On December 7, 2023 Marengo Therapeutics, Inc., a clinical-stage biotech company pioneering a new way to activate T cells by targeting germline-encoded alleles in the Vβ chain of the T cell receptor (TCR) to selectively activate the right T cell subsets to fight cancer, reported a publication in Science Advances describing the novel immunological effects of its foundational anti-Vβ chain TCR targeting antibodies on human T cells (Press release, Marengo Therapeutics, DEC 7, 2023, View Source [SID1234638269]). This unique approach underpins Marengo’s therapeutic T cell platform, which has broad application across a range of diseases. The publication describes observations and insights gained through a collaboration between Marengo scientists and the Kings College London-based lab of Adrian Hayday, Ph.D. FmedSci, FRS.

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"Professor Hayday and his team are true pioneers in advancing the field of innate TCR biology, particularly in the area of gamma delta T cells," said Andrew Bayliffe, Ph.D., Chief Scientific Officer of Marengo. "Through this collaboration, we have extended the concept of innate TCR engagement to αβ T cells. The resulting learnings will be crucial as we progress our platform and pipeline of broad Vβ T cell therapeutics."

The publication, titled "Innate TCRβ-chain Engagement Drives Human T cells Toward Distinct Memory-like Effector Phenotypes with Immunotherapeutic Potentials," highlights the distinct binding modes of Marengo’s Vβ chain-targeting antibodies and their effects on differentiation states of human T cells. Using a battery of immunophenotyping and molecular approaches, researchers in Professor Hayday’s Immunobiology Lab at King’s College London revealed a unique signature induced in subsets of human T cells treated with Vβ chain-targeting antibodies.

Link to publication: View Source

This population of cells show hallmarks of both proliferative memory T cells, and effector T cells that are highly distinct to states induced by other non-clonal TCR activators such as anti-CD3e antibodies and Vβ chain‑targeting bacterial superantigens. Further mechanistic investigations revealed diverse transcriptional changes associated with the changes in T cell phenotype that suggest a fundamental reprogramming of T cell differentiation by Vβ chain-targeting antibodies.

"We undertook these studies to tackle a previously unanswered question; namely, will TCR∝β respond in a distinct and interesting way to stimulating by an atypical mode, that we term ‘innate’. We have discovered that the answer is clearly yes, and we are understandably delighted for cancer patients that this innate response mode may prove therapeutically beneficial," said Professor Hayday.

This publication follows on the heels of a paper published November 29 in the journal Science Translational Medicine, which further underscores the potential of Marengo’s lead asset STAR0602 and the company’s STAR platform to target and activate subsets of T cells expressing different β chain TCRs.

On December 7, 2023 ARTBIO, Inc. (ARTBIO), a clinical-stage radiopharmaceutical company developing a new class of targeted alpha radioligand therapies (ARTs), reported the closing of an oversubscribed and upsized $90 million Series A financing co-led by Third Rock Ventures and an undisclosed healthcare fund (Press release, ARTBIO, DEC 7, 2023, View Source [SID1234638268]). Additionally, seed lead investors F-Prime Capital and Omega Funds participated substantially. The company’s prior seed investment round of $23 million was announced in June 2023.

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Concurrent with the Series A closing, ARTBIO has appointed industry veterans Philippe Dasse, Pharm.D., as Chief Technical Officer and Daniel Rossetto as Head and Senior Vice President of Supply Chain and External Manufacturing. In these roles, Philippe and Daniel will lead the development and expansion of ARTBIO’s unique distributed manufacturing network in support of the company’s clinical pipeline.

"We are thrilled to have the support of our new and existing investors, including Third Rock Ventures, F-Prime Capital and Omega Funds. These groups bring significant expertise in company scale-up and pipeline development that will be invaluable as we continue to progress our programs and pipeline," said Emanuele Ostuni, Ph.D., CEO of ARTBIO. "Next year will be an important one for the company as we advance our lead program, AB001, and our entire pipeline, while further developing a distributed manufacturing network with our AlphaDirect technology. Bringing Philippe and Daniel to the ARTBIO team also deepens our manufacturing expertise to ensure efficient manufacturing and seamless delivery of our novel Pb212 alpha radioligand therapies to patients."

"The foundational work conducted by the stellar team of experts at ARTBIO has established the potential of alpha radioligand therapies and gives us great confidence that this team can revolutionize today’s cancer treatment paradigm," said Jeff Tong, Partner at Third Rock Ventures. "As ARTBIO is in a rapid scale-up phase, we are looking forward to supporting its growth by leveraging our deep expertise in discovery, development and operations."

The appointments of Philippe and Daniel to the management team strengthen the company’s capabilities during this critical stage. In Philippe’s role as Chief Technical Officer, he will lead the development of ARTBIO’s proprietary AlphaDirect technology and establishment of the company’s distributed manufacturing network. Philippe was most recently Head of Technical Operations for Radioligand Therapies at Novartis Oncology. Philippe was also the first employee of Advanced Accelerator Applications in 2002, a company acquired by Novartis in 2018, and covered increasing responsibilities to lead all technical operations before his departure.

"I am excited to join this talented and passionate team to help build the next wave of innovation in radiopharmaceuticals by pushing the boundaries of the platform and creating a new manufacturing paradigm that leverages my past experiences and adapts to the demands of short-lived alpha emitters," said Dr. Dasse.

In Daniel’s role as Head and Senior Vice President of Supply Chain and External Manufacturing, he will lead efforts to strengthen the company’s supply chain logistics and manufacturing partnerships to ensure the seamless distribution of ARTs. Daniel has a long career in pharmaceutical manufacturing and was most recently the Global Head of Supply Chain at Advanced Accelerator Applications, Novartis. In this role, Daniel managed a diverse team to scale up a high-speed and agile internal and external supply network to deliver the clinical and commercial RLT portfolio which included PLUVICTO to prostate cancer patients.

"The strong Series A funding is a clear sign of the differentiated value proposition and potential of the ARTBIO platform and a recognition of the fast progress that the team has made," said Ted Love, M.D., ARTBIO Board Chairman and Biotechnology Innovation Organization’s (BIO) Board Chairman. "We are grateful to attract such high-quality investors and associated board members whose deep experience in drug discovery and development as well as company building will serve us well as we continue driving our novel pipeline forward."

On December 7, 2023 TransThera Sciences (Nanjing) Inc., a clinical-stage biopharmaceutical company focused on inventing differentiated drugs for global patients, reported that an oral presentation of tinengotinib clinical data in breast cancer was delivered at 2023 San Antonio Breast Cancer Symposium (SABCS) annual meeting (Press release, TransThera Biosciences, DEC 7, 2023, View Source;transthera-announces-an-oral-presentation-of-tinengotinib-clinical-data-in-breast-cancer-302008583.html [SID1234638267]).

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Rapid-Fire Mini-Oral Presentation, Abstract #RF01-07

Title: The efficacy and safety of tinengotinib in patients with advanced or metastatic HR+/HER2- breast cancer or TNBC
Presenter: Sarina A. Piha-Paul, MD
Presentation time: December 6, 2023, 12:15 PM – 1:00 PM (CT)

Results: As of October 1, 2023, 36 patients (pts) with heavily pretreated (median 5 prior lines) metastatic breast cancer (BC) were treated.

Promising clinical benefit:
28 pts receiving tinengotinib monotherapy were efficacy evaluable. 11 pts with HR+/HER2- BC achieved overall response rate (ORR) of 45%, clinical benefit rate (CBR, CR+PR+SD ≥ 24 weeks) of 64%, disease control rate (DCR) of 82% and median progression-free survival (mPFS) of 5.68 months. Partial responses were observed in 3 pts with HER2-zero and 2 pts with HER2 low (1+/2+) pts, respectively. One patient has been on the treatment for over 17 months and is still on-going. 17 pts with TNBC had ORR of 24%, CBR of 29%, DCR of 71% and mPFS of 2.73 months. Notably, 5 TNBC patients who were originally diagnosed as HR+/HER2- breast cancer had achieved 3 partial responses and 2 stable diseases.
Among 6 pts treated with tinengotinib in combination with nab-paclitaxel, 1 TNBC patient achieved PR and the treatment duration lasted for 6.5 months. 3 patients achieved stable diseases.
About tinengotinib

Tinengotinib is an innovative, global phase III stage spectrum-selective kinase inhibitor that exerts antitumor effects by targeting tumor cells and improving the tumor microenvironment. Ongoing clinical trials in the US and China have revealed the potential of tinengotinib to be efficacious in various solid tumors. It was granted the Orphan-Drug Designation and Fast Track Designation by the FDA for the treatment of CCA. In July 2023, tinengotinib was granted the Breakthrough Therapy Designation (BTD) by NMPA in China.

On December 7, 2023 Bio-Thera Solutions, Ltd (688177:SH), a commercial-stage biopharmaceutical company developing a pipeline of biosimilars and innovative assets, reported that the United States Food and Drug Administration (FDA) has approved Avzivi (bevacizumab-tnjn), a biosimilar referencing Avastin (Press release, BioThera Solutions, DEC 7, 2023, View Source [SID1234638265]). Avzivi is Bio-Thera’s second USFDA approved product and is the second biosimilar researched, developed, and manufactured by a Chinese pharmaceutical company to receive FDA approval in the United States.

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The FDA approval of Avzivi was based on a comprehensive analytical, non-clinical and clinical data package submitted by Bio-Thera to the FDA. Extensive analytical characterization between BAT1706 and US and EU Avastin was conducted on structural, physicochemical, and biological properties to support biosimilarity of BAT1706. A randomized double-blind, single-dose, three-arm, parallel phase I study compared the pharmacokinetics, safety, and immunogenicity of BAT1706 with both the US and EU Avastin in healthy volunteers. A randomized, double-blind, three-arm parallel phase III study compared BAT1706 with Avastin for efficacy, safety, and immunogenicity in subjects with advanced non-squamous non-small cell lung cancer. The totality of the evidence demonstrated that BAT1706 has similar efficacy, safety, immunogenicity and quality as the reference product bevacizumab.

"Bevacizumab has been widely used in the treatment for lung and colorectal cancers and many other cancers around the world," commented professor Li Zhang, leading investigator for global phase III study of Avzivi. "The global phase III clinical trial has confirmed that Avzivi is highly similar to Avastin in terms of efficacy, safety and immunogenicity. The approval of Avzivi by the FDA will provide lung and colorectal cancer patients a new cost-effective treatment option. We hope Bio-Thera continues to make more high-quality biosimilars available to patients around the world."

"The approval of Avzivi is another landmark accomplishment for Bio-Thera as it marks Bio-Thera’s second FDA approved product in the United States," said Shengfeng Li, CEO at Bio-Thera. "As our biosimilar pipeline continues to mature, we intend to seek more approvals of biosimilars, expanding patient access to important therapies."

Bio-Thera and Sandoz entered into a license and commercialization agreement for Avzivi (BAT1706) in September 2021. Under the terms of the agreement, Bio-Thera is responsible for the development and manufacturing of the product. Sandoz is responsible for the commercialization of Avzivi in the United States and other countries around the world.

About Avzivi (bevacizumab-tnjn)
Avzivi (bevacizumab-tnjn) is a humanized monoclonal antibody that targets VEGF. It specifically binds to VEGF and blocks the binding of VEGF to its receptor, thereby reducing neovascularization, inducing the degradation of existing blood vessels, and thereby inhibiting tumor growth. The original company name for Avzivi is BAT1706. In the United States, Avzivi is indicated for the treatment of 1) Metastatic colorectal cancer in combination with intravenous fluorouracil-based chemotherapy for first- or second-line treatment, 2) Metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line bevacizumab product-containing regimen. (Limitation of Use: not indicated for adjuvant treatment of colon cancer), 3) Unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer, in combination with carboplatin and paclitaxel for first-line treatment, 4) Recurrent glioblastoma in adults, 5) Metastatic renal cell carcinoma in combination with interferon alfa, 6) Persistent, recurrent, or metastatic cervical cancer, in combination with paclitaxel and cisplatin, or paclitaxel and topotecan, 7) Epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for platinum-resistant recurrent disease who received no more than 2 prior chemotherapy regimens.

ON December 7, 2023 Regor Therapeutics Group ("Regor"), a global innovator powered by cutting-edge drug discovery engine and differentiated clinical development pipeline, reported the results from Phase 1A single agent dose escalation study of RGT-419B, a next generation CDK4 inhibitor, in HR+ HER2- ABC patients who have progressed on prior CDK4/6is and ET (Press release, Regor Therapeutics, DEC 7, 2023, View Source;advanced-breast-cancer-patients-who-have-progressed-on-cdk46-inhibitors-and-endocrine-therapy-302009555.html [SID1234638264]). These results (cutoff date September 26, 2023) were presented today in poster session by Dr. Seth Wander from Massachusetts General Hospital at the San Antonio Breast Cancer Symposium (SABCS) taking place December 5-9, 2023, in San Antonio, Texas. The poster titled "First-in-human Phase 1A study of RGT-419B, a next generation CDK4 inhibitor, in patients with HR+/HER2- ABC who have progressed on prior CDK4/6 inhibitors (PO3-18-06; NCT05304962)", highlighted that:

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Across 12 patients with HR+HER2- ABC who have progressed on CDK4/6is and ET, RGT-419B administered as oral (PO) monotherapy in continuous 28-day cycles was safe and well-tolerated with no dose-limiting toxicities. No patients discontinued treatment with RGT-419B due to an adverse event.
The exposure of RGT-419B was dose proportional with long half-life and small peak to trough ratio at steady state.
RGT-419B demonstrated single agent efficacy in the heavily pretreated HR+/HER2- ABC patients who have progressed on CDK4/6i and ET. Three patients achieved partial responses and are still on treatment. 6 patients received treatment > 24 weeks.
The promising single agent efficacy of RGT-419B is consistent with the preclinical data from CDK4/6i resistant breast cancer models.
"RGT-419B demonstrates its potential to be the best-in-class next generation CDK4 inhibitor for HR+/HER2- breast cancer. The results presented today is encouraging because RGT-419B is not only safe and well tolerated, but also demonstrated single agent efficacy in heavily pre-treated HR+ HER2- ABC patients who progressed on the approved CDK4/6i and ET." said Xiayang Qiu Ph.D., Chief Executive Officer of Regor Therapeutics Group. "These data show that RGT-419B has monotherapy opportunity in HR+ HER2- ABC patients resistant to the approved CDK4/6i and ET. With the favorable safety profile and promising monotherapy efficacy, RGT-419B has best-in-class potential as a single agent or in combination in HR+HER2- BC patients resistant to CDK4/6i, and in earlier lines of treatments. Clinical studies of single agent dose expansion and combination of RGT-419B with ET are underway."

The Phase 1 trial (NCT05304962) is a multicenter, open-label study to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of RGT-419B given as monotherapy or in combination with ET in patients with HR+HER2- ABC who have progressed on CDK4/6i and ET.

Copies of the posters are available on Regor’s website under the Science section.