On March 13, 2025 SOTIO Biotech, a clinical-stage biopharmaceutical company owned by PPF Group, reported it will be exercising its option, under its license and option agreement with Synaffix B.V. ("Synaffix"), a Lonza company (SWX: LONN), to obtain a license to Synaffix’s technology to develop two bispecific antibody-drug conjugate (ADC) programs (Press release, SOTIO, MAR 13, 2025, View Source [SID1234651142]).

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The exercised option will enable SOTIO to advance two bispecific candidates, designed by its in-house research team, that have the potential to become first-in-class and/or best-in-class treatments for solid tumors. SOT112 is a bispecific ADC with potential applicability in several major cancer indications, while SOT113 demonstrates promise for precision targeting of prostate cancer. Both programs leverage the selection of highly attractive target pairs and are now in the lead nomination stage.

The bispecific antibody candidates were identified by SOTIO’s research team and will now be developed under SOTIO’s license and option agreement with Synaffix, which enables SOTIO to combine its proprietary antibodies with Synaffix’s GlycoConnect, HydraSpace, and potent linker-payloads of the toxSYN platform to research, develop, manufacture, and commercialize ADC products.

"The promising preclinical data on SOT112 and SOT113 have reinforced our confidence in their potential, and we are excited to advance these candidates within our first-in-class and best-in-class ADC portfolio," said Martin Steegmaier, Ph.D., chief scientific officer of SOTIO. "Bispecific ADCs represent a groundbreaking frontier in oncology, offering enhanced tumor-targeting precision and the potential to overcome the challenges of heterogeneity in solid tumor target expression. Both advancements align with our mission to develop safer and more effective treatments for solid tumors."

Peter van de Sande, head of Synaffix, commented: "We are pleased that SOTIO, recognizing the versatility and robustness of our clinically validated platform, has chosen to expand its use of our ADC technology to two additional targets. ADCs are a key part of our offering, and our technology is primed to support this next stage of innovation in targeted cancer therapeutics. We look forward to seeing these promising candidates advance toward the clinic."

Under the terms of the agreement, Synaffix is eligible to receive an upfront payment with the potential for milestone payments, plus single-digit royalties on net sales. SOTIO will be responsible for research, development, manufacturing, and commercialization of the ADC products, and 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-payloads of the toxSYN technologies.

On March 13, 2025 BioCity Biopharmaceutics Co., Ltd., a clinical-stage biopharmaceutical company, reported that it has entered into a clinical trial collaboration agreement with MSD (Merck & Co., Inc., Rahway, NJ, USA), to evaluate the combination of BioCity’s BC3195 and MSD’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in a global phase 1/2 trial in patients with locally advanced or metastatic solid tumors (Press release, Biocity Biopharmaceutics, MAR 13, 2025, View Source [SID1234651141]).

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Under the terms of the agreement, BioCity will conduct a phase 1/2 clinical trial to evaluate the safety and efficacy of BC3195 in combination with KEYTRUDA. BioCity and MSD each retain all commercial rights to their respective compounds. The recruitment in the clinical study is expected in Q4 2025.

"We are encouraged by the clinical data we have seen thus far for BC3195 as monotherapy, which have demonstrated improved anti-tumour activity in patients with certain non-small cell lung and breast cancers. We now look forward to exploring the potential of BC3195 in combination with KEYTRUDA through this collaboration, as we continue to advance our clinical program and seek to further validate our differentiated drug discovery and development approach." Said by Ivy Wang, Co-founder and Executive President of BioCity.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About BC3195

BC3195 is currently the only ADC targeting CDH3 (P-Cadherin) in clinical development globally. In preclinical studies, BC3195 binds to membrane CDH3 with strong affinity and is efficiently internalized. BC3195 is designed with a clinically validated, cleavable linker and payload (vc-MMAE) allowing for the destruction of targeted cancer cells, as well as surrounding cells, which is known as the bystander effect. In animal models, BC3195 demonstrated a favorable safety profile and robust antitumor activity with tumor growth inhibition ≥100% in some animals bearing well established cancers.

BC3195 is currently undergoing concurrent Phase I dose optimization and dose expansion in China and in US. BC3195 demonstrated a manageable safety profile and favorable PK characteristics, significant antitumor activity with confirmed PRs observed across multiple tumor types.

On March 13, 2025 Third Arc Bio Inc., a clinical stage biotech company developing novel multifunctional antibodies for a range of oncology and immunology & inflammation (I&I) indications, reported the first patient has been dosed in its first-in-human study evaluating ARC101, a potential best-in-class T cell engager targeting Claudin 6 (CLDN6) (Press release, Third Arc Bio, MAR 13, 2025, View Source [SID1234651140]).

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This Phase 1 study will evaluate the optimal dosing, safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary antitumor efficacy of ARC101 as monotherapy in patients with locally advanced or metastatic solid tumors expressing CLDN6.

"ARC101 is the first program from our growing pipeline to reach the clinic – signifying Third Arc Bio’s transition into a clinical stage company," said Peter F. Lebowitz, MD, PhD, Chief Executive Officer and Chief Medical Officer of Third Arc Bio. "Given ARC101’s remarkable specificity for CLDN6 over other Claudin proteins, we believe ARC101 has the potential to achieve a superior therapeutic index in the clinic. As we advance the ARC101 clinical program, we are also rapidly progressing our next programs towards the clinic with the execution of critical IND-enabling studies."

ARC101 represents the company’s first clinical effort to evaluate in humans its immune cell engaging antibodies that modulate the immune system in precise ways to target specific disease states. Building upon ARC101 as a foundation, Third Arc Bio continues to invest in its Synergy Platform to develop a pipeline of novel CD3 and CD28 targeting multispecifics to create transformational drugs against solid tumors.

Third Arc Bio will present a poster highlighting preclinical results for ARC101 at the upcoming 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. The data will highlight ARC101’s best-in-class specificity for CLDN6 versus other closely related Claudin proteins.

On March 13, 2025 TransCode Therapeutics, Inc. (NASDAQ: RNAZ), the RNA oncology company committed to more effectively treating cancer using RNA therapeutics, reported that the Safety Review Committee (SRC) monitoring its Phase I clinical trial has unanimously approved opening of the fourth cohort of patients based on the SRC’s favorable review of Cohort 3 safety data (Press release, TransCode Therapeutics, MAR 13, 2025, View Source [SID1234651139]). The therapeutic candidate being evaluated, TTX-MC138, is a first-in-class therapeutic designed to treat multiple metastatic cancers using antisense technology. The dose administered to the fourth cohort, as originally planned in the clinical protocol, will be approximately fifty percent higher than the dose administered in the third cohort.

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Under the clinical protocol, patients may remain on study absent safety events or disease progression. Out of 9 patients treated with TTX-MC138 in the first three cohorts, 6 remain on study for continued treatment since there have been no dose limiting toxicities or disease progression with these patients. The patient that has remained on study the longest has, to date, received 7 doses each approximately 28 days apart over the approximately 7 months that this patient has been on study. In addition to approving opening the fourth cohort, the SRC approved enrollment of additional patients in Cohort 3 to build upon the safety profile of TTX-MC138. Further, Cohort 1 and 2 data analysis for both pharmacokinetic (PK) and pharmacodynamic (PD) activity is ongoing and suggests that TTX-MC138 demonstrates a PK/PD profile consistent with preclinical results and results from TransCode’s Phase 0 clinical trial. Preliminary results from Cohort 2 confirmed observations from the Phase 0 trial and from Cohort 1 that the drug candidate shows evidence of activity in patient blood. Preliminary PK analysis suggests that dose levels 0.8-1.6 mg/kg, the levels administered to Cohorts 1 and 2, could represent an efficacious range.

"SRC approval to open the fourth cohort and expand enrollment in Cohort 3 is an important advancement for the clinical trial. It will provide an opportunity to obtain additional safety and PK/PD data, inform the dose expansion stage of the clinical trial and may allow us to obtain initial evidence of clinical activity" commented Sue Duggan, TransCode’s Senior Vice President of Operations. Duggan added, "Enrollment into the study continues based on the cumulative safety data review. Eligible subjects may now be screened and scheduled in Cohort 4 for treatment with the next dose level of TTX-MC138 while preliminary data analysis continues."

About TTX-MC138

TTX-MC138 is a first-in-class therapeutic candidate that targets microRNA-10b, a micro-RNA widely believed to be a driver of metastatic disease. TransCode’s 2023 Phase 0 clinical trial produced evidence of delivery of a radiolabeled version of TTX-MC138 to metastatic lesions and pharmacodynamic activity, even at a microdose of the drug candidate, suggesting a broad therapeutic window for TTX-MC138.

About the Trial

TransCode’s Phase 1 clinical trial is a multicenter, open-label, dose-escalation and dose-expansion study, designed to generate critical data to support evaluation of the safety and tolerability of TTX-MC138 in patients with a variety of metastatic solid cancers. While not an endpoint, the trial may provide early evidence of clinical activity of TTX-MC138. The trial comprises an initial dose-escalation stage followed by a dose-expansion stage. The primary objective of the dose-escalation stage is to evaluate the safety and tolerability of escalating dose levels of TTX-MC138. In the dose-expansion stage, the safety, tolerability and anti-tumor activity of TTX-MC138 will be further evaluated in certain tumor types selected based on preliminary results from the dose-escalation stage.

Further information is available at www.clinicaltrials.gov NCT Identifier: (NCT06260774).

On March 13, 2025 Blue Earth Therapeutics reported further promising developments for its radiohybrid lutetium labelled, PSMA targeted, investigational radioligand therapy (Press release, Blue Earth Therapeutics, MAR 13, 2025, View Source [SID1234651138]). Radiation dosimetry and pharmacokinetic data from the 13 metastatic castrate resistant prostate cancer patients enrolled in the Phase 1 portion of a Phase 1/2 clinical trial (NCT05413850) of Lutetium (177Lu) rhPSMA-10.1 Injection showed proportionately higher absorbed radiation doses in tumours than in critical healthy tissues such as the kidneys. The data compares favourably to published data on first-generation PSMA-targeted radioligand therapies.1,2

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The Phase 1 data shows that Lutetium (177Lu) rhPSMA-10.1 Injection has high ratios for absorbed radiation dose to tumours vs. dose to healthy tissues, with a measured mean tumour to salivary gland ratio of 73 and tumour to kidney ratio of 32. Median absorbed radiation dose to tumours defined by SPECT imaging was 8.9 Gy for each GBq of administered radioactivity. Mean absorbed radiation dose to the kidneys was 0.27 Gy/GBq; to salivary glands, 0.13Gy/GBq.

Underlying these results, the mean biological half-life in tumors for the Lutetium (177Lu) rhPSMA-10.1 Injection was 338 hours. When paired with the 6.7-day physical half-life of 177Lu, this gives an effective mean half-life of 91.4 hours. This allows delivery of radiation to tumors over many days: one and a half to twice the reported data for established agents in this class1. This prolonged retention of the drug in tumors without proportionate increases to retention in normal tissues helps to explain the positive radiation dosimetry data.

Following recent consultation with regulatory authorities, and sharing of the preliminary data, this now opens the way for the Phase 2 portion of the Phase 1/2 trial to test innovative dosing regimens, with the goal of optimising outcomes for patients. This Phase 2 portion of the study will explore the following dosing concepts:

Administration of significantly higher overall injected radioactivity in comparison to recent Phase 3 clinical trials of other PSMA-targeted radioligand therapies
Front loading of administered radioactivity in early cycles; and
Extending the duration of administration of radioactivity beyond 36 weeks to provide longer time on treatment.
In combination with the promising Phase 1 data for Lutetium (177Lu) rhPSMA-10.1 Injection, these design factors should further support the aim of maximizing treatment response and therefore may enable delivery of better outcomes for patients. The Phase 2 portion of the study is expected to start this quarter.

David Gauden DPhil, CEO of Blue Earth Therapeutics said, "The Phase 1 data provides strong validation of the innovative approach taken on optimizing radioligand therapy by Blue Earth Therapeutics and the inventors of the rhPSMA technology. The relative ratios of tumour to healthy organ absorbed radiation doses are key metrics in establishing a better profile of the risks and potential benefits of radioligand therapies. With radioligand therapies, normal organ toxicity considerations gate the total amount of radioactivity that can be administered, so the more of the radioactivity that accumulates in tumours, the better. Our goal is to substantially increase the potential for prostate cancer patients to benefit compared to available radioligand therapy, and completion of this study moves us closer to making that goal a reality."

About metastatic prostate cancer
In 2025 it is estimated that there will be 50,055 new cases of metastatic prostate cancer in the United States (de novo diagnoses plus recurrence from earlier stage diagnoses).3 Five-year survival for newly diagnosed metastatic prostate cancer is low, 36.6%.4 While death rates from prostate cancer have declined over the past three decades4, there is still considerable room to improve patient outcomes.

About Radiohybrid Prostate–Specific Membrane Antigen (rhPSMA)
rhPSMA compounds are referred to as radiohybrid ("rh"), as each molecule possesses four distinct domains. The first consists of a Prostate–Specific Membrane Antigen–targeted receptor ligand. It is attached to two labelling moieties which may be radiolabeled with diagnostic isotopes such as 18F or 68Ga for PET imaging, or with therapeutic isotopes such as 177Lu or 225Ac for radioligand therapy, all of which are joined together by a modifiable linker which can be used to modulate important pharmacokinetic characteristics. Radiohybrid PSMA offers the potential for targeted treatment for men with prostate cancer and originated at the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive worldwide rights to rhPSMA diagnostic imaging technology from Scintomics GmbH in 2018, and therapeutic rights in 2020, and has sublicensed the therapeutic application to its sister company Blue Earth Therapeutics.