On October 16, 2023, ImmuneOnco Biopharmaceuticals (Shanghai) Co., Ltd. (referred to as "ImmuneOnco""the company’, Hong Kong Stock Exchange stock code: 01541.HK) reported that the company’s independently developed humanized IgG1 CD24 antibody(Project number: IMM47) was approved by the National Medical Products Administration (NMPA) for clinical trials (Press release, ImmuneOnco Biopharma, OCT 16, 2023, View Source [SID1234655694]). This is another milestone achievement in the rapid development of ImmuneOnco.

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IMM47 had also made a number of progresses previously by the efforts of the ImmuneOnco team. On September 27, the Australian phase I clinical trial of IMM47 successfully completed the enrollment of the first subject and officially entered the clinical research stage. The preclinical research results of the IMM47 project were published in "Antibody Therapeutics" on September 9. So far, IMM47 has obtained two authorized patents in China, and Japan, two pending patent applications in the United States and the European Union, and one pending patent application that may enter multiple approval of PCT patent of contracting countries in the future. In addition, we are ready to submit an IND application for IMM47 to the U.S. Food and Drug Administration (FDA) in near future.

CD24 is widely expressed in a variety of solid tumors including breast cancer, non-small cell lung cancer, colorectal cancer, hepatocellular carcinoma, renal cell carcinoma, ovarian cancer, and lymphoma, and is considered as an important marker of poor prognosis in these cancers which exhibits great clinical research potential.

With high specificity and high affinity to CD24 expressed on tumor cells, IMM47 can block immunosuppressive signals transmitted from the CD24/Siglec-10 pathway to macrophages, natural killer cells (NK) and T cells. By genetically engineered improved IgG1 Fc, IMM47 effectively activates macrophage and natural killer cell immune responses through powerful ADCP and ADCC. In preclinical animal in vivo efficacy studies, IMM47 showed to significantly increase the number of M1 macrophages in tumor tissues and downregulate CD24 expression in tumor cells, which also provide chances in combination with PD-1/PD-L1 immune checkpoint inhibitors and other drugs.

Dr. Tian, Wenzhi, founder and chairman of Immune Onco, said:" We are very pleased to see that our clinical trial application for IMM47, a humanized monoclonal antibody targeting CD24 for cancer treatment, was approved by the National Medical Products Administration (NMPA). The antibody screening for CD24 was quite challenging due to its small size of extracellular domain which exhibits weaker immunogenicity. We persevered through the accumulation of a lot of trivial work and finally got the IMM47 molecule with high affinity and specificity. With differentiated molecular design, IMM47 can specifically bind to CD24 and effectively activate macrophages and natural killer cell immune responses. Preclinical studies have shown that IMM47 has strong anti-tumor activity with great clinical development value. We will quickly advance the clinical trial of IMM47 to benefit more patients."

On October 16, 2023 SOTIO, a clinical-stage immuno-oncology company owned by PPF Group, reported a license and option agreement with Synaffix B.V., a Lonza company, to develop next-generation antibody-drug conjugates (ADCs) for the treatment of solid tumors (Press release, SOTIO, OCT 16, 2023, View Source [SID1234649863]). SOTIO will leverage Synaffix’s ADC technology platform to develop up to three novel ADCs targeting distinct tumor-associated antigens.

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"At SOTIO, we are building a broad pipeline of next-generation ADCs to address the challenges of solid tumors – and access to Synaffix’s ADC platform technologies will ensure we remain at the leading edge of this space," said Radek Spisek, M.D., Ph.D., chief executive officer of SOTIO. "This collaboration combining SOTIO’s deep expertise in solid tumor drug development with Synaffix’s clinical-stage platform technology will drive important new innovations for the benefit of patients."

The deal enables SOTIO to combine its proprietary antibodies with Synaffix’s ADC technology platform in order to deliver innovative new ADCs that can overcome the challenges of treating solid tumors. In addition to GlycoConnect and HydraSpace, the deal also includes Synaffix’s potent linker-payload platform including multiple different payloads.

"Synaffix’s ADC technology perfectly complements the technologies already in SOTIO’s ADC platform, including the iADC technology licensed from NBE-Therapeutics and the ConjuALL technology licensed from LegoChem," said Martin Steegmaier, chief scientific officer of SOTIO. "The addition of Synaffix’s capabilities will greatly expand our ability to select and tailor the most suitable ADC technology and payload for the needs of a particular target and particular solid tumor indication."

Under the terms of the agreement, Synaffix is eligible to receive upfront and potential milestone payments worth up to $740 million, plus single-digit royalties on net sales. SOTIO will be responsible for research, development, manufacturing and commercialization of the ADC products, while Synaffix will closely support SOTIO’s research activities and be responsible for the manufacturing of components that are specifically related to its proprietary GlycoConnect, HydraSpace, and linker-payload technologies.

Peter van de Sande, head of Synaffix, added, "The selection of our ADC technologies by a seasoned ADC player like SOTIO is a strong recognition of the potential of these technologies to maximize the therapeutic index of ADCs. We look forward to partnering with SOTIO, and believe that with their singular focus on cancer immunotherapies and robust clinical pipeline, this partnership can deliver innovative medicines for patients in areas of high unmet medical need."

SOTIO is advancing a pipeline of novel ADCs tailored to address the treatment needs of specific solid tumor types. SOT102, the company’s most advanced ADC program, is a CLDN18.2-targeting ADC in Phase 1/2 development for the treatment of gastric, pancreatic and other cancers that have very few targeted treatment options available. The company is progressing dose-finding studies in the trial’s monotherapy arm, with SOT102 as a later-stage treatment, and recently announced the initiation of the trial’s combination therapy arm in first-line treatment of gastric and pancreatic cancer patients. SOTIO additionally has two other ADC programs in preclinical development.

On October 16, 2023 Theralase reported an update to its Phase II Bacillus Calmette Guérin ("BCG")-Unresponsive Non-Muscle Invasive Bladder Cancer ("NMIBC") Carcinoma In-Situ ("CIS") (with or without resected Ta / T1 papillary disease) clinical study ("Study II") (Press release, Theralase, OCT 16, 2023, View Source [SID1234636147]).

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To date, Theralase has enrolled and provided the primary Study II Treatment for 62 patients.

The Study II Endpoints have been defined as:

Primary: Efficacy – Defined as Complete Response ("CR") rate at any point in time (CR is defined as at least one of the following:

Negative cystoscopy and negative (including atypical) urine cytology
Positive cystoscopy with biopsy-proven benign or low-grade NMIBC and negative cytology
Negative cystoscopy with malignant urine cytology, if urothelial cancer is suspected in the upper tract or prostatic urethra and random bladder biopsies are negative)
Secondary: Duration of CR – Defined as 12 months post initial CR assessment

Tertiary: Safety – Defined as the incidence and severity of Adverse Events ("AEs"), Grade 4 or higher, directly related to the Study Drug or Study Device, that do not resolve within 450 days post primary Study II Treatment; whereby: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening or disabling, Grade 5 = Death.

In addition, survival surveillance for all patients, who achieve a CR or Indeterminate Response ("IR") (negative cystoscopy and positive urine cytology, without confirmatory negative bladder cancer biopsies) at 450 days and remain in Study II will be monitored past 450 days.

In performance to the primary, secondary and tertiary endpoints, refer to the clinical data below.

Achieved Primary Objective (n) Achieved Primary Objective (%) Achieved Secondary Objective (n) Achieved Secondary Objective (%) Achieved Tertiary Objective (n) Achieved Tertiary Objective (%)
Complete Response ("CR") 37 65% 14 33% 57 100%
Indeterminate Response ("IR") 5 9% 2 5% 0 0%
Total Response (CR and IR) 42 74% 16 38% 57 100%
Evaluable Patients 57 42 57

Note: Evaluable patients are defined as patients who have been assessed by a principal investigator during a particular assessment visit.

The CR, IR and Total Responders are detailed below by assessment visit.

TLD 1433-2 Clinical Study (Evaluable Patients)
Assessment 90 Day 90 Day 180 Day 180 Day 270 Day 270 Day 360 Day 360 Day 450 Day 450 Day
# % # % # % # % # %
Complete Response ("CR") 33 58% 31 56% 23 46% 16 36% 14 33%
Indeterminate Response ("IR") 4 7% 8 15% 6 12% 2 4% 2 5%
Total Responders (CR and IR) 37 65% 39 71% 29 58% 18 40% 16 38%
Total Evaluated 57 55 50 45 42

On August 1, 2020, the Company optimized the Study II Treatment. For patients that received the optimized Study II Treatment the CR, IR and Total Responders are detailed below by assessment visit.

TLD 1433-2 Clinical Study (Evaluable Patients) (Optimized: Post August 1, 2020)
Assessment 90 Day 90 Day 180 Day 180 Day 270 Day 270 Day 360 Day 360 Day 450 Day 450 Day
# % # % # % # % # %
Complete Response ("CR") 29 64% 28 62% 20 50% 13 37% 11 34%
Indeterminate Response ("IR") 3 7% 7 16% 5 13% 2 6% 2 6%
Total Responders (CR and IR) 32 71% 35 78% 25 63% 15 43% 13 41%
Total Evaluated 45 45 40 35 32

Theralase is currently working with its clinical study sites in Canada and the United States to compile information requested by the Food and Drug Administration ("FDA") for re-submission of a pre-Break Through Designation ("BTD").

If the pre-BTD submission is successful, this could lead to BTD approval.

Arkady Mandel, MD, PhD, DSc, Chief Scientific Officer of Theralase stated, "Theralase is delighted in its latest clinical data analysis. The Theralase RuvidarTM-based Anti-Cancer Therapy ("ACT") has shown remarkable single-agent activity by proving to be safe and effective on a very difficult to treat BCG-Unresponsive patient population that has been diagnosed with high-grade NMIBC CIS, with or without resected Ta / T1 papillary tumours. These patients have failed the standard of care, such as BCG therapy and a large majority of them have failed treatment with various modern immunotherapy drugs. Theralase has been able to demonstrate strong efficacy in the form of a CR or IR, with a well-tolerated safety profile, after predominately one treatment. This ACT technology, pending successful regulatory approval and commercialization, will be very attractive to patients, uro-oncologists and the insurance companies that insure these patients."

Mr. Roger DuMoulin-White, BSc, P.Eng, Pro.Dir, President and Chief Executive Officer of Theralase stated, "To date, the Theralase Study II clinical data has demonstrated best-in-class performance for a single agent, providing high efficacy, durable response and a high safety profile, with no serious adverse events directly related to RuvidarTM or the TLC-3200 Medical Laser System. Theralase hopes to complete patient enrollment with accompanying administration of the primary Study II Treatment by year end 2024. If successful, this will allow the Company the ability to complete assessment of the primary, secondary and tertiary endpoints of these patients by 2026. Based on the clinical data to date, Theralase is investigating potential partnerships for commercialization, financing and distribution of this ACT technology on an international basis. Theralase looks forward to commercializing this world-class technology for the benefit of all shareholders."

On October 16, 2023 Incendia Therapeutics, formerly Parthenon Therapeutics, a precision oncology company discovering and developing a novel class of therapies that reprogram the tumor microenvironment (TME), reported that it will have two poster presentations at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023, to be held in Madrid, Spain October 20-24, 2023 (Press release, Incendia Therapeutics, OCT 16, 2023, View Source [SID1234636048]).

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The company will present data on the expression of discoidin domain receptor 1 (DDR1) mRNA and protein across 20 tumor types and will provide a detailed overview of Incendia’s Phase 1 first-in-human clinical trial for its lead candidate PRTH-101 in patients with advanced solid tumors (NCT05753722).

"The tumor microenvironment is dramatically impacted by the over expression of DDR1 and its role in the alignment of collagen fibers, which ultimately prevents immune cells from being able to directly interact with tumors," said Laura Dillon, Vice President of Translational Medicine and Bioinformatics at Incendia. "These data presented at ESMO (Free ESMO Whitepaper) further highlight the potential of PRTH-101 as a first-in-class DDR1 inhibitor that may address the unmet need in the numerous cancers with high DDR1 expression."

Presentation Details:
Title: High DDR1 mRNA and Protein Expression Across Human Tumor Types Correlate with Epithelial Composition of the Tumor Microenvironment
Lead author: Laura Dillon, Ph.D., Vice President, Translational Medicine and Bioinformatics at Incendia Therapeutics
Presentation #: 2309P
Presentation Time: Saturday, October 21, 12:00 – 1:00 PM CEST (6-7 AM ET) Translational Research (agnostic)

Key Highlights:

DDR1 is expressed in a high proportion of tumor cells across a range of epithelial tumor types, suggesting potentially broad application of DDR1-targeted therapies. A high proportion of tumor cells (median of 0.76) expressed DDR1 across all epithelial tumor types. DDR1 expression was uniformly low in mesenchymal tumors (median of 9 cells/mm2) compared to epithelial tumors (median of 2803 cells/mm2). Moderate correlation was observed between DDR1 mRNA expression and DDR1+ cell density across tumor types (R=0.48, p<0.0001). In epithelial tumors, both DDR1 mRNA and protein expression were correlated with the percentage of epithelium (R=0.37 and 0.56, respectively; both p<0.0001), with significant variance between tumor types.

Title: A Phase 1 First-in-Human Study of PRTH-101, an IgG1 Monoclonal Antibody Targeting DDR1, as a Monotherapy and Combined with Pembrolizumab in Patients with Advanced Solid Malignancies
Lead author: Shiraj Sen, M.D., Ph.D., Medical Oncologist and Director of NEXT Oncology Dallas
Presentation #: 1079TiP
Presentation Time: Monday, October 23, 12:00 – 1:00 PM CEST (6-7 AM ET) (Investigational immunotherapy)

Key Highlights:

Discoidin domain receptor 1 (DDR1) is a collagen receptor that represents a promising therapeutic target due to its role in excluding lymphocytes from the tumor microenvironment (TME) by aligning collagen fibers. DDR1 expression is high in multiple cancer types and associated with worse survival. PRTH-101 is a humanized IgG1 antibody that binds to the extracellular domain of both membrane-bound and soluble DDR1. In preclinical models, PRTH-101 monotherapy resulted in disruption of aligned collagen fibers in the tumor stroma, increased infiltration of lymphocytes, and tumor growth inhibition. When PRTH-101 is combined with PD-1 inhibition, activated T cell infiltration is increased compared to PRTH-101 alone.

This is a Phase 1 first-in-human study that will evaluate intravenous PRTH-101 +/- pembrolizumab in patients with advanced solid tumors. Safety, efficacy, pharmacokinetic, and pharmacodynamic endpoints will be monitored and reported.
The first part of the study (Ph1a) seeks to identify the maximum tolerated dose (MTD) or optimal biologic dose (OBD), of PRTH-101 to determine the recommended phase 2 dose (RP2D).
The second part (Ph1b) seeks to identify the MTD or OBD of PRTH-101 in combination with pembrolizumab to determine the PRTH-101 combination RP2D.
The third part (Ph1c) consists of dose expansion in disease-directed cohorts to assess the anti-tumor efficacy of PRTH-101 monotherapy and/or combination therapy.
About PRTH-101

PRTH-101 is a therapeutic antibody that specifically binds to and blocks discoidin domain receptor 1 (DDR1,) a protein expressed on tumor cells that binds collagen to make a physical barrier that prevents immune cells from interacting with and attacking tumor cells. By disabling DDR1, the collagen fibers lose alignment and loosen, creating gaps in the tumor barrier, thus allowing T-cells to enter and attack the tumor. Blockade of DDR1 represents a unique approach to stimulating immune-based antitumor activity, and in preclinical models such blockade shows both single agent anti-tumor activity as well as marked augmentation of immunity enhanced by PD-1 blockade. Tumor types that express high levels of DDR1-associated collagen barriers include colorectal, ovarian, and non-small cell lung cancer. Currently, there are no approved drugs that target DDR1.

On October 16, 2023 TME Pharma N.V. (Euronext Growth Paris: ALTME), a biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported that the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) has published an abstract on the ongoing NOX-A12 GLORIA Phase 1/2 trial in first-line brain cancer (glioblastoma) (Press release, TME Pharma, OCT 16, 2023, View Source [SID1234636047]). The data will be presented in an oral presentation at the ESMO (Free ESMO Whitepaper) Congress by Dr. Julian Layer, one of the investigators of the GLORIA trial, on Saturday, October 21, 2023, starting at 11:15 a.m. CEST in Madrid, Spain.

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The abstract highlights an in-depth analysis of how the combination of radiotherapy and the CXCL12 inhibitor NOX-A12 remodels the immune tumor microenvironment in newly diagnosed glioblastoma. Results from matched pre- and post-treatment analysis of tumor tissue from the GLORIA trial support the modes of action of treatment with radiotherapy and NOX-A12 (1) to counteract vasculogenesis, i.e. the de novo creation of blood vessels from bone marrow-derived cells after radiotherapy, and (2) to modulate the tumor immune microenvironment leading to proliferation and clustering of cytotoxic T cells in tumor tissue.

Details of the oral presentation at the ESMO (Free ESMO Whitepaper) Congress 2023 are as follows:

Title: Spatial remodeling of the immune tumor microenvironment after radiotherapy of CXCL12 inhibition in glioblastoma in the Phase 1/2 GLORIA trial
Speaker: Dr. Julian Layer, University of Bonn, Germany
Session: Mini Oral 508MO
Lecture Time and Date: 11:15-11:20 a.m. CEST, Saturday, October 21, 2023

The full abstract is available online via the ESMO (Free ESMO Whitepaper) Congress website and the TME Pharma website. TME Pharma will also publish the full presentation on its website at the time of the lecture on October 21.