On November 5, 2021 Reven Holdings, Inc. ("Reven") is a privately held clinical stage biotechnology and pharmaceutical company dedicated to the discovery and development of novel treatment platforms for cancer, viral illnesses, including COVID-19 – and inflammatory disorders (Press release, Reven Holdings, NOV 5, 2021, View Source [SID1234594611]).

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Reven reported the publication of a peer-reviewed article in the prestigious medical journal Frontiers in Oncology. The article reports a systematic analysis of the antibody responses to COVID-19 vaccination in cancer patients. This analysis was completed in collaboration with the Hacettepe University Cancer Institute team in Ankara/Turkey and Ares Pharmaceuticals, LLC in St. Paul, MN. COVID-19 vaccine seroconversion rates (i.e., antibody development success) were substantially lower in patients with hematologic malignancies (example: leukemias and lymphomas) and cancer patients receiving chemotherapy or immunosuppressive treatments than controls who did not have cancer.

The article, "Antibody Responses to COVID-19 Vaccination in Cancer: A Systematic Review," has been published in Frontiers in Oncology, and it is available online. To view the online publication, click here: http://journal.frontiersin.org/article/10.3389/fonc.2021.759108/full?&utm_source=Email_to_authors_&utm_medium=Email&utm_content=T1_11.5e1_author&utm_campaign=Email_publication&field=&journalName=Frontiers_in_Oncology&id=759108

Citation: Guven DC, Sahin TK, Kilickap S and Uckun FM (2021) Antibody Responses to COVID-19 Vaccination in Cancer: A Systematic Review. Front. Oncol. 11:759108. doi: 10.3389/fonc.2021.759108

The corresponding author, Executive Vice-President for Global Medical Affairs and Chief Medical Officer of Reven, Dr. Fatih Uckun MD PhD, explained: "We are reporting the challenges for oncology patients in achieving adaptive immunity against COVID-19. This report illustrates the importance of developing effective treatments against high-risk COVID-19 and COVID-19-associated cytokine release syndrome (CRS) considering the poor performance of vaccinations in cancer patients. Reven’s clinical development efforts for our lead COVID-19 drug candidate RJX are aimed at reducing the risk of life-threatening complications of COVID-19 and accelerating the full recovery of high-risk patients, such as those with cancer."

"This paper illustrates the importance of our randomized trial to address unmet needs in COVID-19 therapy," added Peter Lange, the CEO of Reven.

Reven had recently announced the successful completion of Part 1 of the Two-Part, Two Cohort Multi-Center Phase I/II trial of RJX in hospitalized high-risk COVID-19 patients. 12 hospitalized adult patients with symptomatic high-risk COVID-19 pneumonia and abnormally elevated inflammation markers in the blood were treated with daily intravenous infusions of RJX in combination with standard of care. Nine (9) of the 12 patients, including 3 patients with hypoxemic respiratory failure, had shown rapid clinical recovery with normalization of the abnormally elevated inflammation markers in the blood and were discharged from hospital at a median of 5 days. All patients tolerated their RJX infusions without any side effects. An Independent Data and Safety Monitoring Board (DSMB) that oversees and acts independently from the Reven project team had reviewed the clinical data in all 12 patients, and approved the initiation of the randomized, double-blind Part 2 portion of the Phase 2 study.

10 patients have already been enrolled and dosed in the randomized, double-blind, placebo-controlled Part 2 portion of the Phase 2 study (ClinicalTrials.gov Identifier: NCT04708340; View Source). This FDA-approved controlled clinical trial is aimed at evaluating the efficacy and safety of RJX in side-by-side comparison with a placebo as an adjunct to standard of care in hospitalized COVID-19 patients. Michael Volk, Director and Chief Strategy Officer of Reven, stated, "We are excited about the rapid progress in our clinical program against COVID-19."

"We are expecting topline data from this very important study by end of 2021," said Brian Denomme, Reven’s President.

"We are diligently advancing the clinical development of RJX," said Fatih Uckun, MD PhD.

RJX is an intravenous (IV) formulation of a patented first-in-class pharmaceutical composition containing a specific mixture of antioxidant and anti-inflammatory ingredients that is being developed for more effective treatment of patients with inflammatory disorders, including COVID-19 patients with viral sepsis, multi-system inflammation, cytokine release syndrome (CRS), shock, ARDS, and multi-organ failure. The FDA-approved clinical trial is aimed at evaluating the efficacy and safety of RJX as an adjunct to standard of care in hospitalized COVID-19 patients, who have high-risk features for progression to severe disease and ARDS and patients with hypoxemic respiratory failure receiving either non-invasive positive pressure ventilation (NIPPV) or high flow oxygen, who have not yet developed ARDS to require mechanical ventilation. Since RJX is a potent anti-oxidant and anti-inflammatory agent that has been shown to reduce the tissue-level oxidative stress in multiple organs in animal models of severe systemic inflammation, shock, cytokine storm, and multiorgan failure, Reven hopes that it will contribute to prevention of progression of COVID-19 and its faster resolution in high-risk patients.

About Rejuveinix (RJX)

RJX is an intravenous (IV) formulation of physiologically compatible compounds that is being developed for more effective treatment of patients with sepsis, including COVID-19 patients with viral sepsis and acute respiratory distress syndrome (ARDS).

On November 5, 2021 The Jaime Leandro Foundation for Therapeutic Cancer Vaccines (JLF) and partners reorted the treatment of the first cancer patient with a personalized neoantigen vaccine through a self-pay compassionate use program (Press release, xCures, NOV 5, 2021, View Source [SID1234594659]).

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JLF is a 501(c)3 non-profit organization whose mission is to make personalized anticancer vaccines available to patients with limited or no treatment options. Although neoantigen vaccines are not currently FDA approved, preliminary data is supportive of their use via compassionate access.

Personalized neoantigen vaccines are directed at tumor-specific mutation targets called neoantigens and leverage vaccine technology approaches to boost immune responses to a patient’s tumor. Although personalized neoantigen vaccines are very promising and have shown a favorable safety profile, their development and administration are hampered by regulatory, intellectual property, and clinical science obstacles. JLF has therefore partnered with multiple companies and institutions to bring these promising neoantigen vaccines directly to patients and their physicians.

By accelerating progress, informing patients, and enabling treatment, JLF and partners have worked diligently to help cancer patients and their clinicians overcome limited access to cancer vaccines through traditional trials. JLF has partnered with Washington University School of Medicine in St. Louis to use their pVAC-Seq algorithm, an important technology for the selection of neoantigens in the design of the vaccines. Of the many instrumental partners, key steps of vaccine design, manufacture, and patient treatment are provided by ennov1, CSBio, and xCures.

"We are delighted that xCures’ backend technology, regulatory know-how, and partnerships, enable cancer patients to access novel treatments while providing important real-world data," said Mika Newton, CEO of xCures. "By partnering with JLF we enabled the use of a personalized neoantigen vaccine under compassionate use/expanded access."

"We are thrilled to collaborate with JLF, and partners to ensure efficient analysis, optimal vaccine design and secure storage through our cloud-based platform and genomic technology," said James Inglis-Jones, Chairperson of ennov1.

"It’s exciting to contribute with CSBio’s peptide and instrumentation manufacturing technology towards manufacturing a fully personalized anticancer peptide vaccine," stated the CEO of CSBio, Jason Chang.

After a long process starting in fall 2020, the FDA approved treatment for the first two patients in the Spring of 2021. "We are very pleased to announce the initiation of treatment of the first cancer patient at Providence Saint John’s Health Center in Santa Monica, CA under the care of Dr. Santosh Kesari," stated JLF President, William Hoos.

The patient’s husband praised this new pathway to treatment. "JLF and partners allowed us the option to pursue a treatment we wanted, a cancer therapy based on current research, trials, and science." said Brad C. Through cancer vaccines, we now have hope for more time, better chance for survival, and hopefully a roadmap for others to follow as well."

On November 5, 2021 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage, precision oncology biopharmaceutical company, reported the decision to terminate its phase 2 KEAPSAKE clinical trial based on a lack of clinical benefit observed in patients treated with telaglenastat in an interim analysis (Press release, Calithera Biosciences, NOV 5, 2021, View Source [SID1234594581]).

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"We are disappointed in this outcome for the KEAPSAKE trial, but it was a well-run study with an interim analysis that gave us an answer to an important clinical question. We also want to express our sincere gratitude to the patients who participated in the trial and their families, as well as the physicians who served as investigators for the trial and their site staff," said Susan Molineaux, PhD, chief executive officer of Calithera. "We remain committed to patients with difficult-to-treat cancers and will continue to advance our investigational targeted therapies for biomarker-specific patient populations. Our near-term clinical development plans include leveraging our clinical and biomarker expertise in the KEAP1/NRF2 pathway in the development of our mTORC1/2 inhibitor sapanisertib in squamous non-small cell lung cancer, as well as advancing the development of our SYK inhibitor mivavotinib in specific biomarker-defined populations of diffuse large B-cell lymphoma. In addition, we are continuing the development of our arginase inhibitor CB-280 for the treatment of cystic fibrosis."

The phase 2 randomized, placebo-controlled, double-blind KEAPSAKE study was designed to evaluate the safety and anti-tumor activity of telaglenastat plus standard-of-care chemoimmunotherapy as front-line therapy among patients with stage IV non-squamous non-small cell lung cancer (NSCLC) whose tumors have a KEAP1 or NRF2 mutation. At the time of unblinding on October 27, 2021, there were 40 patients randomized. The available efficacy data at unblinding, including investigator-assessed progression-free survival (PFS), did not demonstrate clinical benefit, and analysis of the data led to the conclusion that there was a very low probability for the study to achieve a positive result. No difference in safety profile was seen between the two arms. The company has communicated these findings to the U.S. Food & Drug Administration (FDA) and has voluntarily discontinued the phase 2 study with agreement from members of the KEAPSAKE Steering Committee. Calithera has no plans to continue the development of telaglenastat at this time. Calithera estimates the cost savings resulting from the discontinuation of this trial will be $10-15 million.

Webcast and Conference Call Information

Calithera will hold a webcast today, Friday, November 5 at 8:30 a.m. Eastern Time / 5:30 a.m. Pacific Time. To access the link to the webcast, which will be broadcast live in listen-only mode, or the subsequent archived recording, visit the Investors section of the Calithera website at

www.calithera.com. Alternatively, the call may be accessed by dialing (855) 783-2599 (domestic) or (631) 485-4877 (international) and referring to conference ID 9529058. The webcast will be recorded and available for replay on Calithera’s website for 30 days.

On November 5, 2021 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, 2021 (Press release, Neoleukin Therapeutics, NOV 5, 2021, View Source [SID1234594597]).

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"During the third quarter, we made progress with our NL-201 phase 1 clinical trial, initiating multiple additional sites in the United States, Australia, and Canada; we look forward to providing interim data in 2022," said Jonathan Drachman, M.D., Chief Executive Officer of Neoleukin. "In addition, we and our collaborators continue to generate preclinical data, demonstrating the potential for NL-201 in additional indications and novel regimens. Based on these data, we plan to initiate a second NL-201 clinical trial in patients with hematology malignancies next year."

"Furthermore, our presentation next week at the American College of Rheumatology Annual Meeting will highlight a de novo IL-2/IL-15 inhibitor we have developed that could have applications in inflammatory and autoimmune disorders."

Recent Updates

NL-201

NL-201 is a de novo protein therapeutic candidate, designed to mimic the therapeutic activity of natural cytokines IL-2 and IL-15, while potentially reducing the toxicities associated with high-dose IL-2. NL-201 is currently in a phase 1 clinical trial for patients with relapsed and refractory solid tumors. A second trial for patients with hematologic malignancies is expected to begin next year.

Executive Appointment

In September, Neoleukin announced the appointment of Bill Arthur, Ph.D., as Vice President and Head of Research. Dr. Arthur joins Neoleukin after a decade at Seagen Inc., where he served most recently as Senior Director & Head of Cancer Biology. Prior to Seagen, Dr. Arthur worked at Merck & Co. and Rosetta Inpharmatics.

Scientific Conference Presentations

In September, an oral presentation at IDWeek by Neoleukin scientists and collaborators demonstrated the potential of NL-CVX1 to prevent or treat SAR-CoV-2 related disease, including new variants of concern.

At the upcoming American College of Rheumatology Annual Meeting (taking place virtually November 5-9, 2021), Neoleukin will have an oral presentation, titled "Development of a Computationally Designed, Hyperstable Dual Inhibitor of the IL-2 and IL-15 Receptors: A Novel Therapeutic Candidate for Inflammatory Conditions" (Monday, Nov. 8 at 2 p.m.). The abstract highlights development of a potent and hyperstable protein that blocks signaling by endogenous IL-2 and IL-15.

Neoleukin and collaborators will present four abstracts at SITC (Free SITC Whitepaper) 2021:

Title: NL-201 Induces Inflammation in a ‘Cold’ Tumor Microenvironment through Upregulation of MHC-I, Expansion of the TCR Repertoire, and Potent Antitumor Activity when Combined with PD-1 Inhibition

Poster/Abstract Number: 716,
Date/Time: Saturday, November 13, 7 a.m. to 8:30 p.m., ET

Title: Intratumoral Administration of NL-201, an Alpha-Independent IL-2/15 Receptor Agonist, Inhibits the Growth of Both Injected and Uninjected Tumors in Preclinical Models

Poster/Abstract Number: 898,
Date/Time: Saturday, November 13, 7 a.m. to 8:30 p.m., ET

Title: A First-in-Human Phase 1 Study of NL-201 in Patients with Relapsed or Refractory Cancer (Trials in Progress)

Poster/Abstract Number: 509,
Date/Time: Friday, November 12, 7 a.m. to 8:30 p.m. ET

Title: ICT01, an Anti-BTN3A Monoclonal Antibody, and NL-201, an Alpha-Independent IL-2/IL-15 Agonist, Combine to Elicit a Potent Anti-Tumor Response by Synergistically Stimulating Vγ9Vδ2 T Cell Activation and Proliferation

Poster/Abstract Number: 563
Date/Time: Friday, November 12, 7 a.m. to 8:30 p.m. ET

Two abstracts have been submitted regarding NL-201 for the upcoming 63RD American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH 2021) taking place virtually and in person December 11-14, 2021, and one will be presented as a poster:

Title: The IL-2/IL-15 Mimetic NL-201 Prevents Myeloma Relapse after ASCT by Expanding Highly Cytolytic T Cells in the Bone Marrow that are Resistant to Exhaustion

Abstract number: 1609

Title: NL-201, a De Novo Agonist of IL-2 and IL-15 Receptors, Demonstrates Synergistic Antitumor Activity with Anti-PD-1 Checkpoint Inhibitor Therapy in a Preclinical Non-Hodgkin Lymphoma Model

Abstract number: 4560

To be published in the November supplemental issue of Blood.

Summary of Financial Results

Cash Position: Cash and cash equivalents totaled $154.9 million as of September 30, 2021, compared to $192.6 million as of December 31, 2020.

Based upon current internal infrastructure and pipeline initiatives, Neoleukin believes it has sufficient cash to fund operations into the second half of 2023.

R&D Expenses: Research and development expenses for the third quarter of 2021 increased to $9.9 million from $6.2 million for the third quarter of 2020. The increase was primarily due to increased expenses incurred from clinical trial activities related to Neoleukin’s lead product candidate, NL-201, personnel-related costs, and in connection with the advancement of other Neoleukin technologies.

G&A Expenses: General and administrative expenses for the third quarter of 2021 increased to $5.6 million from $3.9 million for the third quarter of 2020. The increase in general and administrative expenses was primarily due to increases in personnel-related costs and professional service fees as Neoleukin continues to grow its operations.

Gain on Sale of Aquinox Canada: The gain in the third quarter of 2020 relates to the sale of Aquinox Canada, a wholly owned subsidiary of Neoleukin. The gain of $7.8 million recognized was the total consideration of $8.2 million, less transaction costs of $0.4 million.

Net Loss: Net loss for the third quarter of 2021 was $15.4 million compared to a net loss of $2.2 million in the third quarter of 2020.

On November 4, 2021 2seventy bio, Inc., (NASDAQ: TSVT), an emerging immuno-oncology company reported its official launch as an independent, publicly traded company. 2seventy bio will trade on the Nasdaq Global Select Market, commencing tomorrow, November 5 under the ticker symbol "TSVT (Press release, bluebird bio, NOV 4, 2021, View Source [SID1234594629])."

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"We’ve done the intense work to reach the start line and we are extremely excited to officially introduce 2seventy bio. 2seventy was created from an unrelenting desire to find new ways to outmaneuver cancer and give more time to the people we serve," said Nick Leschly, chief kairos* officer, 2seventy bio. "Our organization is ready: from our bold and seasoned team to our deep scientific expertise and our strong financial foundation. Our commitment is to sustain the energy, passion and rigor that we have today as we establish the leading immuno-oncology cell therapy company with an aim to deliver transformative treatment options to people living with a range of difficult to treat cancers."

The company officially separates today from bluebird bio, Inc. and launches with a robust cell therapy pipeline across a range of hematologic and solid tumors including two candidates that are planned to enter the clinic in the first half of 2022. The portfolio also includes a development and 50/50 U.S. commercialization partnership with Bristol Myers Squibb (BMS) for ABECMA, a first-in-class, BCMA-directed CAR T cell immunotherapy for multiple myeloma approved in the U.S.

Unique Scientific Approach to Cell Therapy

"Our differentiated cell therapy platform is built around the goal of delivering therapies that provide significant benefit to people living with cancer," said Philip Gregory, chief scientific officer, 2seventy bio. "We begin with the foundational understanding that autologous CAR T cell therapy works, yet there’s room to build and improve. We identify the unmet medical need, and we strive to understand where there are unique opportunities to change the path of disease. We then undertake a deliberate process to devise an engineered solution that relies on the robust toolbox of targeting, signaling, and enhancement technologies that we have established through our extensive experience and partnerships across industry and academia. Importantly, we are uniquely positioned to deliver these therapies to patients through a development strategy that is designed to efficiently test our hypotheses and quickly deliver answers not only for a given program, but across the technologies. By taking this approach, we’re able to apply learnings across the platform in rapid succession."

2seventy bio’s cell therapy pipeline includes approaches to hematologic malignancies and solid tumors, including two clinical studies expected to be initiated in the first half of 2022:

Multiple Myeloma (MM):
ABECMA (idecabtagene vicleucel; ide-cel): ABECMA, a first-in-class, B-cell maturation antigen (BCMA)-directed CAR T cell immunotherapy approved in the U.S. for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody, is being jointly developed and commercialized with BMS in the U.S.1 ABECMA generated $67 million in U.S. sales in 3Q21, its first full quarter of launch and 2seventy bio and BMS are pursuing additional clinical studies in earlier lines of treatment for patients with MM.
bb21217: Data from the ongoing Phase 1 study of bb21217, a BCMA-directed CAR T cell therapy in patients with relapsed and refractory MM that uses the ide-cel CAR molecule and is cultured with a 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, to be presented by the end of 2021.
Next-generation: In addition, the company is exploring a next-generation approach that utilizes the experience applying the first commercial CAR T cell in MM to aid the design of a novel autologous T cell approach.
Acute Myeloid Leukemia (AML)/SC-DARIC33: The initiation of an upcoming Phase 1 study of SC-DARIC33 in relapsed/refractory pediatric and young adult AML in collaboration with Seattle Children’s Therapeutics will be a first-in-human investigation of 2seventy bio’s proprietary Dimerizing Agent Regulated Immunoreceptor Complex (DARIC) T cell platform.
B-cell non-Hodgkins Lymphoma (bNHL)/bbT369: The initiation of an upcoming Phase 1 dose-escalation study in patients with relapsed and refractory bNHL will be a proof-of-concept study of 2seventy bio’s proprietary gene editing platform, dual-targeting strategies and split co-stimulation signaling technology.
Solid Tumors: Pre-clinical studies are underway utilizing 2seventy bio’s diversified and innovative toolbox, including a program targeting MAGEA4, a surface antigen that is highly expressed across multiple solid tumors.
Blend of Strategic Collaboration and In-House Approach to Manufacturing

Integral to the delivery of 2seventy bio’s platform of cell therapies is the company’s manufacturing network, including best-in-class partnerships with academic centers and industry, purpose-built for messenger RNA (mRNA) and lentiviral vector (LVV) production. This network also includes a planned build for an internal clinical cell therapy manufacturing capability at the company’s headquarters in Cambridge, Massachusetts. This facility is designed to enable deep integration of Chemistry, Manufacturing and Controls (CMC) with research, correlative science, and clinical development, and enable the flexibility to rapidly innovate and learn as programs advance.

Launching with a Strong Financial Foundation and Leadership

2seventy bio is launching with a clear and differentiated strategy and is well-funded to deliver:

ABECMA – In 3Q21, BMS reported total U.S. revenues of $67 million for ABECMA. 2seventy bio will continue to share equally in the costs and revenue for ABECMA in the U.S. The companies continue to experience robust demand for ABECMA and are working to improve manufacturing capacity and supply.
Board – 2seventy bio is launching with an experienced leadership team and Board of Directors, including:
Daniel S. Lynch (chairman – independent), Sarah Glickman (Audit Committee chair – Criteo), Denice Torres, J.D. (formerly of Johnson & Johnson), Ramy Ibrahim, M.D. (Broad Institute of MIT and Harvard), Marcela Maus, Ph.D. (Mass General Cancer Center), William Sellers, M.D. (Core Institute Member, Broad Institute of MIT, and Harvard) and Nick Leschly (2seventy bio)
Financial Position – 2seventy bio is launching with approximately $442 million in cash, which the company anticipates is sufficient to fund operations into 2023.