On June 25, 2024 CDR-Life Inc. reported an expansion of its pipeline of novel T cell engagers (TCE) with the addition of CDR813 and CDR505 (Press release, CDR-Life, JUN 25, 2024, View Source [SID1234644542]).

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CDR813 is a highly potent and selective TCE candidate targeting tumors expressing PRAME (preferentially expressed antigen in melanoma) in HLA-A*02:01 patients. PRAME is a clinically validated pan-cancer target expressed in a broad set of tumors including non-small cell lung cancer (NSCLC), endometrial cancer, melanoma and ovarian cancer, but not in normal tissue. A bi-valent and bi-specific antibody-based TCE, CDR813 targets a PRAME peptide presented on tumor cells by the HLA-A*02 complex and the CD3 receptor on T-cells with unparalleled potency and specificity.

CDR505 is a TCE targeting KK-LC-1, a novel HLA-A*01 target relevant in common cancer populations not yet addressed by other T cell receptor (TCR) therapeutics. While most TCE programs target the HLA-A02 haplotype, CDR505 targets KK-LC-1/HLA-A*01, expanding the potential of TCEs to benefit a large patient population with high unmet need. Preclinical data on CDR505 was presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2024.

"With our continued investment in building a broad pipeline of unique, potent and highly cancer-targeted therapies, we are expanding the promise of our differentiated T cell engager platform to treat a range of solid tumors," said Christian Leisner, Ph.D., Chief Executive Officer at CDR-Life. "Importantly, the CDR813 and CDR505 programs are geared toward populations with significant unmet medical need, increasing our reach to benefit more patients."

On June 25, 2024 Exsilio Therapeutics ("Exsilio"), a biotechnology company developing genomic medicines for a broad range of diseases, reported its emergence from stealth with $82 million in Series A financing (Press release, Exsilio Therapeutics, JUN 25, 2024, View Source [SID1234644541]). The funding was co-led by Novartis Venture Fund and Delos Capital, with participation from OrbiMed, Insight Partners, J.P. Morgan Life Sciences Private Capital, CRISPR Therapeutics, Innovation Endeavors, Invus, Arc Ventures, and Deep Insight. Exsilio was seed-funded by OrbiMed.

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Exsilio will use proceeds from the financing to advance its genomic medicines based on naturally occurring, programmable genetic elements that can precisely insert new genes into a cell through mRNA intermediates. Exsilio’s interdisciplinary team has built a platform that combines predictive in silico modeling and wet lab-based experimentation to discover and engineer such elements for integration of therapeutic genes into safe harbor sites. Because Exsilio’s medicines are encoded in mRNA, they can be delivered using existing lipid nanoparticle (LNP) platforms that are safe, efficient, scalable, and cost-effective, and can be redosed and titrated with curative intent.

"mRNA-based medicines allow for a software-like approach to creating new medicines," said Tal Zaks, M.D., Ph.D., who serves as Exsilio’s Chairman and Interim Chief Executive Officer. "Exsilio’s approach leverages the advantages of mRNA and goes a step further by encoding genes that integrate permanently, offering the possibility of curative rather than transient effects. The ability to insert whole genes with a repeatable and titratable approach should allow us to treat genetic diseases irrespective of the patient’s individual mutation. This financing will help us advance our genomic medicines and select promising lead candidates so that we can bring much-needed new options to patients."

"We were captivated by Exsilio’s genomic medicines approach that stands to enable large-gene integration in a safe and redosable manner," said Aaron Nelson, Managing Director at Novartis Venture Fund and Exsilio Board Member. "Through this significant investment, Exsilio will be able to select and advance promising candidates for difficult-to-treat diseases."

"We believe that the vision of safely and durably integrating therapeutic genes into a patient’s genome requires using RNA-based payloads that can leverage clinically validated non-viral gene delivery technologies," said Henry Chen, Managing Partner of Delos Capital and Exsilio Board Member. "Exsilio is bringing together a singular group of people to help establish this new pillar of genomic medicine."

On June 25, 2024 Carisma Therapeutics Inc. (Nasdaq: CARM) ("Carisma" or the "Company"), a clinical-stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported that Steven Kelly, President and Chief Executive Officer, will participate in a fireside chat at the Stifel 2024 Cell Therapy Forum on Tuesday, July 9th at 9:10 am ET (Press release, Carisma Therapeutics, JUN 25, 2024, View Source [SID1234644540]).

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An audio webcast of the event will be available on the Company’s Investor Events section of the Investor Relations webpage and will be archived for a limited time following the event.

On June 25, 2024 Carisma Therapeutics Inc. (Nasdaq: CARM) ("Carisma" or the "Company"), a clinical stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for CT-0525, an ex vivo gene-modified autologous chimeric antigen receptor-monocyte (CAR-Monocyte) cellular therapy intended to treat solid tumors that overexpress human epidermal growth factor receptor 2 (HER2) (Press release, Carisma Therapeutics, JUN 25, 2024, View Source [SID1234644539]).

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The FDA’s Fast Track program is aimed to facilitate the development, and expedite the review, of novel potential therapies that are designed to treat serious conditions and have the potential to address significant unmet medical need.

"Receiving Fast Track designation for CT-0525 from the FDA marks a significant milestone for Carisma, highlighting the FDA’s recognition of the serious and life-threatening nature of these malignancies and the potential of CT-0525 to meet this critical medical need," said Eugene P. Kennedy, M.D., Chief Medical Officer of Carisma. "We are committed to working closely with the FDA to accelerate the development of CT-0525. Currently, we are enrolling patients in the Phase 1 clinical trial and remain on track to report initial clinical data by the end of 2024."

The Phase 1 clinical trial for CT-0525 is an open-label study designed to assess the safety, tolerability, and manufacturing feasibility of CT-0525. This trial will enroll participants with locally advanced (unresectable) or metastatic solid tumors overexpressing HER2 whose disease has progressed on standard approved therapies. The initial study design will consist of two dose escalation cohorts. Further details of the trial can be found at www.clinicaltrials.gov under NCT identifier: NCT06254807.

About CT-0525

CT-0525 is a first-in-class, ex vivo gene-modified autologous chimeric antigen receptor-monocyte (CAR-Monocyte) cellular therapy intended to treat solid tumors that overexpress human epidermal growth factor receptor 2 (HER2). It is being studied in a multi-center, open label, Phase 1 clinical trial for patients with advanced/metastatic HER2-overexpressing solid tumors that have progressed on available therapies. The CAR-Monocyte approach has the potential to address some of the challenges of treating solid tumors with cell therapies, including tumor infiltration, immunosuppression within the tumor microenvironment, and antigen heterogeneity. CT-0525 has the potential to enable significant dose escalation, enhance tumor infiltration, increase persistence, and reduce manufacturing time compared to macrophage therapy.

On June 25, 2024 IDEAYA Biosciences, Inc. (Nasdaq:IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported that it has dosed its first patient in the IDEAYA-sponsored Phase 1 trial evaluating the combination of IDE397, IDEAYA’s investigational MAT2A inhibitor, and Trodelvy (sacituzumab govitecan-hziy), Gilead’s Trop-2 directed ADC, in patients with MTAP-deletion bladder cancer (Press release, Ideaya Biosciences, JUN 25, 2024, View Source [SID1234644538]).

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"We are pleased to have dosed our first patient with MTAP-deletion bladder cancer in this Phase 1 trial evaluating combination treatment with IDE397 and Trodelvy. The MAT2A-Trop2 ADC combination targets two distinct, yet complementary nodes in patients with MTAP-deleted urothelial cancer and has first-in-class potential to improve clinical outcomes for bladder cancer patients with poor prognosis associated with MTAP-deletion," commented Dr. Darrin M. Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

The IDE397 and Trodelvy combination Phase 1 trial is included as an arm of an ongoing IDEAYA-sponsored clinical trial (NCT04794699), which includes a Phase 2 expansion arm of IDE397 monotherapy in MTAP-deletion solid tumors. The global Phase 1 clinical trial will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of IDE397 in combination with Trodelvy. IDE397 is a potent and selective small molecule inhibitor targeting methionine adenosyltransferase 2 alpha (MAT2A) in patients having solid tumors with methylthioadenosine phosphorylase (MTAP) deletion.

Gilead’s Trodelvy is currently approved in nearly 50 countries for 2L metastatic triple-negative breast cancer and in more than 30 countries for pre-treated HR+/HER2- metastatic breast cancer (mBC). In the U.S., Trodelvy has an accelerated approval for the treatment of patients with locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and anti-PD-(L)1 therapy.

Pursuant to the clinical study collaboration and supply agreement, IDEAYA and Gilead retain the commercial rights to its respective compounds, including with respect to use as a monotherapy or combination agent. IDEAYA is the study sponsor and Gilead will provide the supply of Trodelvy to IDEAYA.

There is separately an Amgen-sponsored Phase 1/2 trial of IDE397 and AMG 193 combination in MTAP-Deletion NSCLC (NCT05975073) for which the companies intend to develop a joint publication strategy in 2024. The Company is targeting a clinical data update for the IDE397 Phase 2 monotherapy expansion dose in MTAP-deletion bladder and lung cancer in over ~15 evaluable patients in the second half of 2024. The Company is also advancing multiple preclinical stage MTAP-deletion programs to enable wholly-owned combinations with IDE397, including a program targeting a Development Candidate nomination in the second half of 2024.

IDE397 monotherapy or in combination with Trodelvy has not been approved by any regulatory agency and the efficacy and safety of this combination has not been established.