On November 10, 2022 Catamaran Bio, Inc., a biotechnology company developing off-the-shelf NK cell therapies to treat cancer, reported new data demonstrating preclinical efficacy of two CAR-NK cell therapies in solid and hematological cancers (Press release, Catamaran Bio, NOV 10, 2022, View Source [SID1234623770]). The data are being presented in two posters at the Society for Immunotherapy in Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting, being held in Boston, Massachusetts, November 8-12, 2022.

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"Collectively, these preclinical data sets demonstrate the power of Catamaran’s fully-integrated TAILWIND platform to deliver allogeneic NK cell therapies for solid tumors," said Vipin Suri, PhD, MBA, Chief Scientific Officer of Catamaran Bio. "We have now shown preclinical efficacy in multiple xenograft models with two differentiated CAR-NK cell therapies engineered with the functional attributes necessary for durable efficacy in solid tumors and manufactured using an efficient non-viral cell engineering system."

Data supporting Catamaran’s lead program, CAT-248, will be presented in a poster titled "Engineering CD70-directed CAR-NK cells for the Treatment of Hematological and Solid Malignancies." Highlights include:

The non-viral TcBuster Transposon System was used to deliver transposons containing a CD70 CAR or CD70 CAR/IL15 expression cassette in primary human peripheral blood NK (PBNK) cells.
Knockout of CD70 via CRISPR/Cas9 in CD70 CAR-expressing NK cells mitigated fratricide and increased cell yield.
Engineered cells were highly cytotoxic against multiple CD70-positive tumor cells lines derived from renal cell carcinoma (RCC) and acute myeloid leukemia (AML).
A single dose of engineered NK cells expressing CD70 CAR and secreted IL15 reduced tumor burden and increased survival in an RCC xenograft model, without the need for exogenous IL15.
These results demonstrate the potential for targeting CD70 with CAR-NK cell therapy for the treatment of AML, RCC, and other CD70-positive malignancies while overcoming fratricide issues by engineering with a non-viral transposon delivery system in combination with CRISPR/Cas9 editing.

Data from a second CAR-NK cell therapy construct engineered using the TAILWIND platform are presented in a poster titled "Allogeneic Natural Killer Cells Engineered to Express HER2-directed CAR, Interleukin-15 and TGFβ Dominant Negative Receptor Effectively Control HER2+ Tumors." Highlights include:

The non-viral TcBuster Transposon System enabled high efficiency engineering of a large multi-cistronic cargo containing HER2-CAR, IL15, and TGFβ-DNR. Transposon engineering of CAT-179 resulted in stable expression of the CAR without the need for post-engineering selection.
CAT-179 demonstrated HER2-CAR-driven interferon gamma (IFNγ) production and tumor cell killing in vitro when co-cultured with HER2+ tumor cells.
CAT-179 was resistant to TGFβ-mediated immunosuppression in vitro, indicating that the cells will be protected from TGFβ-mediated immune suppression in the tumor microenvironment.
Engineering of IL15 in CAT-179 significantly enhanced NK cell persistence and in vitro and in vivo and eliminated the need for exogenous cytokine support.
CAT-179 showed potent anti-tumor activity in vivo against a xenografted HER2+ N87 gastric cancer cell line and led to a significant survival benefit in tumor-bearing mice.
These results demonstrate that NK cells engineered via the TAILWIND platform have a favorable pharmacologic profile and the potential for treatment of solid tumors.

On November 10, 2022 Parthenon Therapeutics, a precision oncology company inventing a novel class of anti-cancer therapies that reprogram the tumor microenvironment (TME), and ImaginAb Inc., a global biotechnology company developing 89Zr crefmirlimab berdoxam (CD8 ImmunoPET) imaging agent and next generation radiopharmaceutical therapies (RPT) products, reported that the companies have entered into a multi-year, non-exclusive license and supply agreement (Press release, Parthenon Therapeutics, NOV 10, 2022, View Source [SID1234623769]). Under the agreement terms, Parthenon will use ImaginAb’s CD8 ImmunoPET imaging technology in its Phase 1 trial evaluating its lead compound, PRTH-101, which is expected to begin in 2023.

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"Parthenon is developing an entirely new class of anti-cancer therapies that can modulate the TME in immune-excluded tumors through our proprietary approach that utilizes biomarkers to match our therapeutic approaches to individual patients based on the specific characteristics of their cancer," said Laurent Audoly, Ph.D., Chief Executive Officer and Co-Founder of Parthenon Therapeutics. "ImaginAb’s CD8 ImmunoPET technology will provide us with critical insight into the infiltration of CD8 T cells in the TME, not only for a small part of a single lesion but also for an entire tumor as well as all tumors throughout a patient’s body. This approach is less invasive compared to the current biopsy-based standard of care and is consistent with the objective of generating a rich dataset of biomarker endpoints leveraging orthogonal approaches in the earliest phases of our clinical trial. PRTH-101 targets discoidin domain receptor 1 (DDR1) to punch holes in the mechanical barrier that characterizes immune-excluded tumors, thereby making them vulnerable to attack by the immune system. The CD8 ImmunoPET data will be used in our Phase 1 trial to quantify the degree of immune infiltration into tumors before and after dosing and be used to identify tumors that are ‘hot’, ‘cold’ or ‘immune excluded’. This knowledge will help us design a clinical strategy to focus on those patients who will benefit the most from treatment with PRTH-101."

Hot tumors are characterized by the presence of CD8+ T cells that are able to infiltrate the tumor parenchyma. These tumors often respond to immune checkpoint inhibitors, unlike cold tumors which have few to no CD8+ T cells. In contrast to both hot and cold tumors, immune excluded tumors have CD8+ T cells in the tumor bed, but these cells are relegated to the tumor stroma by collagen and/or other barriers, thereby preventing them from interacting with tumor cells to perpetuate an anti-tumor response. PRTH-101 targets the collagen barrier of immune excluded tumors, thereby enabling CD8+ T cells to interact with and kill tumor cells. Immune-excluded tumors can represent up to 75 percent of a TME phenotype across different tumor types highlighting the potential for identifying therapeutics that can help many patients.

"We are excited to provide our cutting edge CD8 imaging technology to Parthenon which allows changes in CD8+ T-cell distribution to be visualised before and after therapy," said Ian Wilson, Chief Executive Officer of ImaginAb. "Parthenon joins an increasing number of pharma and biotech companies incorporating our CD8 ImmunoPET agent into their clinical trials to precisely understand the therapeutic activity and treatment outcomes of investigational novel oncology assets in cancer patients at a very early stage. CD8+ T-cells play a pivotal role in immunotherapy and CD8 ImmunoPET has demonstrated the potential to track CD8+ T-cells using whole body PET scans in clinical trial subjects."

Under the terms of the agreement, ImaginAb will supply clinical doses of its investigational CD8 ImmunoPET technology to Parthenon Therapeutics for use in the clinical development of PRTH-101 at clinical trial sites across the United States. Initially, Parthenon Therapeutics will investigate CD8 status in a Phase I dose escalation clinical trial of PRTH-101, both in monotherapy and in combination with anti-PD(L)1 therapy. The trial is expected to initiate in 2023, with the ability to add dose expansion cohorts at a later date to explore additional rational combination opportunities and tumor types.

ImaginAb will receive payments for providing dose manufacturing and ongoing technical, clinical and regulatory support to enable the successful implementation of its CD8 ImmunoPET technology into Parthenon Therapeutics’ clinical trials.

ImaginAb is actively investing in the clinical and global supply chain development of CD8 ImmunoPET agent to provide simple turnkey access to its novel technology for use in clinical research and development. By collaborating with leading biotech companies, ImaginAb is making progress towards the company’s goal of being a key partner in the development of new immunotherapies across multiple cancer types and geographies.

On November 10, 2022 RootPath, a synthetic biology company that elevates the throughput of gene function interrogation by orders of magnitude, reported the presentation of data on tumor reactivity in various applications via its PathFinder DNA AssemblyTM technology in three posters at the 37th Annual Meeting of the Society for Immunology of Cancer (SITC) (Free SITC Whitepaper) in Boston, Massachusetts (Press release, RootPath, NOV 10, 2022, View Source [SID1234623767]).

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"The posters that we are presenting at SITC (Free SITC Whitepaper) continue to demonstrate the power of RootPath’s platform and approach to transformative cell therapies," said Xi Chen, Co-founder and CEO of RootPath. "This showcases the efficiency and unmet need for our PathFinder DNA AssemblyTM technology along with its potential to target various tumor types through multiple applications. We are pleased that data continue to validate our platform, which can identify tumor reactive TCRs at unprecedented scale."

The first presentation provides an overview of an unbiased survey of tumor reactivity and the transcriptional landscape of 1,000 clones of PD-1hi T-cells from peripheral blood during ICB treatment and reveals the breadth and dynamics of anti-tumor immunity. Previous studies have demonstrated that PD-1 may be a biomarker for tumor reactive T-cells in peripheral blood. Using its novel PathFinder DNA AssemblyTM technology, RootPath surveyed 1,000 TCRs from peripheral bulk and PD-1hi T-cells from a melanoma patient before and after ICB treatment. Data show that validated tumor-reactive TCRs do not reside in a single scRNA-Seq cluster and are present before and after ICB therapy. These experiments, enabled by RootPath’s technology, enable the high-throughput discovery of tumor reactive TCRs from the blood and build the foundation for a personalized cell therapy that does not rely on access to the tumor.

The second presentation covers rapid discovery of personalized TCRs through a single-cell transcriptomic signature predicting tumor reactivity. The ideal cell therapy is potent, polyclonal, and proliferative while still being efficient to manufacture. To enable this, RootPath uses its TCR synthesis, screening technology, and reactivity database to develop a gene signature, Interpreter, that predicts tumor reactivity from single cell sequencing data. The company demonstrates the ability of Interpreter to accurately call tumor reactive T cells in a liver cancer patient and validate the TCR reactivity by ELISpot assays, and also shows the utility of Interpreter to quickly identify tumor-reactive TCRs without experimentation for a synthetic TIL product that is highly enriched for reactivity and in an improved cell phenotype.

The third presentation showcases antigen-agnostic discovery of tumor-reactive TCRs powered by repertoire-scale TCR gene synthesis and the use of banked allogeneic cancer cell lines revealing anti-tumor responses. The rare tumor-reactive T cells within the tumor-infiltrating lymphocyte (TIL) population are mediators of natural and therapy-induced anti-tumor responses. The enhancement and expansion of these elusive cells became a focus of recent innovations in immuno-therapy. However, most approaches focus on neoantigen-reactive T cells and overlook the equally important T cells that recognize wildtype tumor-associated antigens (TAAs) partly because most TAAs are yet to be discovered. RootPath established a method to screen thousands of TIL-derived TCRs against banked allogeneic tumor cell lines, which likely express many known and unknown TAAs that are expressed by the patient’s autologous tumor. A key to this method is to "HLA-personalize" the allogeneic tumor cell lines. RootPath has successfully identified multiple TCRs that are reactive to both autologous tumor and multiple cell lines.

On November 10, 2022 Delphinus Medical Technologies reported the installation of its SoftVue 3D Whole Breast Ultrasound Tomography System (SoftVue) at East Alabama Medical Center, making the site the second in the world to purchase and offer patients the FDA-approved technology for screening women with dense breast tissue (Press release, Delphinus Medical Technologies, NOV 10, 2022, View Source [SID1234623766]).

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Dense breast tissue is common, affecting 40 percent of women and making them four times more likely to develop breast cancer. Compounding the increased risk, dense breast tissue typically appears white on a mammogram, as does cancer, making clinicians miss roughly half of new cancer cases.

When paired with a screening mammogram, SoftVue has been shown to identify up to 20 percent more cancers while also reducing false positives and decreasing unnecessary call-backs and biopsies.

"We developed SoftVue to fit a very real unmet need for patients with dense breasts who need better screening modalities that can find more cancers," Mark J. Forchette, president and CEO, Delphinus Medical Technologies, Inc. "As an Auburn University graduate, I am excited that the East Alabama community is at the forefront of dense breast screening innovation and has an opportunity to lead a global transformation in imaging that will save hundreds of thousands of lives."

The FDA approval of SoftVue, used as an adjunct to mammography, allows women with dense breast tissue to have both cancer screening tests during a single appointment. Taking approximately eight to 10 minutes, a SoftVue exam uses warm water and ultrasound technology to create a 3D image of the whole breast to detect the presence of cancer in its earliest stages — including masses in dense breast tissue often missed by mammography alone — while avoiding radiation exposure and compression, allowing the radiologist to make a more accurate diagnosis.

"We are committed to providing our patients with superior screening technology. SoftVue will further strengthen our fight against breast cancer, which accounts for one in three new cancer diagnoses in women each year," said Laura Grill, East Alabama Health president and CEO. "The key to breast cancer survival is early detection, and this new screening device will be lifesaving for so many women in our community."

On November 10, 2022 Aura Biosciences Inc. (NASDAQ: AURA), a clinical-stage biotechnology company developing a novel class of virus-like drug conjugate (VDC) therapies for multiple oncology indications, reported that it has initiated startup activities for the global Phase 3 trial. After presenting positive interim data at the American Academy of Ophthalmology from its ongoing Phase 2 trial, Aura has aligned with regulatory agencies and finalized the design of the global Phase 3 trial (Press release, Aura Biosciences, NOV 10, 2022, View Source [SID1234623765]). The trial will evaluate the efficacy and safety of belzupacap sarotalocan (bel-sar) with suprachoroidal administration, for the first-line treatment of early-stage choroidal melanoma (CM).

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"Finalizing the study design and selecting the optimal route of administration for the Phase 3 trial are key milestones in progressing towards a potential approval for bel-sar as a first-line vision preserving therapy in patients with early-stage choroidal melanoma," said Dr. Cadmus Rich, Chief Medical Officer of Aura Biosciences. "We are pleased to have aligned with regulatory agencies on the overall Phase 3 trial design, including the primary and key secondary endpoints. We remain focused on improving the standard of care for patients with early-stage choroidal melanoma, a life-threatening disease that has no approved therapies."

The Phase 3 trial has a three arm randomized and masked design, where the primary analysis will compare bel-sar to sham. Aura is planning to enroll approximately 75 adult patients with eary-stage CM, including patients with indeterminte lesions and small choroidal melanoma. Patients will be enrolled with documented growth as an enrichment strategy intended to increase the efficiency of the trial which will include an adaptive design to further increase the probability of success.