On December 22, 2023 Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") reported that it has completed the acquisition of Propella Therapeutics, Inc. (President and CEO: William Moore, "Propella"), and has become a wholly owned subsidiary of Astellas as of U.S. Eastern Time December 21, 2023 (Press release, Astellas, DEC 22, 2023, View Source [SID1234638743]).

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Through the acquisition of Propella, Astellas has acquired PRL-02 (abiraterone decanoate), a next-generation androgen biosynthesis inhibitor being developed by Propella to treat prostate cancer. PRL-02 is a novel, long-acting prodrug* of abiraterone that, following intramuscular injection, is expected to achieve high concentrations in target tissues where the active moiety, abiraterone, is continuously released. PRL-02 may provide improved efficacy and safety compared to existing treatment options by high CYP17 lyase inhibition selectivity. PRL-02 is currently in a Phase 1 clinical trial and is expected to enter Phase 2a clinical trials in 2024.

Under the agreement, Astellas paid approximately US $175 million to acquire all of the outstanding common stock and equity interests in Propella.

The impact of this transaction on Astellas’ financial results in the fiscal year ending March 31, 2024, will be limited.

On December 21, 2023 Exscientia plc (Nasdaq: EXAI) reported that Sanofi is adding a new discovery stage programme identified and initially advanced by Exscientia into the current collaboration (Press release, Exscientia, DEC 21, 2023, View Source [SID1234638770]). In this programme, Exscientia has designed a novel lead series with a potential best in class profile, with preliminary data showing good potency and selectivity towards the target and differentiated molecular properties.

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"Sanofi adding an Exscientia discovery stage programme into the collaboration speaks to the strengths of our AI-driven platform to solve complex drug discovery problems," said Professor Andrew Hopkins FRS FMedSci, founder and Chief Executive Officer of Exscientia. "The growth of our collaboration is a testament to our strong relationship with Sanofi and our shared vision for AI-enabled drug discovery. As we enter 2024, we expect to continue working with partners to apply our platform capabilities across therapeutic areas while maintaining our internal pipeline focus on high value oncology targets."

Under the terms of the amended agreement, Exscientia is eligible for up to $45 million in upfront and preclinical milestone payments. Exscientia will also be eligible for additional development, regulatory and sales-based milestone payments of over $300 million and tiered royalties on product sales ranging from high-single-digits to mid-teens, as described in the original collaboration agreement. The upfront payment is expected to be reflected in the first quarter 2024 results for Exscientia as cash inflows from collaborations and recognised as revenue over the duration of the agreement.

On December 21, 2023 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, reported a new study published in Molecular Oncology comparing the performance of mean tumor molecules per milliliter (MTM/mL) against mean variant allele frequency (mVAF) for measuring circulating tumor DNA (ctDNA), using Signatera, Natera’s personalized and tumor-informed molecular residual disease (MRD) test (Press release, Natera, DEC 21, 2023, View Source [SID1234638769]). The full study can be found here.

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To date, mVAF and MTM/mL are the two main metrics that have been used to quantify ctDNA levels in the blood. Unlike mVAF, which is a fraction that can be confounded by changes in total background cfDNA, MTM/mL takes into account total cfDNA as well as plasma volume. The premise is that MTM/mL is therefore more representative of a patient’s true disease burden, a hypothesis that was validated in this study.

The study analyzed ctDNA data generated in 55,183 ctDNA-positive samples from 23,543 patients who underwent testing with Signatera for various cancer diagnoses, and it reported the correlation between MTM/mL and mVAF, as well as the correlations of each with patient outcomes.

Key findings include:

Among the 18,426 patients with longitudinal ctDNA measurements, 13.3% had discordant ctDNA trajectories (increase/decrease) when calculated using MTM/mL versus mVAF.
In patients with stage IV disease receiving immunotherapy (N=51), ctDNA dynamics measured in MTM/mL were more predictive of therapy response than those measured in mVAF, with a hazard ratio (HR) nearly 2x higher (MTM/mL HR 16, p<0.0001; mVAF HR 8.8, p<0.0001).
In a case study of a patient with metastatic triple-negative breast cancer, disease progression during systemic therapy was reflected in increasing MTM/mL values, while mVAF levels remained stable.
"We are pleased to see the publication of these important findings, in which MTM/mL provided a more accurate measure of ctDNA than mVAF, particularly for patients undergoing active therapy which can impact the levels of background cfDNA," said Minetta Liu, M.D., chief medical officer of oncology at Natera. "Clinicians need tools to enable reliable predictions of therapy response and clinical outcomes. As the only MRD test that uses MTM/mL, this study supports the utility of Signatera for ctDNA quantification, to measure treatment response at critical time points and inform decisions on how patients are managed."

About Signatera

Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard of care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer (stage IIb and higher) and muscle invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 50 peer-reviewed papers.

On December 21, 2023 ImmunoScape, a biotechnology company focused on next-generation T Cell receptor (TCR)-based immunotherapies, reported a partnership with the Experimental Drug Development Centre (EDDC), Singapore’s national platform for drug discovery and development hosted by the Agency for Science, Technology and Research (A*STAR) (Press release, immunoSCAPE, DEC 21, 2023, View Source [SID1234638768]).

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ImmunoScape’s core antigen-specific T cell immune profiling technology was developed at A*STAR’s Singapore Immunology Network and is exclusively licensed from A*STAR. Since its spinout from A*STAR in 2016, ImmunoScape has developed a cutting-edge, high-throughput, TCR discovery platform that produces a broad and emerging portfolio of novel, safe, and efficacious TCRs against solid tumors.

In this new partnership, ImmunoScape will leverage its catalog of highly potent tumor-specific TCR candidates for the joint development of innovative off-the-shelf TCR-based bispecific molecules with EDDC. These molecules contain two distinct binding sites and are engineered to bind and activate T cells, redirecting them towards tumor sites for interaction with cells expressing the unique tumor-specific antigen through the TCR. This approach enables the patient’s own T cell repertoire to selectively eliminate cancer cells. EDDC will apply its expertise in therapeutic protein design and antibody engineering to develop these novel TCR-based bispecific molecules.

"The benefit of off-the-shelf TCR molecules is that they do not require engineering and manufacturing of the patients’ own T cells, which can make them accessible to a much broader patient population and further results in much lower production costs and shorter timelines for the patients to receive the drug," said Choon-Peng Ng, CEO of ImmunoScape. "By combining the power of our machine learning-augmented TCR discovery platform with EDDC’s broad expertise in the design of multifunctional constructs, we will aim to rapidly develop novel off-the-shelf TCR-based bispecific molecules that could overcome widespread challenges in cell therapy approaches against solid tumors."

"We are thrilled to join forces with ImmunoScape to design and produce TCR-based bispecific constructs that could lead to more effective treatments for solid tumors," said Damian O’Connell, CEO of EDDC. "Our deep expertise in progressing projects from discovery and production of antibodies to the design of multifunctional constructs, paired with ImmunoScape’s TCR discovery platform and library of tumor-specific TCRs, will allow us to jointly develop molecules for sensitive and effective tumor targeting in a T cell-independent manner."

The collaboration is set to commence in early 2024.

On December 21, 2023 RenovoRx, Inc. ("RenovoRx" or the "Company") (Nasdaq: RNXT), a clinical-stage biopharmaceutical company developing novel precision oncology therapies based on a local drug-delivery platform, reported the expansion of their clinical development pipeline in preparation for the commencement of a second Phase III trial (Press release, Renovorx, DEC 21, 2023, View Source [SID1234638767]). The CouGar Trial will evaluate RenovoGem in bile duct cancer, specifically unresectable locally advanced extrahepatic cholangiocarcinoma (eCCA).

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"We are pleased to engage our first clinical site for our second pivotal clinical trial. The CouGar Trial marks an important milestone for RenovoRx as we expand our clinical pipeline for RenovoGem into bile duct cancer, a difficult-to-treat solid tumor cancer," said Leesa Gentry, Senior Vice President of Clinical Operations at RenovoRx. "I’m extremely proud of our team and our collaborators for their tremendous work reinforcing our mission to improve patient lives by delivering innovative therapies that can potentially change the current paradigm of cancer care."

The pivotal Phase III CouGar study is a randomized study designed to evaluate the safety and efficacy of unresectable, locally advanced eCCA using intravenous cisplatin, gemcitabine, and durvalumab (all forms of chemotherapy) versus Trans-Arterial Micro-Perfusion via RenovoGem (delivery system and gemcitabine) with intravenous durvalumab. Oklahoma University (OU) Health is the first clinical site for the CouGar study.

"Unfortunately, bile duct cancer today has a poor prognosis for patients. Despite early diagnosis, the five-year survival rate is approximately 24%," said Paula Novelli, MD FSIR, CouGar National Principal Investigator, and Associate Professor of Radiology and Director of Interventional Radiology Research at the University of Pittsburgh Medical Center. "There are currently limited treatment options for patients diagnosed with this aggressive cancer, which only prolongs life by a few months. The CouGar study brings hope for a new treatment option. RenovoGem has the potential to meet the urgent clinical need for a safe and effective therapy in this important patient population."

Dr. David Geller, Director, UPMC Liver Cancer Center, Richard L. Simmons Professor of Surgery, University of Pittsburgh School of Medicine is the CouGar study’s Co-Investigator.

"The current standard of care for bile duct cancer is systemic (intravenous) chemotherapy, which has poor uptake and delivery since there are few blood vessels feeding this type of tumor," said Dr. Hassan Hatoum, Principal Investigator, Associate Professor and Hematologist and Oncologist at Oklahoma University Health Stephenson Cancer Center – Gastrointestinal Cancer Clinic. "RenovoRx’s clinical trial is evaluating targeted, trans-arterial delivery of chemotherapy that is locally directed to the tumor site. Our team looks forward to participating in the CouGar study to bring this novel therapy to patients."

RenovoGem received FDA Orphan Drug Designation for pancreatic cancer and bile duct cancer which provides 7 years of market exclusivity upon NDA approval.