On November 12, 2021 Silverback Therapeutics, Inc. (Nasdaq: SBTX) ("Silverback"), a clinical-stage biopharmaceutical company leveraging its proprietary ImmunoTAC technology platform to develop systemically delivered, tissue targeted therapeutics for the treatment of cancer, chronic viral infections, and other serious diseases, reported a trial-in-progress poster on SBT6050-201 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting, held virtually from November 10-14, 2021 (Press release, Silverback Therapeutics, NOV 12, 2021, View Source [SID1234595411]). SBT6050-201 is a Phase 1/2 study evaluating SBT6050 in combination with trastuzumab deruxtecan (Enhertu), or with trastuzumab (Herceptin) and tucatinib (Tukysa) with or without capecitabine, in patients with HER2-expressing or HER2-amplified gastroesophageal, non-small cell lung, breast, and colorectal cancers.

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"SBT6050 was designed to enable combinations with trastuzumab-containing regimens, which are foundational in the standard of care for HER2-positive solid tumors," said Naomi Hunder, M.D., chief medical officer of Silverback Therapeutics. "There is compelling scientific and clinical rationale to combine SBT6050 with these regimens. Importantly, in addition to the trastuzumab component of these regimens, they each contain a cytotoxic component that drives immunogenic cell death, releasing tumor neoantigens. SBT6050 activates dendritic cells, potentially enhancing neoantigen presentation to T cells and amplifying the anti-tumor response. SBT6050 may also enhance trastuzumab-mediated antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. We look forward to initiating clinical evaluation of these combinations in the first quarter of 2022."

The poster is now available on the SITC (Free SITC Whitepaper) website and on the Silverback website here. Details are as follows:

Poster Title: A phase 1/2 study of SBT6050 combined with trastuzumab deruxtecan (T-DXd) or trastuzumab and tucatinib with or without capecitabine in patients with HER2-expressing or HER2-amplified cancers
Presenter: Sam J. Klempner, MD
Category: Clinical Trials in Progress
Abstract Number: 393

About SBT6050

SBT6050 is the first of a new class of targeted immuno-oncology agents designed to direct a TLR8 agonist linker-payload to activate myeloid cells in tumors expressing moderate to high levels of HER2. TLR8 is expressed in myeloid cell types prevalent in human tumors and TLR8 agonism can activate a broad spectrum of anti-tumor immune mechanisms, including pathways involved in the innate and adaptive immune response. SBT6050 was specifically designed to bind to the HER2 sub-domain II, the pertuzumab epitope, to enable combinations with trastuzumab-containing therapies. SBT6050 is currently being evaluated in a Phase 1/1b trial in patients with advanced or metastatic HER2-expressing or amplified solid tumors.

On November 12, 2021 Sensei Biotherapeutics, Inc. (NASDAQ: SNSE), an immunotherapy company focused on the discovery and development of next generation therapeutics for cancer, reported the first preclinical data for SNS-101, its anti-VISTA (V-domain Ig suppressor of T cell activation) product candidate (Press release, Sensei Biotherapeutics, NOV 12, 2021, View Source [SID1234595410]). The data will be presented during a poster session on November 13, 2021, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC 2021) 36th Annual Meeting in Washington, D.C. and virtually .

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"VISTA has been recognized for years as an important immune checkpoint but has been difficult to drug due to its unique pH-dependent biology," said Robert Pierce, M.D. chief scientific officer of Sensei Biotherapeutics. "VISTA is primarily expressed on myeloid cells, a hub of immunosuppressive activity, and functions as a checkpoint exclusively under acidic conditions where it binds to its receptor, PSGL-1. Our scientific team has been evaluating VISTA for several years. Accordingly, we believe, the key to unlocking the power of this checkpoint lies with the development of an antibody that selectively binds the active form of VISTA that is only present within the low pH of the tumor microenvironment. At SITC (Free SITC Whitepaper), we are excited to share the preclinical data demonstrating that SNS-101 binds active VISTA with high affinity and significant selectivity (~600-fold increase at pH 6.0 versus 7.4)."

Dr. Pierce continued, "We are also encouraged by early in vivo evidence from a human VISTA knock-in mouse model showing improved immune responses, including the anticipated combination effect with anti-PD1 in a PD1 blockade responsive tumor model. We continue to expand on this research and are looking forward to sharing more in vivo data at a future medical conference. IND-enabling studies are already underway to evaluate the potential of SNS-101 to become a novel treatment for solid cancers, as both a monotherapy and in combination, that overcomes on-target/off-tumor toxicities seen today with other I/O approaches."

Preclinical data for SNS-101 are being presented in a poster (#228) titled: "Antagonistic pH-selective VISTA antibody SNS-101 potentiates anti-PD-1/PD-L1-induced anti-tumor immunity." A summary of data in the poster include:

Preclinical data demonstrated that SNS-101 successfully blocked the interaction of VISTA with its PSGL-1 receptor, demonstrating high-affinity binding to low pH-VISTA sub-nanomolar affinity with exemplary (>600-fold) pH-selectivity vs. physiologic pH-VISTA.
SNS-101, in combination with an anti-PD-1 inhibitor, led to superior anti-tumor activity compared to PD-1 alone.
SNS-101 is a fully human IgG1 and has entered IND-enabling studies.
Sensei will host a virtual science symposium on Tuesday, November 16, 2021, at 4:00 p.m. Eastern Time to discuss the potential of the VISTA checkpoint inhibitor to address current limitations of immune checkpoint therapy. The event will be hosted by Sensei’s management team and will include a presentation on VISTA biology by Robert Schreiber, Ph.D., the Andrew M. Bursky and Jane M. Bursky Distinguished Professor of Pathology and Immunology, Professor of Molecular Microbiology and co-leader of the tumor immunology program at the Siteman Comprehensive Cancer Center and Founding Director of the Center for Human Immunology and Immunotherapy Programs at the Washington University School of Medicine.

A live webcast of the symposium will be available under "Events & Presentations" in the Investors section of the company’s website at www.senseibio.com. An archived replay will be available for approximately 90 days following the event.

About VISTA (V-domain Ig suppressor of T cell activation)

VISTA (B7-H5) is recognized as an important immune checkpoint regulator that is expressed primarily on myeloid cells, a hub of immunosuppressive activity, and acts via binding to its receptor on T-cells (PSGL-1) at sub physiologic pH. Disrupting the interaction of VISTA and its receptor on T-cells has been shown to enhance T-cell activation and tumor cell death. The VISTA-PSGL-1 T-cell checkpoint is activated under low pH conditions such as the tumor microenvironment. VISTA is found to be expressed in numerous cancer types and appears to be associated with PD-1 resistance.

The therapeutic hypothesis that Sensei believes differentiates its VISTA program is that an effective and safe inhibitory anti-VISTA antibody must demonstrate: (1) selective binding to the active form of VISTA (protonated/low pH) in order to avoid target mediated drug disposition and on-target/off-tumor effects; (2) effective inhibition of active VISTA’s interaction with PSGL-1; and (3) Fc-mediated activation of tumor resident myeloid cells to facilitate conversion from an immunosuppressive to an immune-activating phenotype.

About SNS-101
SNS-101 is a potent, pH-dependent fully human monoclonal antibody designed to block the interaction of VISTA, a novel immune checkpoint that is expressed primarily on myeloid cells, with its receptor, PSGL-1. Selectivity is achieved because SNS-101 targets the active (i.e., protonated) VISTA present in the low pH tumor microenvironment. SNS-101 was selected based on 1) the lack of significant binding to VISTA at physiologic pH (i.e., deprotonated VISTA in the blood), and 2) its high-affinity binding to active VISTA (pH 6.0), which yielded a > 600-fold selectivity. Based on the biochemical properties of SNS-101, Sensei anticipates tumor microenvironment selective activity for this preclinical product candidate. VISTA has been shown to be expressed in numerous tumor types, including non-small cell lung cancer (NSCLC).

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 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 for the treatment of cancer and autoimmune diseases, reported the poster presentation of preclinical data for RTX-224, a broad immune costimulatory agonist for the treatment of cancer, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting which is being held from November 10-14, 2021, in Washington, D.C., and virtually (Press release, Rubius Therapeutics, NOV 12, 2021, View Source [SID1234595408]).

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"The preclinical data presented at SITC (Free SITC Whitepaper) indicate that RTX-224 stimulates both adaptive and innate immune responses, leading to an antitumor effect in our surrogate models," said Laurence Turka, M.D., chief scientific officer and head of research & translational medicine of Rubius Therapeutics. "Our preclinical model of RTX-224 demonstrated significant activation of CD4+ T cells, CD8+ T cells, antigen-presenting cells and NK cells as well as potent anti-tumor activity in a melanoma model, giving us confidence that RTX-224 may be an effective treatment for advanced solid tumors. The U.S. FDA recently cleared our Investigational New Drug application for RTX-224, and we expect to begin dosing patients during the first quarter of 2022."

Poster Title: RTX-224, An Engineered Allogeneic Red Cell Therapeutic Expressing 4-1BBL and IL-12, Activates Immune Cells in Blood and Spleen to Promote Tumor Growth Inhibition in Mice

RTX-224 is an allogeneic cellular therapy product candidate that is engineered to express hundreds of thousands of copies of 4-1BB ligand (4-1BBL) and interleukin-12 (IL-12) on the cell surface. RTX-224 is designed as a broad immune agonist of both adaptive and innate responses, activating CD8+ and CD4+ T cells, promoting antigen presentation and activating and expanding NK cells. It is expected to produce a broad and potent anti-tumor T cell response, an innate immune response and have anti-tumor activity in those tumor types with known sensitivity to T cell killing, including tumor types with high mutational burden, PD-L1 expression and prior responsiveness to checkpoint inhibitors.

Data Summary

The mouse surrogate of RTX-224, mRBC-224, demonstrated potent anti-tumor activity in B16F10 melanoma models, intravenously and subcutaneously, that was associated with pharmacodynamic changes in the tumors, including activated CD8+ T cells, NK cells and macrophages.
mRBC-224 distributed mainly in the spleen of tumor-bearing mice 24 hours after one dose.
mRBC-224 treatment in mice promoted activation of NK cells, CD8+ T cells and monocytes/macrophages in the blood and spleen of naïve and tumor-bearing mice.
RTX‑224 (in vitro) and mRBC‑224 (in vivo) stimulate adaptive (CD8+ T cells and CD4+ T cells) and innate (NK cells and macrophages) immune responses.
The combined enhancement of both adaptive and innate immune responses leads to a productive antitumor response as demonstrated in preclinical studies.

On November 21, 2021 Replimune Group, Inc. (Nasdaq: REPL), a biotechnology company developing oncolytic immuno-gene therapies derived from its Immulytic platform, reported updated interim data from the Phase 1 data from RP2 alone and in combination with Opdivo that continues to provide strong support for the next stage development of RP2 (Press release, Replimune, NOV 12, 2021, View Source [SID1234595407]). The poster will be presented November 12-14, 2021 at 7:00 a.m. ET to 5:00 p.m. ET at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting being held November 10-14, 2021.

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Updated RP2 data shows compelling durability of response as single agent and in combination with Opdivo providing additional evidence of the clinical utility of RP2 in patients with hard-to-treat, anti-PD1 failed cancers.

RP2 leverages Replimune’s platform to express an anti-CTLA-4 antibody, in addition to GALV-GP R- and GM-CSF which is expressed by RP1. The Company has now fully enrolled the 30-patient cohort evaluating RP2 combined with Opdivo following previously completing enrolment of the 9-patient cohort evaluating RP2 as monotherapy. The Phase 1 clinical trial population comprised patients with advanced cancers having failed, or being ineligible for, standard of care options.

The updated interim data shows:

In the nine-patient monotherapy cohort with RP2, two of the initial three patients who achieved response remain in response, these being a patient with esophageal cancer (partial response; previously anti-PDL1 failed) at 22 months from entering the trial and a patient with mucoepidermoid carcinoma (complete response) at 19 months from entering the trial. As previously reported, the third responding patient with uveal melanoma with a partial response (Yervoy/Opdivo failed) progressed at 15 months from entering the trial.
Updated data from the 30-patient cohort of RP2 in combination with Opdivo shows durable responses ongoing at out to >425 days.
To date, seven of the 30 patient (23.3%) cohort of RP2 in combination with Opdivo have achieved partial responses, with additional patients still on study with the opportunity to achieve a response. Six of the seven responses are ongoing with depth of response having been maintained or deepened over time.
The responding patients are four of nine patients with cutaneous melanoma (all anti-PD1 or anti-PD1 and anti-CTLA-4 failed), two of eight patients with uveal melanoma (anti-PD1 or anti-PD1 and anti-CTLA-4 failed) and one of three patients with squamous cell carcinoma of the head and neck (anti-PD1 failed).
Biomarker data continues to demonstrate substantial increases CD8 T cells and PD-L1 expression, with T cell receptor sequencing and Nanostring expression analysis further indicating potent and broad activation of an anti-tumor immune response.
No correlation has been observed between the degree of anti-tumor response and the baseline levels of PD-L1 expression, in line with the intended mechanism of action for RP2 of turning immunologically ‘cold’ tumors ‘hot’.
Overall the data, including the durability of the responses, continues to support that oncolytic immunotherapy-mediated expression of anti-CTLA-4 from RP2 provides potent & systemic anti-tumor effects, without substantial additional toxicity as compared to the oncolytic backbone (RP1), including without evidence of the side effects associated with systemic ipilimumab.
Based on the observation of durable clinical responses in patients with liver metastases following treatment with both RP1 and RP2, the Company has amended the clinical trial protocol to enrol an additional 24 patients with liver metastases from lung cancer, gastrointestinal cancers, breast cancer and uveal melanoma.
Replimune will also be presenting three additional Trial in Progress presentations at this year’s SITC (Free SITC Whitepaper) Annual Meeting

Abstract Title: ARTACUS: An open-label, multicenter, phase 1b/2 study of RP1 in solid organ transplant recipients with advanced cutaneous malignancies (Trial in Progress presentation)
Abstract Number: 550
Session Date and Time: November 12-14, 2021 from 7:00 AM ET- 5:00 PM ET
Location: Hall E

Abstract Title: CERPASS: A randomized, controlled, open-label, phase 2 study of cemiplimab ± RP1 in patients with advanced cutaneous squamous cell carcinoma (Trial in Progress presentation)
Abstract Number: 547
Session Date and Time: November 12-14, 2021 from 7:00 AM ET- 5:00 PM ET
Location: Hall E

Abstract Title: IGNYTE: An open-label, multicenter, phase 1/2 (Ph 1/2) clinical trial of RP1 ± nivolumab in patients with advanced solid tumors (Trial in Progress presentation)
Abstract Number: 506
Session Date and Time: November 12-14, 2021 from 7:00 AM ET- 5:00 PM ET
Location: Hall E

The full posters will be posted to the presentations section of the Replimune website at View Source