On November 12, 2021 OncoHost, a global leader in next-generation precision oncology for improved personalized cancer therapy, reported that it has published a study identifying three distinct proteome subtypes that are associated with response from a cohort of non-small cell lung cancer (NSCLC) patients undergoing immunotherapy (Press release, OncoHost, NOV 12, 2021, View Source [SID1234595495]). The study was conducted using OncoHost’s first-of-its-kind, AI-based platform, PROphet, and its research and findings will be presented as an oral presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Anniversary Annual Meeting.

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Although the approval of immune checkpoint inhibitor (ICI)-based therapy has improved lung cancer outcomes, most patients still do not respond to treatment. Moreover, a growing body of evidence demonstrates that in some cases, the interplay between the treatment, tumor and host can lead to a counterintuitive effect, supporting tumor progression and spread. Understanding the biological processes that drive resistance to treatment is critical in order to improve clinical outcomes. This study seeks to take a deeper look into the host’s micro-environment to identify biomarkers for response to immunotherapy, as well as to gain insights into mechanisms of resistance to treatment and understand the resistance biology.

"By conducting plasma proteomic profiling and assessing multidimensional clinical and biological data, we have achieved success in analyzing, clustering and predicting response in NSCLC patients," said Professor Yuval Shaked, founder and Chief Scientific Advisor at OncoHost, and Professor of Cell Biology and Cancer Science at the Technion – Israel Institute of Technology. "This research is helping us take significant strides in understanding the biological processes that are driving resistance in patients, and we are honored to play a role in the evolution of cancer care."

The study included a cohort comprised of 143 patients from whom plasma samples were collected pre-treatment and in the early stages of treatment, along with comprehensive clinical data. Using PROphet, OncoHost’s advanced machine learning and bioinformatics platform, researchers divided the cohort into three patient clusters, each with distinct biological and clinical characteristics. While the patients in all three clusters may have had the same diagnosis, they all fit into just one of three proteome subtypes, which are associated with their treatment responsiveness.

"Painting a distinct proteome picture, this study has shown us that PROphet can predict response and analyze resistance for every patient, sub-grouping and differentiating them based on their resistance assessment," said Ofer Sharon, CEO of OncoHost. "In order to provide oncologists and patients with tangible, actionable clinical insights, it’s not enough to predict which patients will be more responsive to treatment; we should also understand the reason behind it. PROphet has allowed us to reach this deep level of resolution and insight."

The clinical study was conducted in collaboration with Sidney Kimmel Medical College at Thomas Jefferson University, The Ohio State University Wexner Medical Center, Sheba Medical Center, the Technion Institute of Technology and Tel Aviv University. The presentation will take place at SITC (Free SITC Whitepaper) on November 12, 2021, at 13:03 EST. This study will be published as a full peer-reviewed manuscript in 2022.

On November 12, 2021 Nektar Therapeutics (Nasdaq: NKTR) reported three data presentations for its I-O pipeline at the 2021 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, Nektar Therapeutics, NOV 12, 2021, View Source [SID1234595494]).

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Initial clinical results were presented from the dose-escalation stage of a Phase 1/2 study of NKTR-255 in combination with cetuximab in a late-breaking abstract presented by Mehmet Altan, MD, Assistant Professor, Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center on Friday, November 12th. Collaborator presentations of translational data for bempegaldesleukin in combination with nivolumab and bempegaldesleukin in combination with NKTR-262 data were also featured in two poster presentations by Arika S. Feils at the Department of Human Oncology, University of Wisconsin School of Medicine and Public Health and Annah Rolig, PhD, Earle A. Chiles Research Institute, Providence Cancer Institute, respectively, on Friday, November 12th.

"The data presented at this year’s SITC (Free SITC Whitepaper) meeting highlight the strength of our cytokine portfolio and in particular the potential of NKTR-255 in the treatment of patients with solid tumors," said Jonathan Zalevsky, Ph.D., Senior Vice President and Chief Research & Development Officer at Nektar. "We were excited to see early evidence of clinical benefit in the first patients treated in the dose-escalation portion of the study for NKTR-255 in combination with cetuximab which reinforces the promising synergy of IL-15 in combination with an antibody-dependent cellular cytotoxicity agent for the treatment of solid tumors."

2021 SITC (Free SITC Whitepaper) presentations are available for download at View Source

Highlights from the presentations are as follows:

Abstract 957: "NKTR-255 Plus Cetuximab in Patients with Solid Tumors: Interim Safety and Efficacy Results from the Phase 1b Dose Escalation Study", Altan, M., et al.

The combination of NKTR-255 + cetuximab was well tolerated at NKTR-255 doses of 1.5 and 3.0 μg/kg every three weeks (Q21D) and treatment-related adverse events were generally low-grade, transient, and easily managed.
Early evidence of on-target biological activity was observed with treatment with NKTR-255 leading to expansion and proliferation of Natural Killer (NK) cells and CD8+ T cells.
Early evidence of clinical activity was observed in 9 patients that were evaluable for efficacy [6 colorectal (CRC) patients, 3 squamous cell carcinoma of head and neck (SCCHN) patients] with 1 CRC patient achieving a confirmed partial response (PR) with 52% tumor reduction by RECIST and 5 patients experiencing stable disease (SD) by RECIST [3 CRC, 2 SCCHN] in this heavily pre-treated and highly refractory patient population. 8 of the 9 patients evaluable for efficacy had also received prior treatment with an EGFR-targeted therapy and/or a checkpoint inhibitor.
The maximum tolerated dose and recommended Phase 2 dose have not been reached yet and dose escalation of NKTR-255 + cetuximab is ongoing in patients with R/R SCCHN and CRC.
Abstract 59: "Associations between KIR/KIR-ligand genotypes and clinical outcome for patients with advanced solid tumors receiving BEMPEG plus nivolumab combination therapy in the PIVOT-02 trial", Feils, AS., et al.

Individuals who were positive for KIR2DL2 and its HLA-C1 ligand had significantly greater TS (p=0.01) and longer PFS (p=0.04) with a trend towards increased ORR (p=0.07).
No significant associations were found between an individual’s clinical outcome and their KIR3DL1 and HLA-Bw4 ligand status.
Individuals who were positive for both KIR2DL2 and KIR3DL1 with their HLA-C1 and HLA-Bw4 ligands, respectively, had significantly greater TS (p=0.04) and increased ORR with a trend towards longer PFS (p=0.07).
No significant associations were found between an individual’s clinical outcome and their KIR/KIR-ligand present versus missing status.
Abstract 596: "Combining Bempegaldesleukin (CD122-preferential IL-2 pathway agonist) and NKTR-262 (TLR7/8 agonist) pairs local innate activation with systemic CD8+ T cell expansion to enhance anti-tumor immunity", Rolig, A., et al.

BEMPEG+NKTR-262 preclinical efficacy is superior to BEMPEG+RT efficacy and relies on CD8+ T cells.
BEMPEG+NKTR-262 combination therapy produces a higher fraction of activated, tumor antigen-specific cytotoxic CD8+ T cells systemically, correlating with superior anti-tumor efficacy relative to BEMPEG+RT in preclinical models.
In preclinical models, BEMPEG+NKTR-262 therapy induces active (GzmA+, Ki-67+) AH1-A5-CD8+ T cell that are supported by type 1 IFN signaling, suggesting bystander T cell activity.
In preclinical models, BEMPEG+NKTR-262 combination therapy induces intratumoral CD8+ T cells that have increased activity as demonstrated by increased granzyme expression, increased cytolytic capacity, and reduced conversion to an exhausted phenotype (PD-1+).
Analyst Call with Cancer Specialist:

Nektar management will host an analyst and investor conference call to review the data presentation for NKTR-255 at SITC (Free SITC Whitepaper) 2021. The call will also include two invited speakers:

Mehmet Altan, MD, Assistant Professor, Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center
Alan Tan, MD, Director of GU Medical Oncology and Assistant Professor in the Division of Hematology, Oncology and Cell Therapy at Rush University Medical Center
Date and Time: Friday, November 12, 2021 at 12:00 p.m. EST

Dial-in: 877-881-2183 (toll-free) or 970-315-0453 (enter access code 1769208)

Investors and analysts can also view slides and listen to the live audio webcast of the presentation at View Source The event will also be available for replay for two weeks on the company’s website, www.nektar.com.

Biography for Mehmet Altan, MD

Mehmet Altan, MD, is an Assistant Professor in the Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. Dr. Altan is one of the lead investigators in the phase 1/2, dose-escalation and dose-expansion study of NKTR-255 in combination with cetuximab in patients with refractory 2nd and 3rd line metastatic colorectal cancer or metastatic head and neck cancer. His current research areas include identification of mechanisms for primary and secondary resistance to immunotherapies and predictive markers for immunotherapy toxicities. He also works on translational research projects for identification of spatiotemporal dynamics of the tumor microenvironment in response to immunotherapy to define potential therapeutic targets.

Biography for Alan Tan, MD

Alan Tan, MD, is an Assistant Professor in the Division of Hematology, Oncology and Cell Therapy at Rush Medical College. He specializes in kidney cancer, bladder cancer, prostate cancer and melanoma. He also has an extensive background in hematologic malignancies. Dr. Tan has clinical research interest in designing and implementing clinical trials to test novel immunotherapies and targeted therapies for renal cell carcinoma and GU malignancies. He also has interest in precision genomic cancer medicine, identifying molecular alterations that will serve as targets for individualized treatment strategies.

On November 12, 2021 Second Genome, a biotechnology company that leverages its proprietary platform sg-4sight to discover and develop precision therapies and biomarkers, reported that preclinical data demonstrating that the Company’s CXCR3-positive allosteric modulator, SG-3-00802, can reverse resistance to anti-programmed death protein-1 (PD-1) therapy, illustrating that the microbiome directly interacts with the human immune system to enhance immunity and impact antitumor activity (Press release, Second Genome, NOV 12, 2021, View Source [SID1234595493]). The data (E-Poster #569) were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting, held virtually and in Washington, D.C. November 10-14.

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"We are encouraged by Second Genome’s growing body of preclinical data demonstrating that SG-3-00802’s differentiated mechanism of action has the potential to effectively target the tumor microenvironment and improve responses in combination with existing immunotherapies, such as checkpoint inhibitors and cytokines," said Karim Dabbagh, Ph.D., Chief Executive Officer at Second Genome. "At SITC (Free SITC Whitepaper), we presented new data showing SG-3-00802 potently enhances CXCR3 ligand-induced cell migration, a critical effector cell recruitment mechanism for anti-tumor immunity. We look forward to further advancing our program with an IND submission expected in 2022."

The poster presentation will be available for on-demand viewing on the SITC (Free SITC Whitepaper) website through January 9, 2022, and it will also be made available on the Company’s website at View Source

On November 12, 2021 CASI Pharmaceuticals, Inc. (Nasdaq: CASI), is a U.S. biopharmaceutical company focused on developing and commercializing innovative therapeutics and pharmaceutical products, reported financial results for the third quarter of 2021 (Press release, CASI Pharmaceuticals, NOV 12, 2021, View Source [SID1234595492]).

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Wei-Wu He, Ph.D., CASI’s Chairman and Chief Executive Officer, commented, "We are pleased to report $8.1 million in EVOMELA revenues for the quarter. We remain confident in our guidance for our full-year 2021 revenue growth to exceed 2020 revenues by over 80%. This continued growth further demonstrates our 100+ person sales and marketing team’s ability to cover all major hospitals and key multiple myeloma transplant physicians. We look forward to leveraging this success in the anticipated launch of our next product, Juventas’ CNCT-19, which our partner announced has officially entered phase II of a registered clinical trial, and other products."

Dr. He continued, "Our partner BioInvent announced additional positive, interim top-line data from the Phase 1/2a clinical trial of its novel anti-FcγRIIB antibody BI-1206 in combination with rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with indolent relapsed or refractory B-cell non-Hodgkin’s lymphoma (NHL). BI-1206, in combination with rituximab, demonstrated an objective response rate (ORR) of 50%, with three complete responses and three partial responses seen in twelve patients evaluated for therapeutic benefit. The treatment stabilized the disease in one additional patient, giving a disease control rate of 58% (7 out of 12 patients). We believe BI-1206 has potential application across multiple tumor types in both first-line treatments and relapsed/refractory settings. Additionally, our CNCT-19 CAR-T partner, Juventas, completed a Series C financing round through which it raised more than RMB410 million (approximately $63 million USD). CASI has a 12.01% ownership stake in Juventas and shares global co-commercial and profit-sharing rights for CNCT-19 with Juventas. We believe this financing will allow Juventas to continue the rapid development and registration of CNCT-19 in China. Overall, we are pleased with our momentum and will continue to execute on key milestones across our broad portfolio in the quarters ahead."

Third Quarter 2021 Financial Results

Revenues consist of product sales of EVOMELA that launched during August 2019. Revenue was $8.1 million for the three months ended September 30, 2021 compared to $4.2 million for the three months ended September 30, 2020. Revenues increased by 93% in the third quarter of 2021 as compared to same quarter in 2020 due to the continued strong growth in EVOMELA sales.

Costs of revenues were $3.4 million for the three months ended September 30, 2021, compared to $1.8 million for the three months ended September 30, 2020, which includes royalty payment of $1.6 million and $0.8 million for the same period. Costs of revenues excluding royalty were $1.8 million and $1.0 million for the three months ended September 30, 2021, and 2020. Costs of revenues, excluding royalty as a percentage of revenues, decreased significantly in the three months ended September 30, 2021, compared within the three months ended September 30, 2020, due to the alternate manufacturer in place, resulting in a considerable decrease in the unit cost of inventories of EVOMELA.

General and administrative expenses for the three months ended September 30, 2021 were $5.3 million, compared with $5.3 million for the three months ended September 30, 2020.

Selling and marketing expenses for the three months ended September 30, 2021 were $3.4 million, compared with $2.1 million for the three months ended September 30, 2020. The increase in selling and marketing expenses was due to expansion of sales team in China in 2021.

R&D expenses for the three months ended September 30, 2021 were $2.9 million, compared to $2.8 million for the three months ended September 30, 2020.

Net loss for the three months ended September 30, 2021 was $10 million compared to $16.7 million for the three months ended September 30, 2020 due to the increase in revenues. As of September 30, 2021, CASI had cash and cash equivalents of $53.1 million compared to $57.1 million as of December 31, 2020.
Further information regarding the Company, including its Quarterly Report on Form 10-Q for the quarter ended June 30, 2021, can be found at www.casipharmaceuticals.com.

Conference Call

The conference call can be accessed by dialing 1-877-870-4263 (U.S.) or 1-412-317-0790 (international) and ask to be joined into the CASI Pharmaceuticals call to listen to the live conference call.

This call will be recorded and available for replay by dialing 1-877-344-7529 (U.S.) or 1-412-317-0088 (international) and enter 10160251 to access the replay.

On November 12, 2021 Grey Wolf Therapeutics, a biotechnology company spearheading a new therapeutic approach to immuno-oncology driven by targeted neoantigen generation, reported the presentation of promising preclinical in vivo data on the company’s first-in-class inhibitors of ERAP1 at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Grey Wolf Therapeutics, NOV 12, 2021, View Source [SID1234595491]). The results are featured in a poster presentation (#553) entitled, "First-in-Class Inhibitors of ERAP1 Alter the Immunopeptidome of Cancer, Driving a Differentiated T Cell Response Leading to Tumor Growth Inhibition," at the SITC (Free SITC Whitepaper) conference, being held November 10-14, 2021 in Washington, D.C., as well as virtually.

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Grey Wolf Therapeutics’ first-of-its-kind immuno-oncology approach is centered on dramatically increasing the visibility of tumors to allow for their identification and destruction by the body’s immune system. This is achieved through targeted inhibition of the endoplasmic reticulum aminopeptidases (ERAP1 and ERAP2), causing the generation and presentation of novel and potent neoantigens to the surface of tumor cells. The appearance of these neoantigens uncloaks the tumor cells, illuminating them for the immune system and setting in motion powerful, differentiated T cell responses against the tumor. Importantly, this unique approach is orthogonal to a broad range of other cancer therapy modalities, including, but not limited to, immunotherapy.

The presented findings at the SITC (Free SITC Whitepaper) conference provide compelling evidence for several key elements of the company’s therapeutic hypothesis for ERAP1 inhibition in the treatment of cancer. These include the ability of the company’s ERAP1 inhibitors to drive neoantigen creation, differentiated T cell responses, and tumor growth inhibition.

Key highlights from the company’s presentation include:

Neoantigen Creation

Researchers highlighted study results demonstrating that ERAP1 inhibition triggered clear generation of novel neoantigens, as well as increased expression of existing neoantigens, across various species, cell types and genetic backgrounds in vitro and in vivo. For example, targeted ERAP1 inhibition within the HCT116 colorectal cancer cell line led to increased surface expression of key cancer antigens including MAGE3 and PBK, as well as the generation of an entirely new neoantigen (ATAD2) within the tumor. This neoantigen generation is believed to make the tumor significantly more visible to the immune system, allowing for the desired differentiated T cell response.

Differentiated T Cell Response

Presented findings highlighted three different data sets supporting the ability of ERAP1 inhibition to drive a differentiated T cell response.

First, results demonstrated a statistically significant increase in T cell receptor (TCR) diversity across a range of timepoints following treatment with an ERAP1 inhibitor and an anti-PD-1 antibody in the CT26 tumor model. Second, data demonstrated that the combination of an ERAP1 inhibitor and anti-PD-1 in the CT26 model drove a significant increase in T cell infiltration into the tumor in conjunction with elevated intra-tumoral Granzyme. Finally, the treatment combination led to a significant elevation of a broad range of translationally relevant immune markers that have been shown to correlate with patient response to anti-PD-1 treatment, including CXCL9, CXCL10, IFNg and IL-7R.

It is important to note that this impact on immune markers is tumor-specific as it was only observed within tumors and not in the periphery, suggesting that ERAP1 inhibition is driving an entirely novel, cancer-specific response.

Tumor Growth Inhibition

The ability of ERAP1 inhibition to drive neoantigen creation and the subsequent differentiated T cell response resulted in a meaningful impact on tumor growth. Presented study results demonstrated clear tumor growth inhibition and improved overall survival in multiple syngeneic mouse models following treatment with ERAP1 inhibitors in combination with an anti-PD-1 antibody, as compared to vehicle. Significantly, in the CT26 syngeneic mouse model, each of the findings demonstrating a differentiated T cell response (i.e., TCR repertoire changes, T cell infiltration and upregulation of translationally relevant immune markers) correlates with tumor growth inhibition providing compelling evidence for neoantigen creation driving anti-tumor responses.

"The totality of these presented data provides compelling support for our belief that the generation of novel neoantigens through targeted inhibition of ERAP1 represents a promising, entirely new approach to the oncology drug development space. While we have previously shown the potential of our ERAP1 inhibitors to generate neoantigens that drive anti-tumor responses, these new data presented today clearly demonstrate that the anti-tumor responses are due to a novel and differentiated T cell response," said Peter Joyce, Ph.D., chief executive officer of Grey Wolf Therapeutics. "While these promising results were achieved by combining our ERAP1 inhibitors with an anti-PD-1 antibody, it is important to note that we believe our unique approach will be orthogonal to a broad range of other cancer therapy modalities, including, but not limited to, immunotherapy. Based on these data, we continue to progress our lead ERAP1 inhibitor drug candidate through preclinical development, with the goal of advancing into the clinic in the second half of 2022."

Grey Wolf Therapeutics is developing a portfolio of ERAP inhibitors that it believes represents the first ever application of direct neoantigen generation to the treatment of cancer. GRWD5769, the company’s lead ERAP1 inhibitor development candidate, is expected to enter the clinic in the second half of 2022.