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RTX-240, an Allogeneic Engineered Red Blood Cell Expressing 4-1BBL and IL-15TP, Promotes NK Cell Functionality In Vitro and In Vivo

On November 9, 2020 Rubius Therapeutics, Inc. (Nasdaq:RUBY), a clinical-stage biopharmaceutical company that is genetically engineering red blood cells to create an entirely new class of cellular medicines called Red Cell Therapeutics, reported the presentation of new preclinical data supporting its lead clinical oncology program, RTX-240, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, Rubius Therapeutics, NOV 9, 2020, View Source [SID1234570309]). The meeting is being held virtually from November 9-14, 2020.

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RTX-240 is an allogeneic, off-the-shelf Red Cell Therapeutic that is engineered to mimic the human immune system by stimulating adaptive and innate immunity to generate an anti-tumor immune response. Rubius Therapeutics is currently enrolling patients in the Phase 1/2 clinical trial of RTX-240 for the treatment of patients with relapsed/refractory or locally advanced solid tumors. In addition, RTX-240 is being evaluated in a second Phase 1 arm of the clinical trial for the treatment of patients with relapsed/refractory acute myeloid leukemia.

"The preclinical data presented at SITC (Free SITC Whitepaper) indicate that RTX-240 has the ability to potently activate and expand CD8 T cells and natural killer (NK) cells in vitro and in vivo," said Laurence Turka, M.D., chief scientific officer of Rubius Therapeutics. "In addition, the preclinical data demonstrated that RTX-240 promotes NK cell killing of a myeloid leukemia cell line, giving us confidence that these promising preclinical results may translate into clinical benefit for patients with relapsed/refractory acute myeloid leukemia, where the activation status of the NK cells is linked to clinical outcomes. Finally, our surrogate model of RTX-240 demonstrated significant expansion of CD8 T cells and NK cells in a colorectal cancer model and potent anti-tumor activity in a melanoma model – giving us added conviction that RTX-240 may be an effective treatment for relapsed/refractory or locally advanced solid tumors."

Data Summary

RTX-240, an Allogeneic Engineered Red Blood Cell Expressing 4-1BBL and IL-15TP, Promotes NK Cell Functionality In Vitro and In Vivo

RTX-240 is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to simultaneously present hundreds of thousands of copies of the costimulatory molecule 4-1BBL and IL-15TP (trans-presentation of IL-15 on IL-15Rα) on the cell surface in their native forms. RTX-240 is designed to stimulate innate and adaptive immunity by activating NK cells and T cells inside the patient’s body to generate an anti-tumor immune response. RTX-240 preclinical data demonstrated:
° RTX-240 led to increased CD8 T cell and NK cell expansion and activation in vitro compared to the combination of a 4-1BB agonist antibody plus recombinant IL-15 which was directly correlated with the percentage of 4-1BBL and IL-15TP expressed on the cell surface
° RTX-240 expanded CD56dim NK cells, a cell population with high cytotoxicity
° RTX-240 promoted NK cell-killing of a myeloid leukemia cell line, K562, and this was accompanied by increased NK cell degranulation and activation
° A murine surrogate for RTX-240, mRBC-240, promoted significant expansion of CD8 T cells and NK cells in vivo in a murine model of colorectal cancer (CT26)
° mRBC-240 demonstrated potent antitumor activity in a B16F10 melanoma model that was directly correlated with the expansion of terminally differentiated NK cells in the tumors
About the RTX-240 Clinical Trial
Rubius Therapeutics is enrolling patients in a Phase 1/2 open label, multicenter, multidose, first-in-human dose-escalation and expansion study of RTX-240. The study contains two Phase 1 dose escalation arms: one in patients with relapsed/refractory or locally advanced solid tumors and another in patients with relapsed/refractory acute myeloid leukemia. These two Phase 1 arms will determine the safety and tolerability, pharmacokinetics, maximum tolerated dose and a recommended Phase 2 dose and dosing regimen of RTX-240 in patients with solid tumors as well as in patients with relapsed/refractory AML. The trial will also assess the pharmacodynamics of RTX-240 measured by changes in T and NK cell number and function relative to baseline and anti-tumor activity in both patient populations. The study will include an expansion phase in specified tumor types during the Phase 2 portion of the solid tumor arm. The extent to which the COVID-19 pandemic may impact Rubius’ ability to enroll patients in the trial will depend on future developments.

About RTX-240
RTX-240 is an allogeneic cellular therapy product candidate that is being evaluated for the treatment of patients with relapsed/refractory or locally advanced solid tumors or relapsed/refractory acute myeloid leukemia. RTX-240 is engineered to simultaneously present hundreds of thousands of copies of the costimulatory molecule 4-1BBL and IL-15TP (trans-presentation of IL-15 on IL-15Rα) in their native forms and is designed to stimulate innate and adaptive immunity by activating NK cells and T cells inside the patient’s body to generate an anti-tumor immune response.

Neoleukin Therapeutics Announces Third Quarter 2020 Financial Results and Corporate Update

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]).

"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

WindMIL Therapeutics Presents New Marrow-Infiltrating Lymphocytes (MILs®) Data Demonstrating Broad Therapeutic Promise for Solid Tumor Cancers

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]).

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.

Jounce Therapeutics to Participate in a Virtual Fireside Chat at Cowen 2020 IO Next Summit

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]).

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.

Invitation to Roche’s virtual event on key hematology data presented at ASH 2020

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]).