On August 18, 2022 Bicara Therapeutics, a clinical-stage biotechnology company developing dual-action biologics designed to elicit a potent and durable immune response in the tumor microenvironment, reported that it will present updated data from the expansion phase of its ongoing Phase 1 trial of BCA101, a bifunctional antibody designed to target the TGFβ trap to EGFR+ tumors, in an oral presentation at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 (Press release, Bicara Therapeutics, AUG 18, 2022, View Source;utm_medium=rss&utm_campaign=bicara-therapeutics-to-present-clinical-data-from-lead-precision-tumor-modulator-program-bca101-at-esmo-congress-2022 [SID1234618479]). The meeting is being held at the Paris Expo Porte de Versailles in Paris, France and virtually from September 9-13, 2022.

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Details of the oral presentation are as follows:

Session Category: Mini Oral session: Investigational immunotherapy
Presentation Title: A phase 1 trial of the bifunctional EGFR/TGFβ fusion protein BCA101 alone and in combination with pembrolizumab in patients with advanced solid tumors
Presenter: Glenn J. Hanna, MD
Date/Time: Saturday, September 10, 2022 at 2:55 p.m. GMT (8:55 a.m. EST)

About BCA101

BCA101 is a first-in-class EGFR / TGF-β-trap bifunctional antibody designed to enhance both innate and adaptive immune responses directly at the site of the tumor by binding to the well-validated EGFR antigen and disabling TGF-β, a signaling molecule that plays a key role in suppressing the immune response in the tumor microenvironment. Promising preclinical data suggest that BCA101 is superior to the anti-EGFR antibody cetuximab in preventing tumor recurrence, as well as in restoring immune activation. An ongoing Phase 1/1b clinical trial of BCA101, initiated in July 2020, has enrolled cohorts of patients in a dose-escalation study with BCA101 as a single agent, as well as in combination with pembrolizumab, a PD-1 inhibitor and a recommended dose for expansion has been declared. For more information, please visit study number NCT04429542 at www.clinicaltrials.gov.

On August 18, 2022 CG Pharmaceuticals, Inc. reported the first patient dosed with the ivaltinostat and capecitabine combination therapy for the Phase 1b/2 pancreatic adenocarcinoma (PDAC) maintenance study (Press release, CG Therapeutics, AUG 18, 2022, View Source [SID1234618496]).

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Commencement of treatment for the first patient began on Aug 15, 2022, and the study will continue to recruit patients in approximately 25 institutions throughout the US.

The Phase 1b study will investigate the safety and tolerability of ivaltinostat in 3 different dose cohorts with locally advanced or metastatic PDAC who have completed at least one prior therapy. In the Phase 2 study, metastatic PDAC patients who show no evidence of disease progression after treatment with FOLFIRINOX will receive either the ivaltinostat/capecitabine combination therapy or capecitabine monotherapy after randomization. The primary endpoint is to evaluate ivaltinostat’s effect on improving progression free survival (PFS), while key secondary endpoints include objective response rate (ORR), disease control rate (DCR), and overall survival (OS).

Dr. Joong Myung Cho, CEO of CG Pharmaceuticals and CrystalGenomics, stated "Dosing of the first patient is a significant milestone for ivaltinostat as there is a great unmet medical need for the PDAC patients. We are very excited about the start of this trial as ivaltinostat has demonstrated promising signs of efficacy from previous preclinical and clinical studies."

About Ivaltinostat

Ivaltinostat is a novel anticancer therapeutic candidate that inhibits enzymatic activity of histone deacetylase (HDAC). Ivaltinostat has been evaluated for anticancer effect for metastatic PDAC and myelodysplastic syndrome (MDS). The results of the Phase 2 study with unresectable or metastatic PDAC patients who have not had prior treatment were 93.8%, 25%, and 10.8 months, respectively for DCR, ORR and median OS. These results were published in the June 2022 publication of "International Journal of Cancer".

On August 18, 2022 Targovax reported its first half and second quarter 2022 results (Presentation, Targovax, AUG 18, 2022, View Source [SID1234618481]).

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On August 18, 2022 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, reported that a case report, titled "Long Term Complete Response of Advanced Hepatocellular Carcinoma to Glypican-3 Specific Chimeric Antigen Receptor T-Cells plus Sorafenib, A case report", has been published in Frontiers in Immunology (https://www.frontiersin.org/articles/10.3389/fimmu.2022.963031/full) (Press release, Carsgen Therapeutics, AUG 18, 2022, View Source [SID1234618497]).

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Hepatocellular carcinoma (HCC) is the most common histologic subtype of primary liver cancer, which is the sixth most common cancer type worldwide. Clinical efficacies of existing therapies for unresectable HCC are still unsatisfactory. CAR T-cell therapy has been approved for a variety of hematological tumors, but there are still great challenges for CAR T-cell therapies to treat solid tumors. We firstly reported GPC3 as a reasonable target for CAR T-cell therapy and thereafter advanced it into clinic.[1,2] In order to further enhance the efficacy of GPC3 CAR T cells, we proposed a new strategy by combining the GPC3 CAR T cells with sorafenib for the treatment of hepatocellular carcinoma[3]. To further validate this strategy in clinical setting, we conducted an investigator-initiated clinical trial at the First Affiliated Hospital of Wenzhou Medical University. The published case reported a patient with advanced HCC who achieved a complete response (CR) and a long survival period after the combination therapy of CAR-GPC3 T-cell plus sorafenib.

The case showed a 60-year-old Asian male patient with hepatitis B virus (HBV)-related HCC who underwent surgery in May 2018. In August 2018, the recurrence of liver cancer and pulmonary metastasis occurred after the operation, and then he received transarterial chemoembolization (TACE) to treat liver lesions and interventional ablation to treat pulmonary metastases. Two months later, he progressed and was enrolled into the clinical trial. After the enrollment, the patient underwent leukapheresis for CAR-GPC3 T-cell manufacturing. Seven days after leukapheresis, the patient started to receive 400 mg of sorafenib twice daily. The patient received 4 cycles of CAR-GPC3 T cells (CT011) treatment and each cycle was divided into two infusions. Prior to each cycle of CT011 treatment, lymphodepletion was performed. A total of 4×109 CAR-GPC3 T cells were infused.

The CT011 plus sorafenib combination therapy was well tolerated. This patient obtained partial responses (PR) from the 3rd month and achieved CR in the 12th month after the first cycle of CT011 infusion. The tumor had no progression for more than 36 months and maintained the CR status for more than 24 months after the first infusion.

To the best of our knowledge, this is the first reported case with a CR after the combination therapy of CAR T cells with tyrosine kinase inhibitors. The clinical outcome demonstrated that the combination therapy of GPC3 CAR T-cell and Sorafenib may be a new promising approach for GPC3+ advanced HCC patients.

Dr. Zonghai Li, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics Holdings Limited, commented that, "There is great expectation for CAR T cells to provide curative potential in treating solid tumors. When enrolled into the clinical trial, the patient in this reported case had undergone local therapies such as TACE and interventional ablation but had not received systemic therapies such as anti-angiogenesis inhibitors. Based on the finding of our earlier preclinical research, we adopted the combination therapy of sorafenib and CT011 as treatment regimens. It was very encouraging to see that the patient achieved a complete response and a long survival period without recurrence for more than two years. While directly indicating that GPC3 CAR T may be used for early-line treatment of HCC, this case report also provides new evidence supporting the adoption of CAR T cells in the early-line treatment of other solid tumors."

About CT011

CT011 is an autologous CAR T-cell product candidate with proof-of-concept clinical data for the treatment of hepatocellular carcinoma (HCC) and has the potential to be the first-in-class globally. Dr. Zonghai Li — Founder, Chairman of the Board, Chief Executive Officer and Chief Scientific Officer of CARsgen Therapeutics — led the world’s first successful effort in identifying, validating, and reporting GPC3 as a tumor-associated target for the development of CAR T-cell therapies to treat HCC. CARsgen has completed enrollment of a Phase I trial in China.

On August 16, 2022 Orna Therapeutics, a biotechnology company pioneering a new class of fully engineered circular RNA therapies (oRNA), reported the initial closing of its $221 million Series B financing (Press release, OrnaTherapeutics, AUG 18, 2022, View Source [SID1234626173]). At signing, the company received approximately $121 million and expects to receive the remaining $100 million subject to customary closing conditions (including regulatory approval under the Hart-Scott-Rodino (HSR) Act). Merck participated as a new investor in the financing alongside commitments from founding investors MPM Capital and BioImpact Capital, an affiliate of MPM, among others. Orna was created in 2019 by MPM Capital and BioImpact Capital, with funding from the UBS Oncology Impact Fund.

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The financing will enable Orna to continue development of its circular RNA + LNP (lipid nanoparticle) delivery platform, as augmented by its joint venture with ReNAgade Therapeutics, an RNA delivery company created by MPM Capital and BioImpact Capital, to advance its lead in situ CAR (isCAR) program toward the clinic and build manufacturing capabilities to support development of an expanding preclinical and clinical pipeline.

"In under three years, Orna has taken proprietary circular RNA from academic literature to the first proof of concept data in preclinical models," said Tom Barnes, Ph.D., Chief Executive Officer of Orna and Entrepreneur at BioImpact Capital. "Investors continue to recognize our premier technology and the hard work of our team, and we are pleased to see such unwavering belief in the potential of circular RNA to revolutionize how we treat disease."

Orna is expanding the reach of current RNA therapeutics with recently presented preclinical data demonstrating the potential of oRNA to treat cancer, genetic disorders, and infectious diseases. Orna’s lead isCAR program demonstrated tumor suppression and eradication in animal models, indicating significant potential that oRNA-based cancer therapies could be superior to traditional cell therapies. With the proceeds of the Series B financing, Orna anticipates advancing this program into clinical trials in 2024.

"In just a few years since we created and built the company, Orna has made remarkable progress in demonstrating the extensive power of its circular RNA + LNP delivery technologies," said Ansbert Gadicke, M.D., Chairman of Orna, Managing Partner of BioImpact Capital and MPM Managing Director. "oRNA, with its numerous advantages over linear mRNA, is the next generation of RNA therapies, and we are excited to see the continued development and applications of this technology."

"It has been validating to see the promise of RNA realized through linear mRNA-based vaccines," said Daniel G. Anderson, Ph.D., Professor of Chemical Engineering and core member of the Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science at MIT, and Co-founder of Orna. "Orna’s next generation of oRNA therapies not only demonstrate promise as vaccines, but also as treatments for a range of diseases where other modalities have fallen short."

SVB Securities acted as financial advisor to Orna on this transaction.