On March 14, 2023 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported the initiation of AIPAC-003 (Active Immunotherapy, Eftilagimod Alpha, and PAClitaxel), an integrated Phase II/III trial to evaluate eftilagimod alpha ("efti") in combination with paclitaxel for the treatment of metastatic HER2-neg/low breast cancer (MBC) (Press release, Immutep, MAR 14, 2023, View Source [SID1234628600]). Regulatory approval has been received in the US and Institutional Review Board (IRB) approval has been received in Spain, with approvals in additional countries anticipated to follow shortly. The first patient is expected to be enrolled in early Q2 CY2023.

As a first-in-class soluble LAG-3 protein targeting MHC Class II ligands on antigen-presenting cells (APC), efti is uniquely positioned to improve clinical outcomes from standard-of-care chemotherapy. Its activation of APCs (e.g., dendritic cells, monocytes) triggers a broad immune response that includes significant increases in cytotoxic CD8+ T cells armed with chemo-induced tumour antigens to target cancer. This synergy was demonstrated by the AIPAC Phase IIb trial’s encouraging efficacy and safety, including a +2.9-month median overall survival (mOS) improvement, statistically significant mOS improvements between 4.2 to 19.6 months across three pre-specified subgroups, a statistically significant increase in cytotoxic CD8 T cells that correlated with improved OS, a higher 48% ORR (vs 38% for chemo alone), and a superior Quality of Life preservation.

Immutep CEO, Marc Voigt, said: "With its novel mechanism of action to activate antigen-presenting cells, efti has to date safely improved clinical outcomes from anti-PD-(L)1 therapies and standard-of-care chemotherapy. We look forward to AIPAC-003 building upon the encouraging synergy seen in our previous Phase IIb trial in metastatic breast cancer, especially with its three key adaptations: same day administration of efti plus paclitaxel, this dual IO-chemotherapy treatment continuing until disease progression, and a new primary endpoint of overall survival. The selected Phase II/III trial design allows us to move forward with a risk-balanced approach in MBC, as we continue our prioritized late-stage clinical development with anti-PD1 therapy in 1st line head & neck squamous cell carcinoma and 1st line non-small cell lung cancer."

The Company and the US Food and Drug Administration (FDA) agreed to the integrated Phase II/III trial design for AIPAC-003 that will help inform a Biologics License Application (BLA). Additionally, the trial design incorporates feedback from Scientific Advice meetings with the European Medicines Agency (EMA) to support a Marketing Authorisation Application (MAA).

Based on feedback from the FDA/EMA, the HR+/HER2-neg/low MBC patient population has been expanded to include triple-negative breast cancer (TNBC), an aggressive cancer with limited treatment options, which together account for ~78% of breast cancer cases. The Company and the FDA also agreed to an open-label lead-in component of 6 to 12 patients to test 90mg efti dosing in combination with paclitaxel driven by efti’s excellent safety profile, along with the FDA’s Project Optimus initiative in oncology. Additionally, patients will receive same-day administration of efti + paclitaxel that can continue until disease progression, unlike the prior AIPAC trial that administered both on different days and stopped chemotherapy at six months.

The open-label lead-in of up to 12 patients will be followed by a randomized (1:1) portion of the Phase II consisting of up to 58 patients that will receive 30mg efti or 90mg efti to determine the optimal biological dose in combination with paclitaxel. Depending on the Phase II results, potential regulatory actions and resources, a randomized, double-blinded, placebo-controlled Phase III portion will then follow. The Phase III will have overall survival as the primary objective and may include a specific patient population.

With respect to the late-stage clinical development of efti, the Phase II portion of the MBC trial, the ongoing randomized/controlled Phase II trial in 1st line HNSCC, and the initiation of the registrational trial in 1st line NSCLC are included in the budget and have no impact on the Company’s expected cash runway to the end of the 1st half of calendar year 2024.

About Eftilagimod Alpha (Efti)
Efti is Immutep’s proprietary soluble LAG-3 clinical stage candidate that is a first-in-class antigen-presenting cell (APC) activator that stimulates both innate and adaptive immunity for the treatment of cancer. Efti binds to and activates antigen presenting cells via MHC II molecules leading to expansion and proliferation of CD8+ (cytotoxic) T cells, CD4+ (helper) T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer.

Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and HER2–/HR+ metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track Designation in 1st line HNSCC and in 1st line NSCLC from the United States Food and Drug Administration (FDA).

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On March 13, 2023 ITM Isotope Technologies Munich SE (ITM), a leading radiopharmaceutical biotech company, Helmholtz Munich and the Departments of Neurosurgery and Nuclear Medicine at the University Hospital Münster reported the start of a Phase I clinical trial with ITM’s drug candidate ITM-31 (formerly LuCaFab), a novel Targeted Radionuclide Therapy candidate for the treatment of malignant glioblastoma. ITM-31 is a carbonic anhydrase (CA) XII-specific antibody Fab fragment developed by Helmholtz Munich coupled with ITM’s medical radioisotope, non-carrier-added lutetium-177 (n.c.a 177Lu, EndolucinBeta). The investigator-initiated trial (IIT) is sponsored by the University Hospital Münster, conducted in hospitals in Münster, Essen, Cologne, Würzburg, and supported by ITM and Helmholtz Munich. Patient recruitment for the study is ongoing.

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Glioblastoma is a malignant brain tumor with a median survival of approximately 14 to 15 months from diagnosis.1 After treatment with standard therapies (surgery, radio- and chemotherapy), there is a risk that individual tumor cells will remain in the tissue and begin to grow again (relapse). Therefore, treatment of tissue surrounding the tumor is of great importance. ITM-31 has been designed specifically to target residual tumor cells in this surrounding tissue, with the aim of mitigating tumor recurrence.

"A treatment capable of selectively eliminating dormant residual tumor cells after surgical removal of glioblastoma and standard radiochemotherapy gives hope for greater success than with the current standard therapy alone. Intracavitary Radionuclide Therapy with ITM-31 could provide such a treatment opportunity," says Prof. Walter Stummer, Principal Investigator and Chairman of the Department of Neurosurgery at the University Hospital Münster. Study Coordinator Prof. Hans-Jürgen Reulen adds: "Initial compassionate use with ITM-31 (LuCaFab) and previous studies with other radiotherapeutic drug candidates have shown promising results and support the potential of the radiotherapeutic approach for this hard-to-treat cancer type."

The Targeted Radionuclide Therapy candidate ITM-31 targets a specific protein (antigen) called CA XII, which is highly expressed on the cell surface of glioblastoma cells, but not found on healthy brain cells. It comprises a CA XII antibody Fab fragment coupled with the radioisotope 177Lu. ITM-31 is administered directly into the tumor cavity from where it migrates into the surrounding tissue with high specificity, binding to glioblastoma cells which are then irradiated and potentially destroyed while healthy tissue is spared. ITM-31 could thus act as a complementary, adjuvant therapy to the current standard of care approach as it is designed to be applied after initial treatment to glioblastoma to prevent future tumor growth.

"Several published preclinical studies, including ones by our research group, report significant success in the field of Targeted Radionuclide Therapy for brain tumors," comments Prof. Reinhard Zeidler, Project Leader at Helmholtz Munich. "ITM-31, unlike other radionuclide therapies, applies a ‘downsized antibody’, a so-called Fab fragment, which spreads throughout the tissue more easily. Such improved pharmaceutical properties have the potential to create further benefits for the treatment of seriously ill patients living with cancer."

"Together with our partners, our goal is to develop an effective and safe therapeutic option for patients living with this malignant brain tumor," says Steffen Schuster, CEO of ITM. "ITM-31 is a novel treatment approach that is targeted to the cancer cells that evade current treatment regimens, causing glioblastoma to be one of the most aggressive and difficult to treat cancers. This trial is an important first clinical step to developing ITM-31 into a drug potentially capable of circumventing previous hurdles in this high-need indication."

About the Phase I clinical trial with ITM-31
The aim of the dose-escalation study (NCT05533242) with up to 15 patients is to collect data on the efficacy, tolerability, and safety of the investigational drug and to evaluate the best possible patient dose for future studies. Before being treated with ITM-31 in the trial, patients undergo 6 months of standard radio-chemotherapy treatment after surgery. Three single doses of the investigational drug are administered over three months.

(Press release, ITM Isotopen Technologien Munchen, MAR 13, 2023, View Source,_Helmholtz_Munich_and_University_Hospital_M%C3%BCnster_Announce_Start_of_Phase_I_Clinical_Trial_with_Radiotherapeutic_ITM-31_for_Glioblastoma-605/ [SID1234661154])

On March 13, 2023 Patrys reported that a new preclinical study exploiting the novel ability of deoxymabs to enter the cell nucleus to disrupt the cell’s DNA Damage Response (DDR) systems, has validated the potential use of Patrys’ full-sized IgG antibody, PAT-DX3, for synthetic lethality strategies to treat relevant cancers (Press release, Patrys, MAR 13, 2023, View Source [SID1234628683]).

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‘Synthetic lethality’ is a treatment strategy which involves targeting a specific genetic mutation or pathway that is essential for tumour cell survival. In tumours with pre-existing mutations that compromise DDR systems – such as BRCA2 negative breast cancer – adding a deoxymab could make it susceptible to the accumulation of DNA damage, causing tumour cell death.

Patrys’ CEO and Managing Director, Dr James Campbell said:

"This study, requested by a potential partner as part of Patrys’ ongoing business development activities, confirms the potential to use deoxymabs as a single agent to treat cancers which have pre-existing mutations that compromise their DDR systems, including BRCA2 negative breast cancer and other cancers. In addition, Patrys is looking at using deoxymabs in combination with DNA damaging therapies, such as radiation and chemotherapies, and as a delivery agent for small molecules and nucleic acids."

On March 13, 2023 Portage Biotech presenting its corporate presentation (Presentation, Portage Biotech, MAR 13, 2023, View Source [SID1234628657]).

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On March 13, 2023 Shennon Biotechnologies ("ShennonBio"), a biotech company using a proprietary single cell platform to create more effective immunotherapies, reported the close of a $13M oversubscribed seed financing round led by DCVC, with participation from Foundation Capital, AV8 and angel investors (Press release, Shennon Biotechnologies, MAR 13, 2023, View Source [SID1234628617]).

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Founded in 2021, ShennonBio has developed a proprietary platform that can profile millions of immune cells functionally at the single cell level within a few hours, enabling the identification of TCR or antibody targets to develop more precise and effective immunotherapies. In the last 1.5 years, ShennonBio has demonstrated the power of its platform by identifying rare, functionally activated T cells and establishing collaborations with multiple clinical centers to study patient samples. The recent funding will be used to further expand the capabilities of the platform and scale discovery efforts to build a pipeline of effective targets for solid tumors.

A key step in developing effective cancer immunotherapies is to find the right target effector immune cell, to expand or create them on a massive scale outside of the body before reinfusing them back into the body to mimic a strong natural immune response. However, identifying cancer antigen specific immune cells is very difficult. Due to the enormous diversity of immune cells, searching for the right T cell or B cell that can recognize cancer antigens and effectively attack cancer cells is like searching for a needle in a haystack. A lot of effort has been made to figure out how to profile such a diverse population and isolate the rare effective immune cells for cancer immunotherapy. However, most current technologies developed cannot functionally profile such a massive number of cells at the single cell level, and it often takes weeks, if not months to isolate a relevant target.

ShennonBio’s technology resolves the current bottleneck in immunotherapy target discovery, as it enables functional profiling of immune cells at the single cell level at unprecedented throughput, enabling target identification and selection within a day – instead of weeks or months.

"At ShennonBio, our interdisciplinary team of engineers and scientists have developed a single-cell screening platform that can identify rare effector T cells against specific antigens at ultrahigh throughput by measuring functional secretion," said Li Sun, Ph.D., CEO & Founder, Shennon Biotechnologies. "While current approaches take weeks to isolate a T cell target, our technology platform can do this in a matter of hours, with more precision, which ultimately increases the overall probability of generating a curative treatment in a shorter period of time for cancer patients. We’re thrilled to have the support of such a great group of investors and be able to scale up our target discovery efforts with this funding."

"ShennonBio is revolutionizing the field of immunotherapy with their proprietary single-cell platform that can analyze immune cells and their interactions with antigens with unprecedented accuracy and efficiency. This technology has the potential to overcome a key bottleneck in immunotherapy by identifying rare antigen-specific immune cells through enabling high-throughput analysis of functional pairing between effector and target cells in a way that was previously impossible," said Dr. Joseph Fraietta, Director of the Solid Tumor Immunotherapy Lab at the University of Pennsylvania, and a scientific advisor for the company.

"Li is leading a company with a bold vision to revolutionize the field of immunotherapy. Her team’s expertise and unwavering dedication to creating better target pipelines for immunotherapies is nothing short of impressive," said James Hardiman, Partner, DCVC. "We believe that ShennonBio’s innovative approach has the potential to make a significant impact in the industry, and we are proud to support them in this mission."

"From the first time we met Li, we have been very impressed with her passion and vision for building a company that addresses existing bottlenecks in developing effective immunotherapies," said Ruchita Sinha, General Partner, AV8. "Shennon’s proprietary platform provides a powerful and ultra high throughput way to profile immune cell interactions at a single cell level. We firmly believe that the company’s platform will enable better development of T cell therapies not only for Shennon, but also for the broader ecosystem."

ShennonBio is actively expanding the team and welcomes candidates who are passionate about making an impact in developing novel cancer therapies to apply through their website.