On May 23, 2024 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported that two clinical abstracts on its lead drug candidate mitazalimab, a best-in-class CD40 agonist, in first line metastatic pancreatic cancer will be presented (abstracts 2569 and 4133) in a poster presentation session at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place in Chicago, IL and online during May 31-June 4 (Press release, Alligator Bioscience, MAY 23, 2024, View Source [SID1234643569]).

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Data presented at ASCO (Free ASCO Whitepaper) from the OPTIMIZE-1 study, of mitazalimab in combination with mFOLFIRINOX chemotherapy, showed that pharmacological analyses identified mitazalimab-induced expansion of CD4 effector T cells one week after first administration as a correlate of treatment outcomes. These data suggest the contribution of mitazalimab to tumor responses, and further supports the unique trial design of OPTIMIZE-1.

OPTIMIZE-1 achieved its primary endpoint, demonstrating a confirmed Objective Response Rate (ORR) of 40.4%, an unconfirmed ORR of 50.9% and a disease control rate (DCR) of 79% in 57 evaluable patients, as per the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). This compares favorably to the ORR of 31.6% reported in a similar patient population treated with FOLFIRINOX alone.[1] Median Duration of Response (DoR) was 12.5 months, remarkably longer than reported so far with any other approved and investigational therapies. Median Overall Survival (OS) was 14.3 months and the survival estimate from the next planned analysis may further improve.

"Most pancreatic cancer patients are diagnosed after the disease has already metastasized. Treatment options at this stage are rather unsatisfactory and there is a major need of novel therapies for these patients. The primary analysis results of OPTIMIZE-1 study suggest that adding mitazalimab to the modified FOLFIRINOX regimen significantly prolongs the durability of response, resulting in a meaningful extension of overall survival in this fatal disease. It is indeed encouraging to see many patients still continuing in the study, and we are very much looking forward to the 18-month survival follow-up from OPTIMIZE-1, which we expect at the end of June 2024," said Dr. Sumeet Ambarkhane, CMO of Alligator Bioscience. "These results support the continued development of mitazalimab in combination with mFOLFIRINOX, in a confirmatory, phase 3, clinical trial in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC). Furthermore, the correlation of mitazalimab-induced immune activation with improved clinical outcomes suggests a potential immunological profile that could be used as a biomarker for this treatment."
The open-label, multi-center OPTIMIZE-1 study assessed the safety and efficacy of mitazalimab (CD40 mAb agonist) in combination with standard of care chemotherapy mFOLFIRINOX, in previously untreated, chemotherapy naïve patients. More details can be found with the clinicaltrials.gov identifier NCT04888312.

Poster Presentations Details
Title: CD4 effector T cell expansion to identify objective responses to the CD40 agonist mitazalimab in combination with modified FOLFIRINOX (mFFX) as first-line therapy for metastatic pancreatic ductal adenocarcinoma (mPDAC) in the OPTIMIZE-1 study
Presenter: Peter Ellmark, PhD
Abstract: 2569
Track: Developmental Therapeutics—Immunotherapy
Location: Hall A | On Demand
Time: 1 June 2024, 09:00 – 12:00 (GMT-5)

Title: OPTIMIZE-1 primary analysis: Safety, efficacy and biomarker results of a phase 1b/2 study combining CD40 agonist mitazalimab with mFOLFIRINOX in previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC)
Presenter: Jean-Luc Van Laethem, MD, PhD
Abstract: 4133
Track: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary
Location: Hall A | On Demand
Time: 1 June 2024, 13:30 – 16:30 (GMT-5)

[1] Conroy et al., N Engl J Med 2011; 364:1817-1825; DOI: 10.1056/NEJMoa1011923

About pancreatic cancer

Pancreatic cancer is the 12th largest cancer by number of patients. It is expected to become the second leading cause of cancer death in the western world by 2030. There are about 200,000 annual cases in the U.S. and the EU, with very poor prognosis: five-year survival is about 10% and median survival about 6 months. For 80% of patients, the only option is chemotherapy that offers only marginal benefit. FOLFIRINOX is expected to be the preferred first line regimen in the U.S. and the EU for patients with good performance status.

On May 23, 2024 2seventy bio, Inc. (Nasdaq: TSVT) reported that members of the management team will present at the following upcoming investor conferences (Press release, 2seventy bio, MAY 23, 2024, View Source [SID1234643567]):

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TD Cowen 5th Annual Oncology Innovation Summit: Insights for ASCO (Free ASCO Whitepaper) & EHA (Free EHA Whitepaper) in a virtual fireside chat on Tuesday, May 28, 2024 at 8:30 a.m. ET
Goldman Sachs 45th Annual Global Healthcare Conference in Miami Beach, FL, on Monday, June 10, 2024 at 8:40 a.m. ET

Live webcasts of the fireside chats will be available via the Investors and Media section of the company’s website at View Source Replays will be archived on the 2seventy bio website for 30 days following the events.

On May 22, 2024 Alphamab Oncology (stock code: 9966.HK) reported that the first patient has been successfully dosed in the phase I clinical study (JSKN016-101) of JSKN016, a novel bispecific antibody-drug conjugate (ADC) targeting HER3 and TROP2, in the treatment of Chinese patients with advanced malignant solid tumors.

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Trophoblast cell surface antigen 2 (TROP2) is widely expressed in solid tumors, and its up-regulation can stimulate tumor growth, proliferation and invasion. Studies have showed that high TROP2 expression was observed in 64% of lung adenocarcinomas, 75% of lung squamous cell carcinoma, and up to 78% of breast cancer. Overexpression of Human epidermal growth factor receptor 3 (HER3) may be associated with poor prognosis of a variety of solid tumors such as lung cancer, breast cancer, gastric cancer, ovarian cancer, and melanoma. Therefore, molecules targeting TROP2 or HER3 may play anti-tumor activity in solid tumors.

JSKN016 is a bispecific antibody-drug conjugate (ADC) simultaneously targeting HER3 and TROP2, which is independently developed by Alphamab. After binding with TROP2 and/or HER3 on the surface of tumor cells, JSKN016 enters the lysosome through target-mediated endocytosis, releasing cytotoxic topoisomerase I inhibitor (TOPIi), and then inducing apoptosis of TROP2 and/or HER3 positive tumor cells. In addition, the inhibitor can penetrate the cell membrane and enter the antigen-negative tumor cells to exert bystander effect. These effects can effectively inhibit the growth of tumor cells.

JSKN016-101 is an open-label, multi-center, first-in-human (FIH) phase I clinical trial of JSKN016, including dose-escalating and dose-expansion phases. The primary endpoint is to evaluate the safety, tolerability, pharmacokinetics (PK)/pharmacodynamics, and antitumor activity of JSKN016 in Chinese patients with advanced malignant solid tumors, as well as to determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D).

About JSKN016

JSKN016 is a bispecific antibody-drug conjugate (ADC) targeting HER3 and TROP2, which is developed inhouse with proprietary Glycan-specific conjugation platform. JSKN016 can induce apoptosis of TROP2 or HER3 positive tumor cells, and penetrate the cell membrane into antigen-negative tumor cells to exert bystander effect, thus effectively inhibiting the growth of tumor cells. The phase I clinical study of JSKN016 for the treatment of advanced malignant solid tumors is currently being conducted in China.

(Press release, Alphamab, MAY 22, 2024, View Source [SID1234657013])

On May 22, 2024 Captain T Cell GmbH, a biotechnology company developing next-generation T cells against solid tumors, reported the successful closing of a seed financing round totaling € 8.5 million (Press release, Captain T Cell, MAY 22, 2024, View Source [SID1234644416]). A syndicate of experienced life science investors including i&i Biotech Fund I SCSp, Brandenburg Kapital GmbH, and HIL-INVENT Ges.m.b.H participated in the round. In addition, the German Federal Ministry of Education and Research (BMBF) is supporting the Company through its prestigious GO-Bio program. The financing also marks the appointment of biotech veteran Jörn Aldag as Chairman of the Board of Directors.

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The funds will be used to further progress Captain T Cell’s first-in-class lead program towards the clinic along with a novel allogeneic platform for off-the-shelf treatments of solid tumors.

Captain T Cell develops first-in-class efficacy-enhanced TCR-T cells for solid tumors that are not addressed by existing therapies. Using a toolbox of next-generation technologies, Captain T Cell generates TCR-T cells with enhanced persistence and the capacity to cope with the hostile tumor microenvironment of difficult-to-treat solid tumors. In preclinical in vivo models, the Company has been able to completely eradicate aggressive tumors using these efficacy-enhanced T cells. A key technology established by the Captain T Cell team is its proprietary TCR-ALLO platform for off-the-shelf treatment of solid tumors. The TCR-ALLO platform is a versatile tool that can be expanded to a variety of cancer indications.

The Company is a spin-off from the renowned Max Delbrück Center, Berlin, Germany, a leading European biomedical research institution. The institute provided valuable financial and infrastructural support throughout the pre-seed phase and together with its technology transfer partner Ascenion remains a close partner for future endeavors.

Dr. Felix Lorenz, CEO of Captain T Cell, said: "This successful financing round allows us to accelerate our high-potential therapies and brings us closer to providing life-saving options for patients underserved by current treatments. We are steadfast in our mission to progress our lead candidate towards the clinic and to establish our TCR-ALLO platform as a leader in off-the-shelf solid tumor therapeutics."

"We have been following the Captain T Cell team for some time and have been impressed by their scientific depth and management capabilities. The team has generated highly convincing preclinical data. Also, we see tremendous potential in their off-the-shelf approach. It holds the promise of bringing life-saving therapies to patients at much lower cost. If successful, it could be applied to any TCR-T cell therapy currently in development, enabling widespread use of these therapies. Captain T Cell has the potential to become a global leader in the development of novel oncology drugs," said Dr. Jaromir Zahrádka, Managing Partner of i&i Bio.

"T cell-based immunotherapies represent a powerful tool in the challenging fight against solid tumors. We believe Captain T Cell is positioned at the forefront of cancer therapy with its unique toolbox technology approach," said Hao Nam Nguyen, Investment Manager at Brandenburg Kapital. "Brandenburg Kapital looks forward to supporting the highly ambitious team at Captain T Cell and to bringing this very promising project to fruition together with our co-investors and the BMBF funding from the GO-Bio program."

"Captain T Cell combines a powerful proprietary drug development platform with an advanced preclinical product pipeline," commented Dr. Friedrich Hillebrand, Managing Director of HIL-INVENT. "The Company’s programs address a high unmet medical need in the treatment of aggressive solid tumors. We are therefore pleased to participate in the Company’s seed financing round and support its future growth."

On May 23, 2024 Orna Therapeutics, a biotechnology company dedicated to designing and delivering a new class of fully engineered circular RNA therapeutics (oRNA), reported its acquisition of ReNAgade Therapeutics, a pioneer in unlocking the potential of RNA therapeutics that demonstrated industry-leading delivery to multiple extra-hepatic cells in non-human primate (NHP) models over the past 18 months (Press release, Orna Therapeutics, MAY 22, 2024, View Source [SID1234643612]).

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Amit D. Munshi, Chief Executive Officer of ReNAgade, will succeed Tom Barnes, Ph.D., to lead Orna as Chief Executive Officer.

"RNA-centric approaches are poised to eclipse traditional cell therapy-based methods and reshape the future of medicine," said Mr. Munshi. "This strategic acquisition unifies Orna’s and ReNAgade’s strengths and capabilities under one roof, expanding technological synergies and multiplying the companies’ depth and breadth of expertise to drive a unique RNA therapeutic-focused R&D engine. Orna will now advance an industry-leading approach combining the Company’s circular RNA expression technology with ReNAgade’s broad portfolio of LNP-based RNA delivery systems and comprehensive editing programs to solve the most pressing challenges in drug development."

An industry veteran of more than 30 years, Mr. Munshi is former President and CEO of Arena Pharmaceuticals Inc., which he built from a $300 million market cap into a late clinical stage company before its acquisition for $6.7 billion by Pfizer. Dr. Barnes will retain his position on Orna’s Board of Directors and serve as chair of its Scientific Advisory Board.

"Orna remains singularly focused on developing the right tools and technologies and building the right company to power an entirely new class of RNA-based medicines," said Dr. Barnes, founding Chief Executive Officer of Orna Therapeutics. "The combination of technologies positions Orna to advance best-in-classpanCAR in vivo CAR RNA therapies and expand existing gene editing delivery solutions with circular RNA to address the massive unmet need in multiple diseases."

"Both Orna and ReNAgade were founded on our bold vision to push the boundaries of RNA medicine," said Ansbert Gadicke, M.D., Managing Partner of MPM BioImpact. "The fusion of these industry leaders in circular RNA and delivery will transform the landscape of RNA therapeutics and accelerate clinical milestones leading to greater impact for patients living with cancer and autoimmune diseases. The combined company is supported by a substantial financial position enabling these milestones."

Built by MPM BioImpact, both Orna and ReNAgade bring significant financing. Orna launched with $100 million in Series A financing in February 2021, subsequently announcing in August 2022 a $221 million Series B in addition to a strategic partnership. ReNAgade launched in May 2023 with $300 million Series A financing. The combined company will have a robust pipeline with panCAR programs in oncology and autoimmune disease, vaccine programs partnered with Merck, and genetic disease programs.