $26.9 million, compared to $21.5 million for the third quarter of 2020. This increase is primarily driven by compensation and related personnel costs, including non-cash stock-based compensation, associated with higher headcount.

Income (loss) from Operations and Net Income (loss). Income from operations for the third quarter of 2021 was $16.1 million compared to a loss from operations of $13.8 million in the third quarter of 2020. Net loss for the third quarter of 2021 was $28.4 million compared to net income of $4.4 million for the third quarter of 2020.

Other income (expense). Other income (expense) includes the change in fair value of warrant liability which is a non-cash adjustment to fair value each reporting period. The change in fair value of warrant liability for the third quarter of 2021 resulted in a loss of $45.1 million, compared to a gain of $21.2 million in the third quarter of 2020.

Earnings per share. Basic and diluted net loss per share were ($0.24), for the third quarter of 2021, compared to basic net income per share of $0.04 and diluted net loss per share of ($0.15) in the third quarter of 2020.

Cash Position and cash flow from operations. Cash, cash equivalents and marketable securities totaled $414.2 million on September 30, 2021. Cash flow from operations for the nine months ended September 30, 2021 was approximately $215.0 million.

CONFERENCE CALL AND WEBCAST INFORMATION

Dynavax will hold a conference call today at 4:30 p.m. ET/1:30 p.m. PT. The live audio webcast may be accessed through the "Events & Presentations" page on the "Investors" section of the Company’s website at www.dynavax.com. Alternatively, participants may dial (866) 420-4066 or (409) 217-8237 and refer to conference ID 5994808. A replay of the webcast will be available for 30 days following the live event.

Please see Important Safety Information below.

For more information about HEPLISAV-B, visit View Source

About Hepatitis B

Hepatitis B is a viral disease of the liver that can become chronic and lead to cirrhosis, liver cancer and death. The hepatitis B virus is 50 to 100 times more infectious than HIV,I and transmission is on the rise. There is no cure for hepatitis B, but effective vaccination can prevent the disease.

In adults, hepatitis B is spread through contact with infected blood and through unprotected sex with an infected person. The U.S. Centers for Disease Control (CDC) recommends vaccination for those at high risk for infection due to their jobs, lifestyle, living situations and travel to certain areas.II Because people with diabetes are particularly vulnerable to infection, the CDC recommends vaccination for adults age 19 to 59 with diabetes as soon as possible after their diagnosis, and for people age 60 and older with diabetes at their physician’s discretion.III Approximately 20 million U.S. adults have diabetes, and 1.5 million new cases of diabetes are diagnosed each year.IV

About HEPLISAV-B

HEPLISAV-B is an adult hepatitis B vaccine that combines hepatitis B surface antigen with Dynavax’s proprietary Toll-like Receptor (TLR) 9 agonist CpG 1018 to enhance the immune response. Dynavax has worldwide commercial rights to HEPLISAV-B.

Important U.S. Product Information

HEPLISAV-B is indicated for prevention of infection caused by all known subtypes of hepatitis B virus in adults age 18 years and older.

Safety and effectiveness of HEPLISAV-B have not been established in adults on hemodialysis.

For full U.S. Prescribing Information for HEPLISAV-B, click here.

Important U.S. Safety Information (ISI)

Do not administer HEPLISAV-B to individuals with a history of severe allergic reaction (e.g., anaphylaxis) after a previous dose of any hepatitis B vaccine or to any component of HEPLISAV-B, including yeast. Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of HEPLISAV-B. Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to HEPLISAV-B. Hepatitis B has a long incubation period. HEPLISAV-B may not prevent hepatitis B infection in individuals who have an unrecognized hepatitis B infection at the time of vaccine administration. The most common patient reported adverse reactions reported within 7 days of vaccination were injection site pain (23% to 39%), fatigue (11% to 17%) and headache (8% to 17%).

Important EU/EEA Product Information

HEPLISAV B is indicated for active immunisation against hepatitis B virus infection (HBV) caused by all known subtypes of hepatitis B virus in adults 18 years of age and older.

The use of HEPLISAV B should be in accordance with official recommendations.

It can be expected that hepatitis D will also be prevented by immunization with HEPLISAV B as hepatitis D (caused by the delta agent) does not occur in the absence of hepatitis B infection.

For full EU/EEA. Prescribing Information for HEPLISAV-B, click here.

Important EU/EEA Safety information

Do not receive HEPLISAV B if you have had a sudden life-threatening, allergic reaction after receiving HEPLISAV B in the past, or if you are allergic to any of components of this vaccine, including yeast. Signs of an allergic reaction may include itchy skin, rash, shortness of breath and swelling of the face or tongue.

Appropriate medical treatment and supervision should be readily available in case of rare anaphylactic reactions following the administration of the vaccine.

The administration of HEPLISAV B should be postponed in subjects suffering from acute severe febrile illness.

Immunocompromised persons may have a diminished immune response to HEPLISAV B.

Because of the long incubation period of hepatitis B, it is possible for unrecognised HBV infection to be present at the time of immunisation. HEPLISAV B may not prevent HBV infection in such cases.

There are very limited data on the immune response to HEPLISAV B in individuals who did not mount a protective immune response to another hepatitis B vaccine.

As a precautionary measure, it is preferable to avoid the use of HEPLISAV B during pregnancy. Vaccination during pregnancy should only be performed if the risk-benefit ratio at the individual level outweighs possible risks for the fetus.

The most common patient-reported side effects reported within 7 days of vaccination were pain, swelling or redness at the injection site, feeling tired, headache, muscle aches, feeling unwell and fever.

About CpG 1018 Adjuvant

CpG 1018 is the adjuvant used in HEPLISAV-B. Dynavax developed CpG 1018 adjuvant to provide an increased vaccine immune response, which has been demonstrated in HEPLISAV-B. CpG 1018 adjuvant provides a well- developed technology and a significant safety database, potentially accelerating the development and large-scale manufacturing of novel or improved vaccines.