On November 15, 2022 ElevateBio, LLC (ElevateBio), a technology-driven company focused on powering transformative cell and gene therapies, and Affini-T Therapeutics, a biotechnology company unlocking the power of T cells against oncogenic driver mutations, reported a partnership to advance Affini-T’s engineered TCR-T therapies focused on KRAS (Kirsten rat sarcoma viral oncogene homolog), one of the most prevalent oncogenic driver mutations in solid tumor cancers (Press release, ElevateBio, NOV 15, 2022, View Source [SID1234624111]). Affini-T will leverage ElevateBio BaseCamp’s LentiPeakTM lentiviral vector technology platform and cell therapy production capabilities to advance its investigational oncogenic driver programs into clinical development. ElevateBio BaseCamp is a purpose-built viral vector and cell therapy center of excellence with end-to-end process development and current Good Manufacturing Practice (cGMP) manufacturing capabilities for research, clinical and commercial cell and gene therapies, and regenerative medicines.

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"Affini-T is pioneering novel T cell therapy approaches to treat solid tumor cancers by striking at the core of tumor biology, which entails leveraging the most advanced tools and techniques in cell engineering," said Kim Nguyen, Ph.D., Chief Technical Officer, Affini-T Therapeutics. "Deep expertise in autologous cellular therapies manufacturing and analytics combined with its scalable platform for suspension-based lentiviral production, make ElevateBio an ideal partner as we progress our oncogenic driver programs into the clinic and work to deliver transformative therapies to patients and their families."

"We are pleased that our LentiPeak platform and cell therapy expertise can enable innovative developers like Affini-T to further accelerate their pipeline and look forward to working together so that we can bring forth these important therapies for difficult to treat solid tumors," said David Hallal, Chairman and Chief Executive Officer of ElevateBio. "At ElevateBio, we’ve combined multiple next-generation technology platforms with industry-leading expertise to transform the current cell and gene therapy development paradigm and provide our partners with a strategic advantage in the development of their therapies, and ultimately improve the speed of novel therapies to patients."

Affini-T’s proprietary platform is designed to select and engineer the right immune cells to orchestrate a durable and coordinated immune response within the immunosuppressive tumor microenvironment. The company is pioneering engineered T cell therapies with cutting-edge synthetic biology and gene editing enhancements to target oncogenic driver mutations at the core of tumor biology. Its engineered cell therapies are designed to overcome the immunosuppressive tumor microenvironment, enhancing T cell function to increase durability, build persistent responses, and augment tumor infiltration. Affini-T’s investigational cell therapies have the potential to offer new treatment options for patients affected by cancer with mutant variants of KRAS, which account for up to 30% of all cancers and are particularly frequent in cancers with high mortality rates, including lung cancer, colorectal cancer, and pancreatic cancer.

On November 15, 2022 Casma Therapeutics, Inc., a biotechnology company engaging the autophagy system to provide innovative new medicines, reported the closing of a Series C financing round of $46.0 million (Press release, Casma Therapeutics, NOV 15, 2022, View Source [SID1234624110]). New investors participating in the round include Amgen Ventures, LLC, Astellas Venture Management, Eisai Co., Ltd., Euclidean Capital, Mirae Asset, and Ono Venture Investment. Current investors Eventide Asset Management, LLC, Schroders Capital, The Column Group, Third Rock Ventures, and other funds also participated in the financing. Dr. Hiromichi Kimura, Investment Director of Astellas Ventures, has joined the board of directors. Dr. Tomotaka Okino of Ono Venture Investment and Amgen Ventures have joined as board observers.

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Casma will use proceeds to advance its lead program for MYD88 mutant lymphoma through preclinical and into IND enabling studies.

"The closing of this financing has strengthened our resources to continue advancing our drug pipeline focused on autophagy-based degradation," said Keith Dionne, Ph.D., Chief Executive Officer of Casma Therapeutics, Inc. "We are thrilled to welcome several top-tier investors who recognize the potential of our biological platforms and therapeutic assets targeting well-known high-value and traditionally undruggable targets."

"Casma’s autophagy-based degradation platform, PHLYT, is unique and impressive," commented Dr. Kimura. "Along with a rich pipeline of autophagy degraders, the company has also established a highly qualified team with extensive scientific experience in drug development. We expect that this round of funding will accelerate development of Casma’s pipeline assets, especially its degrader for MYD88 mutant tumors."

On November 15, 2022 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported new data showing how the Company’s DecisionDx-SCC test can provide objective, independent and significant risk-stratification for cutaneous squamous cell carcinoma (cSCC) tumors with uncertainty in differentiation status (Press release, Castle Biosciences, NOV 15, 2022, View Source [SID1234624109]). The data were shared in an oral presentation given at the American Society of Dermatopathology (ASDP) 59th Annual Meeting by Sarah Estrada, M.D., dermatopathologist with Affiliated Dermatology in Scottsdale, Arizona.

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Overall, these data demonstrate how DecisionDx-SCC can significantly stratify the risk of metastasis in high-risk cSCC patients with an ambiguous tumor differentiation status. Additionally, the study suggests that incorporating the test’s results into clinical cSCC risk assessments could improve risk-stratification and enhance current patient management decisions to improve patient outcomes.

Subjective pathology variability in the histologic grading of cSCC tumors is an important clinical issue, particularly when comparing moderately differentiated tumors. Poor differentiation has been shown to be an independent risk factor associated with poor patient outcomes.1–3 However, there is a lack of consistency in differentiation assessment4 which can adversely impact the value of differentiation as a prognostic factor. In fact, the two most widely used cSCC staging systems, American Joint Committee on Cancer Staging Manual Eighth Edition (AJCC8) and Brigham and Women’s Hospital (BWH), vary on their inclusion of poor differentiation as a risk factor for staging; BWH includes it, while AJCC8 does not.

"A single clinicopathologic risk factor, including a cSCC tumor’s differentiation status, can affect staging and thereby escalate or deescalate patient treatment plans," commented Estrada. "Objective risk-stratification that is independent of clinicopathologic factors and staging, as provided by DecisionDx-SCC test results, can identify high-risk cSCC lesions and provide clarity in challenging staging situations."

The presentation, titled "Incorporating the 40-GEP test for poorly differentiated cutaneous squamous cell carcinoma (cSCC) tumors mitigates risk assessment uncertainty from histologic grading," describes the results of a study involving a cohort of 420 high-risk cSCC patients divided into either moderately or poorly differentiated statuses, based on their pathology report and review by an independent dermatopathologist.

A sub-cohort of 171 tumors with differentiation uncertainty was then staged using BWH criteria. The differentiation status of the tumors in this "differentiation uncertainty cohort" was then manually changed so that poorly differentiated was changed to moderately differentiated and vice versa, and changes to BWH staging were analyzed.

The study data showed that:

For 40% of patients in the sub-cohort, the BWH stage changed based upon the alteration of differentiation status, which could impact treatment decisions.
DecisionDx-SCC independently and significantly stratified the sub-cohort according to metastatic risk; patients with a low-risk (Class 1) result had a statistically significant higher three-year metastasis free survival than both moderate-risk (Class 2A) and high-risk (Class 2B) patients (90.1% vs. 78.6% and 62.5%, respectively; p=0.02).
About DecisionDx-SCC

DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous squamous cell carcinoma metastasis for patients with one or more risk factors. The test result, in which patients are stratified into a Class 1 (low), 2A (moderate) or 2B (high) risk category, predicts individual metastatic risk to inform risk-appropriate management.

Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that integrating DecisionDx-SCC with current prognostic methods can add positive predictive value to clinician decisions regarding staging and management.

On November 15, 2022 Propanc Biopharma, Inc. (OTC Pink: PPCB) ("Propanc" or the "Company"), a biopharmaceutical company developing novel cancer treatments for patients suffering from recurring and metastatic cancer, reported that the Company’s lead product candidate, PRP, could enhance the effects of novel therapies like immune checkpoint inhibitors that can have a role in pancreatic cancer treatment (Press release, Propanc, NOV 15, 2022, View Source [SID1234624108]). Chief Scientific Officer and Co-Founder, Dr. Julian Kenyon MD, MB, ChB, predicts therapies can enhance the patient’s immune response to fight solid tumors by enabling detection of specific tumor cells within the body that were previously undetected. For example, once considered a "non-immunogenic" cancer, pancreatic ductal adenocarcinoma (PDA) has been identified with upregulated immune networks and immune checkpoint molecule expression in its tumor microenvironment and is now redefined as an immunogenic cancer, according to the World Journal of Gastroenterology, November 21, 2016.

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PDA is a highly aggressive malignancy, characterized by delayed diagnosis and treatment resistance. At the time of clinical detection, most PDA cancers are either advanced locally, or metastatic, i.e., ineligible for surgical resection and with a typical five-year survival in the single digits. One of the reasons for the poor effect of treatment is the ability of PDA to evade host immune surveillance. The tumor microenvironment of PDA is composed of a dense fibrotic stroma of extracellular (outside cell) matrix components and a variety of inflammatory cells. "This is where PRP comes in, and, as we understand, it can potentially expose the tumors and lower drug resistance, whereas before they were largely impenetrable," said Dr. Kenyon.

PRP was recently reported as having a significant impact on the tumor microenvironment by impact inhibiting, slowing, or reversing tumor development through acting as an anti-tumor agent, decreasing tumor cell proliferation, developing a non-malignant phenotype (observable characteristics) and promoting cell adhesion (sticking close to one another) and differentiation (cell specialization rather than stem cell-like). To accomplish this, PRP targets specific pathways like TGFβ, critical for tumor development and prevention of immunorecognition by the body’s own immune system. Furthermore, numerous pathways affected downstream are also impacted by altering the tumor surface, which is often resistant to immune regulators due to the impenetrability of the tumor walls.

"Immune checkpoint inhibitors have only recently been investigated for solid tumors like PDA and we are now only realizing the importance of the immune checkpoint inhibition in these cancers. PRP, which is a combination of two proenzymes, trypsinogen and chymotrysinogen, has been shown to impact the tumor microenvironment dramatically, which could have significant implications for other treatment modalities, such as chemotherapy, but also immune checkpoint inhibitors, which could result in improved effects," said Dr. Kenyon. "As we progress along the clinical development pathway, we will continue to explore combinatorial treatments that, if proven clinically beneficial, could have a marked impact on the response rates of approaches like immune checkpoint therapy and lead to improved benefits for sufferers."

PRP is a mixture of two proenzymes, trypsinogen and chymotrypsinogen from bovine pancreas, administered by intravenous injection. A synergistic ratio of 1:6 inhibits growth of most tumor cells. Examples include kidney, ovarian, breast, brain, prostate, colorectal, lung, liver, uterine and skin cancers.

On November 15, 2022 Medigene AG (Medigene, FSE: MDG1, Prime Standard), an immuno-oncology company focused on the development of differentiated, best-in-class T Cell Receptor engineered T cell (TCR-T) therapies, reported an updated corporate strategy to drive and expedite the development of novel therapies for the treatment of multiple solid tumor indications with high unmet need (Press release, MediGene, NOV 15, 2022, View Source [SID1234624107]).

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"We are excited to announce this strategy and corporate update for Medigene," said Dr. Selwyn Ho, MB BS, Chief Executive Officer at Medigene. "At the heart of our work is our extensive expertise on T cell immunology and many years of development of a proprietary, innovative "end-to-end" platform under the leadership of our Chief Scientific Officer, Prof. Dolores Schendel.

With the platform containing multiple combinable technologies that optimize the development of, as well as enhance the TCR-T products from both an activity and potential safety perspective, we believe that our emerging TCR-T therapies have the potential to address the significant challenges that solid tumors create for immunotherapies, and improve clinical outcomes. The robustness of our work has been well validated through multiple partnerships where potentially highly differentiated TCRs and novel individual technologies have been licensed from Medigene, as well as through the success of our MDG1011 phase 1 trial.

We are focused on delivering best-in-class TCR-T therapies to patients suffering from difficult to treat tumors and have accelerated and prioritized our research activities. Our lead program, MDG1015, is a 3rd generation TCR-T therapy that combines a novel TCR against NY-ESO-1, a well-characterized and validated cancer antigen expressed in multiple tumor types, with the PD1-41BB Switch Receptor that significantly improves the ability of our TCR-T cells to kill cancer cells. This program has the potential for a more targeted, safer, and potent immune response while overcoming highly immunosuppressive tumor microenvironment.

To support our efforts, we continue to strengthen our leadership team and have appointed Mr. James Cornicelli as Head of Corporate Development and Strategy. As a highly seasoned executive with over 20 years in senior business development and strategic advisory roles, Mr. Cornicelli brings multiple areas of expertise that will help guide our company on critical decisions about partnering and accelerate our growth strategy."

Strategic Actions Summary:

TCR-T Therapies Central to Medigene’s Approach
Medigene’s strategy will focus on developing best-in-class T Cell Receptor engineered T cell (TCR-T) therapies. TCR-T therapies are a novel class of cellular immunotherapy with the ability to engage both surface and intracellular antigens on target cells, unlike CAR-T cell-based therapies, allowing for solid tumor targeting in a highly specific manner. The first generation of TCR-T therapies have shown improvements in outcomes in solid tumor clinical trials; however, unmet needs remain for further improvements in efficacy, that are sustained and with a lower risk of adverse effects.

Pipeline Expansion and Acceleration of Discovery Programs MDG1015 and MDG10xx
MDG1015, the company’s lead program, consists of a novel TCR against NY-ESO-1 (New York esophageal squamous cell carcinoma 1), a well-characterized cancer testis antigen (CTA) expressed in multiple tumor types combined with our PD1-41BB Switch Receptor technology, which blocks the PD1/PD-L1 inhibitory axis between T cells and tumors and activates the 41BB co-stimulatory pathway in TCR-T cells. This co-stimulation and reduced inhibition, help mitigating the negative effects of the solid tumor microenvironment, leading to multiple improvements in the activity of MDG1015, including improved tumor cell killing, greater effector T cell function, and enhanced T cell proliferation. For MDG1015 we expect a CTA / IND filing in 2H 2024.

MDG10xx is our second newly announced TCR-T therapy program against several undisclosed targets, in combination with the PD1-41BB Switch Receptor technology. The selection of a lead candidate for MDG10xx is planned for the second half of 2023.

Advancing Broad, Proprietary "End-to-End" Platform
Medigene’s "end-to-end" platform provides multiple combinable, exclusive, and proprietary technologies to create potential best-in-class TCR-T therapies to address the unmet needs in the treatment of solid tumors. The platform includes technologies that both help optimize our development activities as well as to enhance our TCR-T therapy products, during the stages of target screening, TCR generation, TCR-Therapy optimization, manufacturing, and clinical development. These include:

EXPItope-M: Proprietary in silico tool to identify immunogenic epitopes as potential TCR target specificities.
Allo-HLA TCR priming technology: Generation of high-affinity natural TCRs, for improved sensitivity and safety, by bypassing the thymic selection
CrossTAg vector system: Technology loads antigen on both HLA Class I and Class II complexes in antigen-presenting cells (APCs), creating stronger and more sustained immune responses
JOVI-Tag: Tool allowing standardized enrichment and tracking of recombinant TCR (rTCR) -expressing T cells to enable selection of safer TCRs when using HTS
PD1-41BB Co-Stimulatory Switch Receptor: A novel, highly innovative receptor that enhances TCR-T cell functionality, enabling it to mitigate against immunosuppressive tumor microenvironment (TME) and improves efficacy and sustained immune responses
Precision Pairing: Enables the modification and tailoring of TCR constant regions to improve pre-clinical efficacy through the enhanced anti-tumor functional activity of TCR-T cells and potential for improved safety by reducing the potential for off-target effects
Inducible iM-TCR: Control mechanism to regulate TCR-T therapy efficacy & safety, to avoid T cell exhaustion, cell death, and a loss of efficacy as well as to prevent over-activation of TCR-T which can mediate inflammatory responses in off-target tissues
Medigene is also currently developing additional novel and complementary technologies to add to our platform that will further optimize the development of and continue to enhance our TCR-T therapies.

Strengthening & Expanding our Partnership Approach By Leveraging our Innovative Assets & Technologies
To date, multiple partnerships have been established that validate our "end-to-end" platform assets and technologies, including with BioNTech, 2SeventyBio, and Hongsheng Sciences. Medigene will continue to work closely with our existing partners and explore new partnership opportunities to maximize the value of our current and future assets and technologies and ultimately deliver novel and differentiated TCR-T therapies to patients.

Focus on Solid Tumors
As previously announced, we have successfully completed our phase 1 MDG1011 program in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). The MDG1011 trial provides clear clinical validation of our ability to generate and manufacture TCR-T therapies and details of our manufacturing process have been shared at the Cell UK meeting in London, in November 2022 with the presentation available on Medigene’s website. The expanded clinical dataset from the trial will be available in due course.

Despite this positive trial for MDG1011, as previously disclosed, we have focused any further research and development efforts towards solid tumors. The company is accelerating our plans to identify a suitable strategic partner and will provide an update in due course.

Webcast on Updated Corporate Strategy

The company will host a live conference call and webcast on its updated strategy on Wednesday, November 16, 2022, at 3 pm CET. A Q&A session will follow management’s formal presentation. A new corporate deck providing an overview of Medigene’s technologies, pipeline, and strategic vision can now be found here: View Source

Following the call, an archived webcast will also be accessible on the Investor & Media section of the Medigene Web site View Source