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.

On October 16, 2023 OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE) reported the first Phase 1/2 positive clinical results with high affinity anti-PD1 monoclonal antibody OSE-279 in advanced solid tumors at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), held in Boston, MA (October 11 – 15, 2023 – Abstract number 35371, Poster C063) (Press release, OSE Immunotherapeutics, OCT 16, 2023, View Source [SID1234636046]).

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Silvia Comis, Head of Clinical Development and Regulatory Affairs of OSE Immunotherapeutics, comments: "These first efficacy and safety positive results from clinical Phase 1/2 assessing the therapeutic potential of our proprietary anti-PD1 monoclonal antibody OSE-279 in advanced solid tumors are very promising. These results encourage further clinical development of OSE-279 in the future as a monotherapy treatment in pre-identified cancer niche indications, with still high unmet medical needs. This product will also be available for combination with other OSE drug candidates or with external assets opening new potential partnerships."

The communication reported on the first positive results from the Phase 1/2 clinical trial evaluating OSE-279 monotherapy in patients with advanced solid tumors, with no therapeutic option available. These data have shown a manageable safety profile with preliminary signs of efficacy in the first 13 patients included with 8 tumor types and treated by a dose of 100 and 300 mg every 3 weeks (q3w) or 600 mg every 6 weeks (q6w). One confirmed partial response in a hepatocellular carcinoma patient (-81% tumor shrinkage) after a single dose of OSE-279 300 mg and 2 yet unconfirmed partial responses in anal squamous cell carcinoma (-46% tumor shrinkage) and undifferentiated pleomorphic sarcoma (-33% tumor shrinkage) with OSE-279 600 mg, were reported out of 11 patients with at least one post baseline tumor assessment. Furthermore, stable disease longer than 16 weeks was observed in 3 patients (Disease Control Rate: 55%). Pharmacokinetic profile showed good exposure and dose-proportionality and both pharmacokinetic and pharmacodynamic profiles were consistent with modelling. Receptor occupancy was maintained and within the boundaries of simulation. A Phase 2 dose (RP2D) of 300 mg was recommended every 3 weeks and 600 mg appears to be a good candidate for the RP2D every 6 weeks.

OSE-279 is a high affinity humanized anti-PD1 monoclonal antibody blocking both PD-L1 and PD-L2, the ligands of PD1 overexpressed by tumor cells and tumor microenvironment. OSE-279 is also the key anti-PD1 backbone component of OSE’s bifunctional checkpoint inhibitor BiCKI platform that is targeting PD1 and other new immune targets.

The first-in-human open label Phase 1/2 dose escalation and expansion study aims to determine the Maximum Tolerated Dose (MTD) and/or the RP2D of OSE-279 as a monotherapy in advanced solid tumors with two possible administration rates. Secondary objectives include assessment of OSE-279’s antitumor activity, evaluation of the safety profile, pharmacokinetic and receptor occupancy or pharmacodynamic profile (NCT05751798).