On November 9, 2020 Neoleukin Therapeutics, Inc., "Neoleukin" (NASDAQ:NLTX), a biopharmaceutical company utilizing sophisticated computational methods to design de novo protein therapeutics, reported financial results and a corporate update for the third quarter ended September 30, 2020 (Press release, Neoleukin Therapeutics, NOV 9, 2020, View Source [SID1234570302]).

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"The past quarter has been highly productive at Neoleukin as we continue to advance NL-201 toward an IND and prepare to initiate our first clinical trial in patients with advanced cancer," said Jonathan Drachman, M.D., Chief Executive Officer of Neoleukin. "This represents an important step for Neoleukin and for the field of de novo protein design. In addition, we recently disclosed details about NL-CVX1, a de novo protein designed to bind the spike protein of SARS-CoV-2 and to block viral infection of mammalian cells. These data, published in the journal Science, demonstrate the broad applicability and speed of our de novo design platform to address serious biological problems."

Recent Updates

NL-201 – IND on Track, CTN Application Submission in Australia

Neoleukin remains focused on its efforts to submit an Investigational New Drug (IND) application for its lead immunotherapy therapeutic candidate, NL-201, an IL-2 and IL-15 agonist, during the fourth quarter of 2020. At this time, Neoleukin does not expect a delay in the submission of its IND due to COVID-19 but acknowledges the potential exists for this timing to be impacted. In addition, the company has submitted a Clinical Trial Notification (CTN) application for NL-201 in Australia. The planned first-in-human clinical trials for NL-201 will test intravenous, monotherapy in patients with advanced solid tumors to determine the safety and tolerability of various dosing regimens.

De Novo Protein Design for Coronavirus – NL-CVX1

In November 2020, Neoleukin announced the publication of its scientific work in the journal Science describing the creation of novel molecules designed to treat or prevent infection by SARS-CoV-2, the virus that causes COVID-19. As reported, the optimized, hyperstable proteins act as decoys that bind to the SARS-CoV-2 spike protein with high affinity, preventing its association with the viral receptor hACE2 and blocking cellular entry. The lead molecule, NL-CVX1 (CTC-445.2d) was shown to prevent infection of multiple human cell lines in vitro and to protect hamsters from serious consequences of SARS-CoV-2 infection when administered intranasally. Neoleukin is currently evaluating the possibility of advancing this molecule to clinical trials in humans.

These results demonstrate the potential of Neoleukin’s computational protein design platform and its scientific team to rapidly engineer de novo proteins that could potentially address a variety of biological problems.

Executive & Board Appointments

In September 2020, Neoleukin announced the appointment of Martin Babler, President and Chief Executive Officer of Principia Biopharma, Inc. (NASDAQ: PRNB), to the company’s Board of Directors. Mr. Babler brings decades of experience in business and commercial development, marketing and leadership in the biopharmaceutical industry.

In October 2020, Neoleukin announced the appointment of Holly K. Vance as General Counsel. Ms. Vance joins Neoleukin from the Bill & Melinda Gates Foundation, where she served as Associate General Counsel, working with the foundation’s Strategic Investment Fund with a focus in the life sciences sector. She previously served as partner in the Seattle office of the global law firm K&L Gates LLP.

Summary of Financial Results

Cash Position: Cash and cash equivalents totaled $201.2 million as of September 30, 2020, compared to $143.1 million as of December 31, 2019. The increase was primarily the result of Neoleukin’s July financing in which the company raised $71.3 million in net proceeds.

Based upon its current operating plan, Neoleukin believes that its cash-on-hand will be sufficient to fund operations into 2023.

R&D Expenses: Research and development expenses for the third quarter of 2020 increased to $6.2 million from $1.4 million for the third quarter of 2019. This increase resulted primarily from ongoing development of NL-201 and excludes $47.7 million of acquired in-process R&D in the third quarter of 2019.

G&A Expenses: General and administrative expenses for the third quarter of 2020 decreased to $3.9 million from $10.4 million for the third quarter of 2019. Higher G&A expenses in the third quarter of 2019 were primarily due to one-time severance costs and the recognition of stock-based compensation expense for certain options that vested as

a result of the merger between Neoleukin Therapeutics, Inc. ("Former Neoleukin") and Aquinox Pharmaceuticals, Inc. ("Aquinox").

Acquired in-process R&D: The acquired in-process research and development expense arose from the merger between Former Neoleukin and Aquinox in 2019 and was expensed immediately as management determined that the asset has no alternative future use in accordance with ASC 730.

Gain on Sale of Aquinox Canada: The gain relates to the sale of Aquinox Canada, a wholly owned subsidiary of the company, during the three months ended September 30, 2020. The gain of $7.8 million recognized is the total consideration of $8.2 million, less transaction costs of $0.4 million.

Net Loss: Net loss for the third quarter of 2020 was $2.2 million compared to a net loss of $59.1 million in the third quarter of 2019. The net loss in the third quarter of 2019 included the significant acquired in-process R&D recognized in the period. Furthermore, net loss was reduced in the third quarter of 2020 due to the recognition of the gain on sale of Aquinox Canada.

About NL-201

NL-201 is a de novo receptor agonist of the IL-2 and IL-15 receptors, designed to expand cancer-fighting CD8 T cells and natural killer (NK) cells without any bias toward cells expressing the alpha receptor subunit (CD25). Previously presented preclinical data has demonstrated the ability of NL-201 to stimulate and expand CD8+ and NK cells at very low doses with minimal impact on immunosuppressive regulatory T cells

On November 9, 2020 WindMIL Therapeutics, a clinical-stage company developing marrow-infiltrating lymphocyte (MILs) products for cancer immunotherapy, reported new data demonstrating the therapeutic promise for MILs as a potential cancer immunotherapy for a wide range of solid tumor indications at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting (Press release, WindMIL Therapeutics, NOV 9, 2020, View Source [SID1234570301]).

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In the study, bone marrow and blood samples were collected from patients with non-small cell lung cancer (NSCLC), prostate cancer, squamous cell carcinoma of the head and neck (SCCHN), glioblastoma (GBM) and breast cancer. Utilizing a 10-day proprietary process, MILs and peripheral blood lymphocytes (PBLs) were activated and expanded from all samples. T cell lineage-specific markers (CD3, CD4 and CD8) were characterized by flow cytometry pre-and post-expansion. Tumor antigen-specific T cells were detected in all of the expanded MILs (n=25) but none of the expanded PBLs. On average, 16.0% of CD4+ T cells and 26.8% of CD8+ T cells in MILs produced intracellular interferon-gamma (IFN-γ) following stimulation with matched tumor lysate-derived antigens. Additionally, expansion of MILs significantly increased the purity of T cells from 8.8–59.8% (mean 29.8%) in pre-expansion bone marrow to 92-99.6% (mean 96.3%) in post-expansion MILs.

"MILs were successfully grown for all solid tumor types evaluated, including NSCLC, prostate, SCCHN, GBM and breast cancer and expanded MILs from the bone marrow of all patients contained cytokine-producing shared tumor antigen-specific T cells. In contrast, the corresponding expanded PBLs from blood failed to show any detectable tumor-specific immune recognition," said Kimberly Noonan, PhD, Executive Vice President, Chief Scientific Officer and Co-Founder of WindMIL Therapeutics. "These data further underline our belief that MILs hold therapeutic promise across a wide range of solid tumor indications."

The bone marrow is a unique niche in the immune system to which antigen-experienced memory T cells traffic and are then maintained. WindMIL has developed a proprietary process to activate, transform and expand these memory T cells into MILs. Because memory T cells in bone marrow occur as a result of the immune system’s recognition of tumor antigens, MILs are specifically suited for adoptive cellular immunotherapy and directly eradicate or facilitate eradication of each patient’s unique cancer.

Don Hayden, chairman and chief executive officer of WindMIL, said, "This research builds on our momentum in developing MILs as a novel class of autologous cell therapies for cancer immunotherapy. We believe this study speaks to the compelling potential of MILs to become an important treatment option for patients with solid tumor cancers, a patient population broadly in need of more effective therapies."

A copy of the abstract can be viewed online through the SITC (Free SITC Whitepaper) website.

About Marrow-Infiltrating Lymphocytes (MILs)
Marrow-infiltrating lymphocytes (MILs) are manufactured through a proprietary process to activate, transform and expand T cells found in each patient’s bone marrow. Distinguishing features of bone marrow T cells include their memory phenotype, inherent antigen-specificity, higher CD8:CD4 ratio and ability to persist long term when compared to peripheral blood lymphocytes. Because memory T cells in bone marrow occur as a result of the immune system’s recognition of tumor antigens, MILs are specifically suited for adoptive cellular immunotherapy and directly eradicate or facilitate eradication of each patient’s unique cancer. MILs are being investigated in clinical studies as ‘non gene-modified’ therapeutics and are under development as an alternative and potentially superior cell source to peripheral blood T cells for CAR-T therapy (CAR-MILs). WindMIL believes that the unique aspects of the respective profiles of MILs and CAR-MILs position them in distinct areas of the oncology treatment landscape. WindMIL is currently studying the use of MILs to treat patients with non-small cell lung cancer, squamous cell carcinoma of the head and neck, breast cancer, glioblastoma, renal cell carcinoma, urothelial carcinoma, and plans to expand into other solid tumors. To date, more than 100 patients have received treatment with MILs and ongoing studies continue to build upon the favorable safety profile and promising efficacy seen in early development.

On November 9, 2020 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported that Jounce management will participate in a fireside chat at the Cowen 2020 IO Next Summit on Friday, November 13, 2020 at 12:15 p.m. ET (Press release, Jounce Therapeutics, NOV 9, 2020, https://ir.jouncetx.com/news-releases/news-release-details/jounce-therapeutics-participate-virtual-fireside-chat-cowen-2020 [SID1234570300]).

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A live webcast of the presentation will be available by visiting "Events & Presentations" in the Investors and Media section of the company’s website at www.jouncetx.com. A replay of the webcast will be archived for 30 days following the presentation.

On November 9, 2020 Hoffmann-La Roche reorted that investors and analysts to participate in our virtual event on Tuesday, 8 December, 2020, highlighting Roche data presented at the virtual American Society of Hematology (ASH) (Free ASH Whitepaper) 62nd Annual Meeting, from 5-8th December (Press release, Hoffmann-La Roche, NOV 9, 2020, View Source [SID1234570292]).

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On November 9, 2020 AstraZeneca reported that Calquence (acalabrutinib), a next-generation selective Bruton’s tyrosine kinase (BTK) inhibitor, has been approved in the European Union (EU) for the treatment of adult patients with chronic lymphocytic leukaemia (CLL), the most common type of leukaemia in adults (Press release, AstraZeneca, NOV 9, 2020, View Source [SID1234570289]).

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The approval by the European Commission was based on positive results from two Phase III clinical trials, ELEVATE-TN in patients with previously untreated CLL and ASCEND in patients with relapsed or refractory CLL.1,2 This follows a recommendation for approval by the Committee for Medicinal Products for Human Use of the European Medicines Agency in July 2020.

Paolo Ghia, MD, Director, Strategic Research Program on CLL, Università Vita-Salute San Raffaele in Milan, and investigator of the ASCEND Phase III trial, said: "One of our biggest hurdles in treating chronic lymphocytic leukaemia is finding tolerable treatment options that manage the disease long term, which typically impacts older patients with comorbidities. Today’s news marks great progress for patients in Europe, as the Phase III clinical trials for Calquence showed a significant improvement in comparison with current standard treatments."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "This approval represents a key development for patients in Europe who until now have had limited chemotherapy-free treatment options. As our first European approval in blood cancers, Calquence provides a new tolerable treatment option with uncompromised efficacy and the potential to positively impact the quality of life for thousands of patients living with chronic lymphocytic leukaemia."

In the ELEVATE-TN Phase III trial, Calquence combined with obinutuzumab and as monotherapy reduced the risk of disease progression or death by 90% and 80%, respectively, compared with standard chemo-immunotherapy treatment chlorambucil plus obinutuzumab, in patients with previously untreated CLL.1 In the ASCEND Phase III trial, 88% of patients with relapsed or refractory CLL taking Calquence remained alive and free from disease progression after 12 months compared with 68% of patients on rituximab combined with idelalisib or bendamustine.2 Data from the interim results of the trials were published in The Lancet and Journal of Clinical Oncology, respectively.

Calquence is approved for the treatment of CLL and small lymphocytic lymphoma in the US and is approved for CLL in several other countries worldwide. Calquence is also approved for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy in the US and several other countries. Calquence is not currently approved for the treatment of MCL in Europe.

As part of a broad development programme, Calquence is being assessed in more than 20 AstraZeneca-sponsored clinical trials for the treatment of patients with B-cell malignancies including CLL, MCL, diffuse large B-cell lymphoma (DLBCL), Waldenström’s macroglobulinaemia (WM), follicular lymphoma (FL), and other haematologic malignancies.

Chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in adults, with an estimated 105,000 new cases globally in 2016, and the number of people living with CLL is expected to grow with improved treatment as patients live longer with the disease.3,4,5,6 In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections. As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells, and platelets. This could result in anaemia, infection, and bleeding.4 B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.

ELEVATE-TN

ELEVATE-TN (ACE-CL-007) was a randomised, multicentre, open-label Phase III trial evaluating the safety and efficacy of Calquence in combination with obinutuzumab, a CD20 monoclonal antibody, or Calquence alone versus chlorambucil, a chemotherapy, in combination with obinutuzumab in previously untreated patients with CLL. Patients 65 years of age or older, or between 18 and 65 years of age with a total Cumulative Illness Rating Scale >6 or creatinine clearance of 30 to 69mL/min, were enrolled. In the trial, 535 patients were randomised (1:1:1) into three arms. Patients in the first arm received chlorambucil in combination with obinutuzumab. Patients in the second arm received Calquence (100mg approximately every 12 hours until disease progression or unacceptable toxicity) in combination with obinutuzumab. Patients in the third arm received Calquence monotherapy (100mg approximately every 12 hours until disease progression or unacceptable toxicity).1

The primary endpoint was progression-free survival (PFS) in the Calquence and obinutuzumab arm compared to the chlorambucil and obinutuzumab arm, assessed by an independent review committee (IRC), and a key secondary endpoint was IRC-assessed PFS in the Calquence monotherapy arm compared to the chlorambucil and obinutuzumab arm. Other secondary endpoints included objective response rate, time to next treatment and overall survival (OS).1

ASCEND

ASCEND (ACE-CL-309) was a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy of Calquence in patients with relapsed or refractory CLL. In the trial, 310 patients were randomised (1:1) into two arms. Patients in the first arm received Calquence monotherapy (100mg twice daily until disease progression or unacceptable toxicity). Patients in the second arm received investigator’s choice of either rituximab, a CD20 monoclonal antibody, in combination with idelalisib, a PI3K inhibitor, or rituximab in combination with bendamustine, a chemotherapy.2

The primary endpoint was PFS assessed by an IRC, and key secondary endpoints included physician-assessed PFS, IRC- and physician-assessed overall response rate and duration of response, as well as OS, patient-reported outcomes and time to next treatment.2

Calquence

Calquence (acalabrutinib) is a next-generation, selective inhibitor of BTK. Calquence binds covalently to BTK, thereby inhibiting its activity.7,8 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.7

As part of an extensive clinical development programme, AstraZeneca and Acerta Pharma are currently evaluating Calquence in more than 20 company-sponsored clinical trials. Calquence is being developed for the treatment of multiple B-cell blood cancers including CLL, MCL, DLBCL, WM, FL, and other haematologic malignancies.

AstraZeneca in haematology

Leveraging its strength in oncology, AstraZeneca has established haematology as one of four key oncology disease areas of focus. The Company’s haematology franchise includes two medicines approved by the US Food and Drug Administration and a robust global development programme for a broad portfolio of potential blood cancer treatments. Acerta Pharma serves as AstraZeneca’s haematology research and development arm. AstraZeneca partners with like-minded science-led companies to advance the discovery and development of therapies to address unmet need.

AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and haematology.

By harnessing the power of six scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.