On November 12, 2021 Elicio Therapeutics, a clinical-stage biotechnology company developing a pipeline of novel immunotherapies for the treatment of cancer and other diseases, reported two ePoster presentations of preclinical data on its Amphiphile (AMP) platform in combination with TCR-T and CAR-T therapies, respectively, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting taking place in Washington D.C. and virtually November 10-14, 2021 (Press release, Elicio Therapeutics, NOV 12, 2021, https://elicio.com/2021/11/elicio-therapeutics-presents-preclinical-data-on-amp-tcr-t-and-car-t-combination-therapies-at-the-2021-society-for-immunotherapy-of-cancer-annual-meeting/ [SID1234595391]). The ePosters are available on the SITC (Free SITC Whitepaper) website starting November 12, 2021, at 7 a.m. ET., and accessible here.

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"These preclinical datasets demonstrate the broad potential of our AMP platform and build on previous data validating our AMP boosting approach to enhance already established TCR-T and CAR-T cell therapies. By successfully targeting the lymph nodes, AMP-boosting can enhance both adoptively transferred and endogenous T cell responses to activate potent, functional and durable immunity against tumors," said Peter DeMuth, Ph.D., Vice President of Research at Elicio Therapeutics. "We are excited to continue building on these data to enable clinical translation including through our collaboration with the Moffitt Cancer Center, where we are evaluating AMP-boosting of CD19 CAR-T therapies to promote durable CAR-T responses to tumors. With many patients failing to enter remission with CAR-T therapy alone or relapsing due to poor CAR-T persistence, this could be the boost that immunotherapy needs."

Data Presentation Details:

Title: Lymph Node Targeted Boosting with Cognate Amphiphile-Peptide Vaccines Enhances TCR-T Cell Therapy to Eradicate Solid Tumors

Abstract Number: 157

AMP boosting significantly enhanced TCR-T cell anti-tumor response and led to durable cures of solid tumors in an established, syngeneic tumor model.
AMP boosting delivers cognate peptides and adjuvant to lymph nodes, which induces dendritic cell (DC) activation and provides in vivo activation of tumor-specific TCR-T cells to amplify anti-tumor potency of adoptively transferred cells.
AMP-peptide pulsed autologous human DCs enhanced the function of clinically relevant human KRAS-specific TCR-T cells in vitro.
These studies provide direct rationale and evidence for the combination of AMP boosting with TCR-T cell therapies to augment clinical responses.
Title: Amphiphile-Peptide Boosting with FMC63-binding Surrogate Peptide Mimotopes Induces Activation and Potent Effector Function in CAR-T Cells Targeting CD19

Abstract Number: 552

The AMP platform can potentially be utilized as a mechanism to expand and functionally enhance CAR-T cells in vivo targeting blood and solid tumors.
AMP-peptides (AMPlifiers) effectively accumulate in lymph nodes and decorate lymph node resident antigen-presenting cells (APCs) as well as boost CAR-T activation and expansion in vivo.
Phage display screening enables AMPlifier discovery and validation for CAR scFv domains such as FMC63, the CD19 specific domain used in marketed CD19 CAR-T products.
In vitro, CD19 AMPlifiers induce phenotypic activation, cytotoxic and effector function in cognate CD19 CAR-T cells with 28z or BBz signaling domains.
About the Amphiphile Platform

Our proprietary Amphiphile, or AMP, platform delivers investigational immunotherapeutics directly to the "brain center" of the immune system – the lymph nodes. We believe this site-specific delivery of disease-specific antigens, adjuvants, and other immunomodulators may efficiently educate, activate, and amplify critical immune cells, potentially resulting in induction and persistence of potent adaptive immunity required to treat many diseases. In preclinical models, we have observed lymph-node specific engagement driving therapeutic immune responses of increased magnitude, function, and durability. We believe our AMP lymph node targeted approach will produce superior clinical benefits compared to immunotherapies that do not engage the lymph nodes.

Our AMP platform, originally developed at the Massachusetts Institute of Technology, or MIT, has broad potential across cancers, infectious diseases and other disease indications to advance a number of development initiatives through internal activities, in-licensing arrangements or development collaborations and partnerships.

The Amphiphile platform is thought to deliver immunotherapeutics directly to the lymph nodes by latching on to the protein albumin, found in the bloodstream, as it travels to lymphatic tissue. In preclinical models, we have observed lymph-node specific engagement driving therapeutic immune responses of increased magnitude, function, and durability.

On November 12, 2021 Elevation Oncology, Inc. (Nasdaq: ELEV), a clinical stage biopharmaceutical company focused on the development of precision medicines for patients with genomically defined cancers, reported financial results for the quarter ended September 30, 2021 (Press release, Elevation Oncology, NOV 12, 2021, View Source;utm_medium=rss&utm_campaign=elevation-oncology-reports-third-quarter-2021-financial-results [SID1234595390]).

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"The third quarter was marked by continued progress on our mission to bring purpose-built medicines to patients with genomically defined cancers," said Shawn M. Leland, PharmD, RPh, Founder and Chief Executive Officer of Elevation Oncology. "The CRESTONE Study is now open and enrolling patients in the US, Canada, and Australia. Our collaboration with Caris Life Sciences is revealing a series of potential programs targeting genomic fusions. Finally, I am also pleased to welcome Valerie Malyvanh Jansen, MD, PhD, as our first Chief Medical Officer."

"We are encouraged by the durable clinical benefit seen with seribantumab in the case study of a patient with metastatic pancreatic cancer harboring an NRG1 fusion that was presented at the Australasian Gastro-Intestinal Cancer Trials Group conference," said Dr. Jansen. "Separately, we expect to complete enrollment of the first 20 patients in Cohort 1 of CRESTONE in mid-2022. We also anticipate presenting initial clinical data at a major medical meeting in mid-2022, which will include results from approximately 10 patients from Cohort 1 with meaningful follow-up who have been treated with seribantumab at 3 grams weekly."

Recent Business Highlights

Seribantumab

Case study of a patient with pancreatic cancer treated with seribantumab under a compassionate use program highlighted a confirmed partial response and durable clinical benefit, representing the first clinical data presented on the use of seribantumab in a patient with a tumor harboring an NRG1 fusion. Treatment with seribantumab was included as part of a case series presentation at the Australasian Gastro-Intestinal Trials Group (AGITG) 2021 Annual Scientific Meeting in October. A patient with treatment-refractory metastatic pancreatic cancer who had their tumor genomically profiled through the Cancer Molecular Screening and Therapeutics (MoST) program, was found to harbor an NRG1 fusion, and subsequently received treatment with seribantumab through a compassionate use program provided by Elevation Oncology. As of the data cut-off for the presentation, treatment with seribantumab resulted in durable clinical benefit for over 9 months, an approximately 90% reduction in the cancer biomarker CA19-9, and an ongoing 3 month confirmed partial response per RECIST criteria with a maximum tumor reduction of over 50%.
Launched additional global clinical trial sites in CRESTONE. The Company recently launched new clinical trial sites in Canada and Australia. CRESTONE is now open and enrolling patients at approximately 30 clinical trial sites across three countries. Through the "just-in-time" clinical site model in partnership with Caris Life Sciences, Tempus, and US Oncology, there are over 400 available sites that can be activated within the CRESTONE study.
Corporate

Strengthened corporate leadership. During the third quarter, the company announced Valerie Malyvanh Jansen, MD, PhD, as the company’s first Chief Medical Officer. Dr. Jansen was promoted from her prior role as Vice President, Clinical Development.
Upcoming Milestones

Complete enrollment of the first 20 patients in Cohort 1 of the CRESTONE study in mid-2022
Present initial clinical data from approximately 10 patients from Cohort 1 of the CRESTONE study treated with seribantumab at 3 grams weekly at a major medical meeting in mid-2022
Third Quarter 2021 Financial Results

As of September 30, 2021, the Company had cash and cash equivalents totaling $155.2 million, which is expected to fund current operations into the second quarter of 2023.

Research and development expenses for the third quarter 2021 were $9.3 million, compared to $2.6 million for the third quarter 2020. The increase in R&D expense was primarily related to an increase in manufacturing and clinical trial expenses associated with the CRESTONE study.

General and administrative expenses for the third quarter 2021 were $3.0 million, compared to $0.5 million for the third quarter 2020. The increase in G&A expense was primarily related to personnel costs, professional services and consulting, and other administrative costs.

Net loss for the third quarter 2021 was $12.3 million, compared to $3.0 million for the third quarter 2020.

About Seribantumab and NRG1 Gene Fusions

Seribantumab is a fully human IgG2 monoclonal antibody that binds to human epidermal growth factor receptor 3 (HER3). HER3 is traditionally activated through binding of its primary ligand, neuregulin-1 (NRG1). The NRG1 gene fusion is a rare genomic alteration that combines NRG1 with another partner protein to create chimeric NRG1 "fusion proteins". The NRG1 fusion protein is often also able to activate the HER3 pathway, leading to unregulated cell growth and proliferation. Importantly, NRG1 gene fusions are predominantly mutually exclusive with other known genomic driver mutations and are considered a unique oncogenic driver event associated with tumor cell survival.

NRG1 fusions have been identified in a variety of solid tumors, including lung, pancreatic, gallbladder, breast, ovarian, colorectal, neuroendocrine, cholangiocarcinomas, and sarcomas. In preclinical experiments, seribantumab prevented the activation of HER3 signaling in cells that harbor an NRG1 gene fusion and destabilized the entire ERBB family signaling pathway including the activation of HER2, EGFR, and HER4. In addition to extensive nonclinical characterization and testing, seribantumab has been administered to over 800 patients across twelve Phase 1 and 2 studies, both as a monotherapy and in combination with various anti-cancer therapies. Seribantumab is currently being evaluated in the Phase 2 CRESTONE study for patients with solid tumors of any origin that have an NRG1 fusion.

About the CRESTONE Study

Clinical Study of Response to Seribantumab in Tumors with Neuregulin-1 (NRG1) Fusions. CRESTONE is a Phase 2 tumor-agnostic "basket trial" of seribantumab in patients with solid tumors that harbor an NRG1 fusion and have progressed after at least one prior line of standard therapy. The primary objective of the study is to describe the anti-tumor activity and safety of seribantumab as a monotherapy specifically in patients whose solid tumor is uniquely driven by an NRG1 gene fusion. CRESTONE offers a clinical trial opportunity for patients with advanced solid tumors who have not responded or are no longer responding to treatment. Patients are encouraged to talk to their doctor about genomic testing of their tumor. CRESTONE is open and enrolling today in the United States, Australia, and Canada. For more information visit www.NRG1fusion.com.

On November 12, 2021 Cyteir Therapeutics, Inc. ("Cyteir") (Nasdaq: CYT), a company focused on the discovery and development of next-generation synthetically lethal therapies for cancer, reported financial results for the third quarter ended September 30, 2021 and provided an update on recent business highlights (Press release, Cyteir Therapeutics, NOV 12, 2021, View Source [SID1234595389]).

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"We continue to make significant progress in advancing the Phase 1/2 study of our lead program, CYT-0851, as we reached an important milestone with the identification of the Phase 2 dose," said Markus Renschler, MD, President and Chief Executive Officer of Cyteir. "The Cyteir team is excited to continue with the next steps of CYT-0851 clinical development as we advance the drug into the Phase 2 expansion cohorts as a monotherapy and as we initiate Phase 1 combination therapy with standard chemotherapy, with the ultimate goal of bringing the drug to patients in need."

Third Quarter and Recent Developments Business Review and Operational Updates

CYT-0851

Cyteir completed the dose-escalation portion of its Phase 1/2 study of CYT-0851 up to the maximum feasible daily dose of 1200 mg and declared the maximum tolerated dose of 600mg per day. Dose limiting toxicities of fatigue, vomiting, dehydration, dry skin, stomatitis, myalgia, and acidosis were observed at daily doses of 600mg and above. All were grade 3 events and reversible with dose interruption.

With the dose escalation portion of the study complete, the Phase 2 dose has been identified as 400 mg per day. We continue to enroll patients at the 400mg per day dose and below, to obtain additional safety, pharmacokinetic, and biomarker data. Simultaneously, we are initiating Phase 2 expansion study into disease-specific cohorts and expect to begin enrolling patients in the first quarter of 2022. We are also initiating a Phase 1 combination study of CYT-0851 with three standard-of-care regimens: rituximab plus bendamustine, gemcitabine and capecitabine, in both hematologic malignancies and solid tumors.

Pipeline

Investigational New Drug (IND)-enabling studies with CYT-1853 are ongoing and the Company expects to submit an IND application for CYT-1853 in 2022. Cyteir is also advancing preclinical studies on additional targets to nominate the next target from the Company’s DNA damage response platform.

Third Quarter Financial Results

Cash and cash equivalents: Cash and cash equivalents for the quarter ended September 30, 2021, were $199.8 million. The cash and cash equivalents total for the third quarter includes the $14.5 million in net proceeds raised from the partial exercise of the option to purchase additional shares of common stock by the underwriters of our IPO.

Research and development (R&D) expenses: R&D expenses were $8.2 million for the third quarter of 2021 versus $4.2 million for the same period in 2020. The year-over-year increase in R&D spending in the comparative periods was due primarily to increased R&D and clinical activity and increased headcount.

General and administrative (G&A) expenses: G&A expenses were $3.5 million for the third quarter of 2021 compared to $0.8 million for the same period in 2020. The year-over-year increase in G&A expenses in the comparative periods was primarily due to increased headcount, as well as increased professional fees and other administrative expenses associated with company growth and operating as a public company.

Net loss: Net loss was $11.7 million, or $0.33 per share in the third quarter of 2021 compared to $5.0 million, or $3.44 per share in the third quarter of 2020.

On November 12, 2021 Checkmate Pharmaceuticals, Inc. (Nasdaq: CMPI) ("Checkmate"), a clinical stage biopharmaceutical company focused on developing its proprietary technology to harness the power of the immune system to combat cancer, reported third quarter 2021 financial results and provided a business update (Press release, Checkmate Pharmaceuticals, NOV 12, 2021, View Source [SID1234595388]).

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"We are excited about the future of vidutolimod as a potential novel treatment for multiple tumor types, including melanoma and head and neck cancer. We continue to advance our clinical trials towards potential data readouts in 2022," said Alan Fuhrman, interim President and Chief Executive Officer of Checkmate.

Recent Business Updates

During The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting, Dr. John Kirkwood from the University of Pittsburgh Medical Center presented a poster on the final clinical data from the Phase 1b study of vidutolimod in combination with pembrolizumab or as a monotherapy in patients with anti-PD-1 refractory melanoma.
Vidutolimod in combination with pembrolizumab led to an ORR of 23.5% by RECIST v1.1, a complete response rate of 7.1%, and a median duration of response of 25.2 months.
Vidutolimod monotherapy resulted in a 20.0% ORR by RECIST v1.1 and a median duration of response of 5.6 months.
The most frequent treatment-related adverse events were consistent with flu-like symptoms and injection site reactions and were most commonly Grade 1 or 2.
We appointed Alan Fuhrman, an experienced biotech executive and Checkmate board member, as interim President and CEO.
Ongoing patient recruitment activities and enrollment across our clinical trials evaluating vidutolimod, including:
A Phase 2 trial of vidutolimod in combination with nivolumab in anti-PD-1 refractory advanced melanoma, supported by a clinical collaboration with Bristol Myers Squibb.
A randomized Phase 2/3 trial of vidutolimod in combination with nivolumab vs. nivolumab monotherapy in first-line metastatic or unresectable melanoma, also supported by the clinical collaboration with Bristol Myers Squibb.
A Phase 2 trial of vidutolimod in combination with pembrolizumab in recurrent or metastatic squamous cell head and neck cancer.
Start-up activities underway for the planned expansion of the development program for vidutolimod in combination with cemiplimab in cutaneous squamous cell carcinoma and Merkel cell carcinoma, supported by a clinical collaboration with Regeneron.
Third Quarter 2021 Financial Results

Research and development expenses (R&D): R&D expenses for the three months ending September 30, 2021, were $11.4 million, compared to $6.7 million for the same period in the prior year. This increase reflects higher third-party CRO and manufacturing costs directly related to the vidutolimod clinical trials, in addition to higher personnel and operating expense for the planning and execution of the clinical trials.
General and administration expenses (G&A): G&A expenses for the three months ending September 30, 2021, were $3.6 million, compared to $3.2 million for the same period in the prior year. This increase was primarily attributable to increases in personnel and operating expense incurred in connection with Checkmate operating as a publicly traded company.
Cash, cash equivalents and investments: Cash, cash equivalents and available-for-sale investments were $80.8 million as of September 30, 2021.

On November 12, 2021 Cellectis S.A. (NASDAQ: CLLS – EURONEXT GROWTH: ALCLS) (the "Company"), a clinical-stage gene-editing company employing its core technology to develop products based on gene-editing with a portfolio of allogeneic chimeric antigen receptor (CAR-)T cells in the field of immuno-oncology and gene-edited hematopoietic stem cells in other indications, reported the first preclinical data on UCARTMESO, its allogeneic CAR-T cell product candidate targeting mesothelin, being developed for patients with mesothelin-expressing solid tumors (Press release, Cellectis, NOV 12, 2021, View Source [SID1234595387]).

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The data were presented today in a poster session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting titled "Mesothelin (MSLN) targeting allogeneic CAR-T cells engineered to overcome tumor immunosuppressive microenvironment". Poster # 143.

The poster presentation highlighted the following preclinical data:

Mesothelin is an interesting target for CAR-T cell therapy for solid tumors because it is highly and consistently expressed in mesothelioma and pancreatic cancers. It is also over-expressed in subsets of other solid tumors (ovarian cancer, non-small cell lung cancer, gastric cancer, triple-negative breast cancer) while modestly expressed in healthy cells, indicating that targeting mesothelin may result in a safe and effective therapy.
UCARTMESO product candidate is composed of allogeneic non-alloreactive T cells edited with TALEN-encoding mRNAs to disrupt TRAC, CD52 and TGFBR2 genes, and transduced ex vivo with a recombinant lentiviral vector (rLV) to express a second-generation CAR targeting MSLN. It is the first TALEN-induced triple knock out (KO) product candidate in the allogeneic CAR-T space.
The preclinical data demonstrated potent activity of UCARTMESO in vitro and in vivo against MSLN expressing cell lines, and in vivo activity in pancreatic and pleural mesothelioma mouse models.
Due to TGFBR2 KO, UCARTMESO was shown to restore IL2RA upregulation upon in vitro activation, even in media rich in TGFB1, which contributes to the immune suppressive microenvironment in tumors.
Laurent Poirot, PhD, Senior Vice President Immunology, noted: "Overall, the data demonstrated that the TGFBR2 gene knock out provides valuable additional properties to UCARTMESO, which may result in a very effective therapy despite an immune suppressive tumor microenvironment, and supports its clinical development for the treatment of solid tumors."

A copy of the presentation will be available on Cellectis’ website here, shortly after the event.