On November 12, 2021 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported results from an immunologic analysis of Phase 2 study data showing that trilaciclib enhances both CD4 and CD8 T cell function in certain patients with metastatic triple negative breast cancer (mTNBC) when administered prior to chemotherapy (Press release, G1 Therapeutics, NOV 12, 2021, View Source [SID1234595337]). Patients receiving placebo prior to chemotherapy did not demonstrate enhanced T cell function . Results of the immunologic analysis are being presented in a poster session at the 36th Annual Meeting of The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), Nov. 10-14, 2021. The poster is available in the scientific publications section of the G1’s website.

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"The Phase 2 immunologic data analysis suggests that administering trilaciclib prior to chemotherapy may enhance antitumor efficacy by modulating the composition and response of immune cell subsets," said John Yi, PhD, Director of Translational Medicine at G1 Therapeutics.

In the exploratory analysis, researchers sought to investigate the immune mechanisms underlying the improved rate of overall survival shown in the 2020 Phase 2 trial of TNBC patients receiving trilaciclib in combination with gemcitabine/carboplatin (GCb) compared with GCb alone. The researchers evaluated tumor samples and peripheral blood samples from patients at baseline and after trilaciclib/GCb administration or after placebo/GCb administration to identify differential gene expression and changes in immune function between the two groups. Further, they measured qualitative and quantitative differences between patients who did respond or did not respond to trilaciclib plus GCb. Response to treatment was defined as partial or complete response, while nonresponse was defined as stable or progressive disease.

Among the findings in the poster titled, "Immune Profiling to Investigate Improved Survival in Patients with Metastatic Triple-Negative Breast Cancer Receiving Trilaciclib Prior to Chemotherapy":

Patients who received trilaciclib prior to GCb showed increased T cell function as measured by greater production of inflammatory cytokines
Patients who received trilaciclib had fewer immune suppressing cells known as myeloid-derived suppressor cells (MDSCs) than patients who received GCb alone, whether they were responders or non-responders to treatment
Non-responders to trilaciclib/GCb had a reduction in circulating CD4 and CD8 T cells and a decreased production of inflammatory cytokines
"It is critical that we fully understand the underlying immune mechanisms that contributed to the overall survival improvement that was seen in the Phase 2 mTNBC trials, and to identify biomarkers that will clearly distinguish between trilaciclib responders and non-responders," said Dr. Yi. "We are further investigating the impact of trilaciclib on changes to the tumor-infiltrating immune response in our Phase 3 PRESERVE 2 trial in patients with mTNBC and in a planned mechanism-of-action trial in the neoadjuvant TNBC setting."

About Triple Negative Breast Cancer (TNBC)
According to the American Cancer Society, nearly 300,000 new cases of invasive breast cancer are diagnosed annually in the U.S. Triple-negative breast cancer makes up approximately 15% to 20% of such diagnosed breast cancers. TNBC is cancer that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein. Because TNBC cells lack key growth-signaling receptors, patients do not respond well to medications that block estrogen, progesterone, or HER2 receptors. Instead, treating TNBC typically involves chemotherapy, radiation, and surgery. TNBC is considered to be more aggressive and have a poorer prognosis than other types of breast cancer. In general, survival rates tend to be lower with TNBC compared to other forms of breast cancer, and TNBC is also more likely than some other types of breast cancer to return after it has been treated, especially in the first few years after treatment. It also tends to be higher grade than other types of breast cancer.

On November 12, 2021 Geron Corporation (Nasdaq: GERN), a late-stage biopharmaceutical company focused on the development and commercialization of treatments for hematologic malignancies, reported that John A. Scarlett, M.D., Geron’s Chairman and Chief Executive Officer, will present a company overview at the Stifel 2021 Virtual Healthcare Conference on Tuesday, November 16, 2021 at 2:40 p.m. ET (Press release, Geron, NOV 12, 2021, View Source [SID1234595393]).

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A live webcast of the presentation will be available through the Investor Relations section of Geron’s website under Events. Following the presentation, the webcast will be archived and available for replay for a period of 30 days.

On November 12, 2021 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on developing novel cancer immunotherapies for a broad range of indications, reported its financial results for the quarter ended September 30, 2021 and provided a business update (Press release, Sellas Life Sciences, NOV 12, 2021, View Source [SID1234595409]).

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"During the third quarter of 2021, in addition to continuing to enroll patients in the United States and Europe for our Phase 3 REGAL study of galinpepimut-S (GPS) in acute myeloid leukemia (AML) patients, we also commenced clinical and regulatory preparations for a potential new Phase 2/3 study of GPS in AML patients following a bone marrow transplant (BMT) who harbor minimal residual disease (MRD)," said Angelos M. Stergiou, MD, ScD. h.c., President and Chief Executive Officer of SELLAS. "We are excited to begin exploring GPS as a treatment option for this post-BMT population which, based on the retrospective outcomes data published earlier in the summer, remains an area of unmet need. We believe there is significant opportunity for GPS to become the key antileukemic vaccine immunotherapy in various AML settings, with the potential to treat patients who have undergone a BMT as well as patients who have achieved second remission in AML (CR2), the indication of our REGAL study."

Dr. Yair Levy, Director of Hematologic Malignancies at the Baylor University Medical Center, stated "I look forward to a clinical trial in transplanted patients that would address the high relapse rate among MRD positive (MRD+) AML patients. Although BMT remains the only truly curative treatment for AML patients with any significant disease risk, its benefit is limited by relapses in about 50% of patients who enter transplant with MRD. The trial being planned by SELLAS would explore whether GPS could be a treatment option for a much larger population of AML patients – i.e., those patients who have undergone BMT whose chances of remaining in remission could significantly improve as well as the large number of MRD+ patients who have been shown to have a high relapse rate after BMT or who do not undergo a BMT because they are considered unlikely to benefit from it."

Pipeline Update and Corporate Highlights:

Phase 3 REGAL Study:
Additional sites in the United States and European Union were activated during the third quarter with enrollment continuing. In addition, regulatory approval to commence the REGAL study was received in both Hungary and Taiwan during the quarter.
The final statistical analysis plan (SAP) for the REGAL study provides for a planned interim safety and futility analysis after 80 events (deaths) which the Company had anticipated would take place in the first half of 2022, provided that the ongoing COVID-19 pandemic did not significantly adversely impact our projected timeline for enrollment. Over the last 12 to 18 months, the Company has monitored the impact of the COVID-19 pandemic on the projected timeline for the REGAL study. During this period, the Company took several steps to mitigate possible and actual delays due to the COVID-19 pandemic, including increasing the number of clinical sites and the number of countries in which sites are located in order to maintain the original timeline. Despite these mitigation steps, the Company now anticipates that the interim analysis will take place in the second half of 2022, provided that the ongoing COVID-19 pandemic does not continue to adversely impact the projected timeline for enrollment. In addition to the planned interim analysis under the SAP, the final charter for the Independent Data Monitoring Committee for the REGAL study provides for enrollment-based safety, futility, and efficacy analyses prior to the planned interim analysis.

Planning for Potential Phase 2/3 GPS Study in AML Post-Transplant Patients: In August 2021, SELLAS hosted a Virtual Investor Symposium which focused on the potential for GPS in AML patients following a BMT. SELLAS management, Dr. Stergiou and Dr. Dragan Cicic, SVP, Clinical Development, were joined by leading cancer researcher Dr. Yair Levy, Director of Hematologic Malignancies at the Baylor University Medical Center. To access the event replay, click here. The Company is currently in the regulatory and clinical planning stages for a potential Phase 2/3 clinical trial of GPS in this patient population.

Red Door Community Award: On November 11, 2021, Angelos M. Stergiou, MD, ScD. h.c., President and Chief Executive Officer of SELLAS, was honored on behalf of SELLAS by the Red Door Community (formerly Gilda’s Club) with the Red Door Award for Advances in Research.
Financial Results for the Third Quarter 2021:

Licensing revenue: There was no licensing revenue for the third quarter of 2021 and $7.6 million for the nine months ended September 30, 2021, which consists of the recognition of revenue from the Company’s license agreement with 3D Medicines. The Company did not record any licensing revenue for the first nine months of 2020.

R&D Expenses: Research and development expenses for the third quarter of 2021 were $4.5 million, as compared to $2.4 million for the same period in 2020. Research and development expenses for the nine months ended September 30, 2021 were $12.3 million as compared to $6.5 million for the same period in 2020. The increase was primarily due to an increase in clinical trial expenses related to the Company’s Phase 3 REGAL clinical trial of GPS in AML patients and a ramp up of the manufacture of clinical trial materials and registration batches of GPS, a technology transfer to a new contract manufacturer, clinical drug supply purchase costs in the European Union in preparation for opening sites and enrolling patients in EU countries, and personnel related expenses due to increased headcount.

G&A Expenses: General and administrative expenses for the third quarter of 2021 were $2.4 million, as compared to $2.1 million for the same period in 2020. General and administrative expenses for the nine months ended September 30, 2021 were $8.8 million, as compared to $6.3 million for the same period in 2020. The increase was primarily due to amortization expense associated with the capitalized contract acquisition costs of the 3D Medicines license agreement, an increase in legal fees as compared to the same period in 2020 during which the majority of legal expenses were offset by a reimbursement credit, and personnel related expenses due to increased headcount.

Net Loss: Net loss attributable to common stockholders was $7.1 million for the third quarter of 2021, or a basic and diluted loss per share attributable to common stockholders of $0.45, as compared to a net loss attributable to common stockholders of $4.5 million for the same period in 2020, or a basic and diluted loss per share attributable to common stockholders of $0.53. Net loss attributable to common stockholders was $14.1 million for the nine months ended September 30, 2021, or a basic and diluted loss per share attributable to common stockholders of $0.92, as compared to a net loss attributable to common stockholders of $13.1 million for the same period in 2020, or a basic and diluted loss per share attributable to common stockholders of $1.83.

Cash Position: As of September 30, 2021, cash and cash equivalents totaled approximately $26.3 million.

On November 12, 2021 Neoleukin Therapeutics, Inc., "Neoleukin" (NASDAQ:NLTX), a biopharmaceutical company utilizing sophisticated computational methods to design de novo protein therapeutics, reported the presentation of new preclinical data on NL-201, an alpha-independent, de novo-designed IL-2 and IL-15 dual agonist, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 36TH Annual Meeting (SITC 2021) (Press release, Neoleukin Therapeutics, NOV 12, 2021, View Source [SID1234595447]).

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The presentation highlights preclinical data on NL-201 alone and in several combination regimens. NL-201 is a de novo 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 IL-2 receptor alpha subunit (CD25).

"The SITC (Free SITC Whitepaper) presentations highlight the broad potential of NL-201, which we believe to be the first fully de novo designed protein to enter clinical trials, to activate the immune system to fight cancer," said Jonathan Drachman, M.D., Chief Executive Officer of Neoleukin. "New data demonstrate that NL-201 can activate the tumor microenvironment and increase T-cell receptor diversity. We also found that local, intratumoral administration can control both the injected and distant tumors with improved tolerability compared to systemic administration in pre-clinical models. We are pleased to share this research as we continue to advance the NL-201 phase 1 clinical trial."

Further details from the presentations are as follows:

Poster/Abstract Number: 716
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

NL-201 turns "cold" tumors "hot" by increasing pro-inflammatory T cells and an immune signature in the tumor microenvironment and upregulating MHC-1 in tumors.
NL-201 stimulates pro-inflammatory tumor reprogramming without the coincident Treg expansion observed with PD-1 antibodies and other immuno-oncology agents.
NL-201 drives anti-tumor efficacy in a manner that is cooperative with PD-1 inhibition, including increasing TCR repertoire diversity.
Poster/Abstract Number: 898
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

Intratumoral NL-201 administration demonstrated:
Dose-dependent antitumor activity in syngeneic murine tumor models;_
Improved tolerability compared to systemic administration at equivalent dose levels and;
Durable tumor-specific immunity.
Results support clinical investigation of intratumoral NL-201 administration to increase NL-201 concentration in accessible lesions and reduce systemic exposure.
Poster/Abstract Number: 509
A First-in-Human Phase 1 Study of NL-201 in Patients with Relapsed or Refractory Cancer (Trials in Progress)

Assessing the safety profile and recommended Phase 2 dose and treatment schedule of NL-201.
Dose escalation and dose expansion cohorts.
Enrollment ongoing at multiple sites in North America and Australia.
Poster/Abstract Number: 563
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 g9d2 T Cell Activation and Proliferation

ICT01 plus NL-201 synergistically triggers gd T-cell activation, expansion and antitumor activity.
Data support clinical evaluation of this novel therapeutic approach.
The poster presentations are available on the Neoleukin website publications page: View Source

About NL-201
NL-201 is a de novo 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 low doses with minimal impact on immunosuppressive regulatory T cells. Furthermore, NL-201 has demonstrated both monotherapy and combination activity across a wide range of preclinical syngeneic tumor models.

On November 12, 2021 MiNA Therapeutics Limited ("MiNA" or the "Company"), the pioneer in small activating RNA (saRNA) therapeutics, reported that positive safety data from the Phase 1a/b TIMEPOINT study of MTL-CEBPA in combination with pembrolizumab in adult patients with advanced solid tumours (Press release, MiNA Therapeutics, NOV 12, 2021, View Source [SID1234595464]). The data will be initially presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, taking place on 10-14 November 2021. Separately, MiNA also highlights the publication of positive data in the peer-reviewed journal Clinical Cancer Research, demonstrating MTL-CEBPA’s mechanism of action across different tumour models and in cancer patients.

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Robert Habib, CEO of MiNA Therapeutics, commented:

"The data presented at SITC (Free SITC Whitepaper) and published in Clinical Cancer Research further adds to the strong foundation of clinical evidence we have established for MTL‑CEBPA. Multiple studies across different tumour models and in cancer patients have demonstrated the unique immunological effects of MTL-CEBPA and its role as a potential combination treatment in cancer. We are excited to progress into Phase 1b the development of MTL-CEBPA in patients with solid tumour malignancies."

Data presented at SITC (Free SITC Whitepaper) from the ongoing Phase 1a/b, first-in-human, open-label, multicenter TIMEPOINT study demonstrates the safety and tolerability of MiNA’s lead candidate, MTL-CEBPA in combination with pembrolizumab, an approved anti-PD-1 (programmed death receptor-1) checkpoint inhibitor. The study is enrolling patients with advanced solid tumour treatment settings in which anti-PD-1 checkpoint inhibitors are not approved therapies.

At the three dose levels tested, the combination was generally well tolerated, with no dose-limiting toxicity and no serious adverse events observed. Encouragingly, anti-tumour activity was also observed in three patients. These included two confirmed partial responses in patients with advanced ovarian cancer and malignant pleural mesothelioma. The data package to date supports the continuation of this programme and MiNA is currently enrolling patients into a Phase 1b dose expansion cohort, which will additionally assess immunological changes as well as clinical activity of the combination treatment. Analysis of approximately 40 patients in the Phase 1b dose expansion cohort is expected to complete in the second half of 2023.

Additionally, translational proof-of-concept data further establishing MTL-CEBPA’s mechanism of action was recently published in the peer-reviewed journal Clinical Cancer Research. The data demonstrated that therapeutic up-regulation of C/EBP-α by MTL-CEBPA caused inactivation of immune-suppressive myeloid cells, potentiating anti-tumour responses in patients with advanced primary liver cancer (hepatocellular carcinoma (HCC)), as well as in several pre-clinical tumor models, including liver cancer, lung carcinoma, and colon adenocarcinoma.

This data provides evidence to support the role of MTL-CEBPA to counteract a key cancer immune evasion pathway by inhibiting immune suppression by myeloid cells, and for the potential of MTL‑CEBPA in combination treatment with immunotherapies across multiple tumour types. This data also supports MiNA’s strategy in liver cancer, where the Company is investigating MTL-CEBPA in patients with advanced HCC in combination with sorafenib (standard-of-care multi-kinase inhibitor), with a randomised Phase 2 clinical trial (OUTREACH-2) expected to initiate around the end of 2021.

Both the poster presented at SITC (Free SITC Whitepaper) and paper published in Clinical Cancer Research will be made available on the Company’s website in the Publications section under "RNA Activation".

About the TIMEPOINT study

TIMEPOINT is a global Phase 1a/1b clinical study in patients with solid tumour malignancies that will assess the safety and tolerability of MTL‑CEBPA in combination with pembrolizumab in patients who are ineligible or resistant to standard therapies. The study has received clearance from the U.S. Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). To learn more about the TIMEPOINT clinical study, please visit our listing at clinicaltrials.gov.

About MTL-CEBPA

MTL-CEBPA is the first therapy that specifically up-regulates CCAAT/enhancer binding protein alpha (C/EBP-α), a transcription factor that acts as a master regulator of myeloid cell lineage determination and differentiation. Dysregulated myeloid cells have been implicated in several diseases and in solid tumour cancers have been identified as a critical barrier for many therapies to induce clinical responses. In pre-clinical studies MTL-CEBPA has been shown to improve the anti-tumour activity of cancer therapies by targeting dysregulated myeloid cells and reducing their suppressive effect in the tumour micro-environment. MTL-CEBPA is currently in clinical development as a combination therapy for the treatment of advanced liver cancer and advanced solid tumour malignancies.