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 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 Alpha Tau Medical Ltd. ("Alpha Tau", or the "Company") (NASDAQ: DRTS, DRTSW), the developer of the innovative alpha-radiation cancer therapy Alpha DaRT, reported the publication of an article entitled "Extended Follow-Up Outcomes from Pooled Prospective Studies Evaluating Efficacy of Interstitial Alpha Radionuclide Treatment for Skin and Head and Neck Cancers" in the journal Cancers, with further detail on data previously announced by the Company in August 2023. The publication was authored by clinical investigators from Israel, Italy and the United States and can be accessed through the following link: View Source

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The aim of the analysis was to evaluate the long-term toxicity outcomes and disease control rates for patients treated with Alpha DaRT and followed for up to four years. In this pooled analysis of 81 treated head and neck, oral cavity and skin tumors from four clinical trials with a median follow-up of 14 months (range of 2—51 months), the overall response rate was 99%, with a complete response observed in 89% of treated lesions, a 10% partial response rate, and one patient non-evaluable. Two-year local recurrence-free survival was 77%, and there were no grade 2 or higher late toxicities observed. Clinical variables, including recurrent versus non-recurrent lesions, baseline tumor size, or histology, did not impact long-term outcomes.

The published results indicate that the Alpha DaRT treatment may provide tumor control even beyond the acute treatment period of short-term local responses, potentially leading to longer-term disease control. The lack of moderate or severe toxicities observed in this analysis is promising and suggests that Alpha DaRT may potentially offer an appropriate long-term treatment for these very difficult-to-treat cancers. Further follow-up and additional clinical studies are ongoing and will provide additional characterization of the safety and efficacy profile of Alpha DaRT.

Alpha Tau CEO Uzi Sofer stated, "We are encouraged by the perspective offered by this long-term data and its publication in a renowned journal such as Cancers. The publication of this comprehensive pooled analysis reinforces our belief in the sustained benefit of Alpha DaRT for patients with hard-to-treat cancers who have limited treatment options. We have additional ongoing studies in multiple tumor types and this long-term safety and efficacy snapshot shows great promise for the future when fighting the most difficult cancers. We are now poised for our next breakthrough and will continue working hard making excellent progress in our exciting clinical pipeline."

Dr. Robert Den, M.D., Alpha Tau CMO, commented, "The publication of this long-term analysis is extremely gratifying. After years of research, the combined picture shows great clinical promise with no moderate or severe long-term toxicity. Now that we have a published study with a range of up to 51 months with strong durability and a favorable safety profile, we are hopeful this will provide a new therapeutic pathway for patients who have few options. In addition, we are looking forward to results from several ongoing and planned clinical trials in pancreas, brain, vulva, lung and liver metastases."

Prof. Aron Popovtzer M.D., Head of the Sharett Institute of Oncology at Hadassah Medical Center in Jerusalem, and lead author of the publication, commented, "This analysis presents in fully published form, for the first time, an enhanced clinical picture of the potential benefit that Alpha DaRT may provide to patients with these hard-to-treat skin, head and neck cancers. The long-term analysis of safety and efficacy compares very favorably to other radiotherapeutic studies using external beam radiation, but with a much lower incidence of complications. We are excited and hopeful about the future potential of Alpha DaRT in the treatment of various solid tumors and in combination with systemic therapies such as immunotherapy and chemotherapy."

About Alpha DaRT

Alpha DaRT (Diffusing Alpha-emitters Radiation Therapy) is designed to enable highly potent and conformal alpha-irradiation of solid tumors by intertumoral delivery of radium-224 impregnated sources. When the radium decays, its short-lived daughters are released from the sources and disperse while emitting high-energy alpha particles with the goal of destroying the tumor. Since the alpha-emitting atoms diffuse only a short distance, Alpha DaRT aims to mainly affect the tumor, and to spare the healthy tissue around it.

On June 25, 2024 Charles River Laboratories International, Inc. (NYSE: CRL) and the Gates Institute at the University of Colorado Anschutz Medical Campus reported a lentiviral vector contract development and manufacturing organization (CDMO) agreement (Press release, Charles River Laboratories, JUN 25, 2024, View Source [SID1234644543]). Gates Institute will leverage Charles River’s premier cell and gene therapy CDMO expertise to develop Good Manufacturing Practice (GMP)-grade lentiviral vectors (LVVs) for use in novel chimeric antigen receptor (CAR) T-cell therapies for hematological cancers.

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The Gates Institute mission at the University of Colorado Anschutz Medical Campus is to develop and deliver advanced therapies in cell and gene therapy. The Institute brings together researchers, clinicians, and a GMP biomanufacturing facility for first-in-human clinical trials. Through this strategic collaboration, Gates Institute will have access to Charles River’s established manufacturing platforms and dedicated viral vector CDMO center of excellence, utilizing a range of services including process development evaluation of Gates Institute’s LVV backbone, phase-appropriate research grade and High –Quality (HQ) plasmid DNA production, and GMP LVV manufacturing. Materials produced within the collaboration will support an upcoming Investigational New Drug (IND) application for Phase I clinical trials.

Plasmid DNA and Viral Vector Manufacturing Services

With over 20 years of plasmid DNA and viral vector CDMO expertise and validated platform processes including eXpDNA and Lentivation with a proven track record, Charles River has standardized protocols and high-yield, optimized methods to accelerate speed to clinical and commercial manufacturing by reducing process development time and costs while ensuring premium quality production.

In recent years, Charles River has significantly broadened its cell and gene therapy portfolio with several acquisition integrations and expansions to simplify complex supply chains and meet the growing demand for plasmid DNA, viral vector, and cell therapy services. Combined with the company’s legacy testing capabilities, Charles River offers a premier "concept to cure" advanced therapies solution.

To learn more about LVV design, manufacturing, and regulation, join Charles River for a roundtable webinar to examine key trends, address manufacturing challenges, and overcome quality control and regulatory hurdles: https://bit.ly/3Ttijzz

Approved Quotes

"The cell therapy ecosystem that Gates Institute has created is exciting and we look forward to helping them advance the development of CAR-T therapies for hematological cancers. Our complementary strengths and concept to cure capabilities are well positioned to help move the science forward into the clinic and beyond for oncology patients." – Kerstin Dolph, Corporate Senior Vice President, Biologics Solutions, Charles River
"We value this new partnership with Charles River, an industry leader in biopharmaceutical services. In the near term, this collaboration will accelerate the Gates Institute CAR-T programs with their plasmid and lentiviral vector production. Looking ahead to our long-term collaboration, we remain committed to advancing patient impact more broadly." – Terry Fry, MD, Executive Director, Gates Institute

On June 25, 2024 AstraZeneca reported that Tagrisso (osimertinib) with the addition of pemetrexed and platinum-based chemotherapy has been approved in Japan for the 1st-line treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) whose tumours have exon 19 deletions or exon 21 (L858R) mutations (Press release, AstraZeneca, JUN 25, 2024, View Source [SID1234644510]).

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The approval by the Japanese Pharmaceuticals and Medical Device Agency (PMDA) was based on the results from the FLAURA2 Phase III trial, which were also published in The New England Journal of Medicine.

Results showed Tagrisso with the addition of chemotherapy reduced the risk of disease progression or death by 38% by investigator assessment compared to Tagrisso monotherapy, which is the 1st-line global standard of care (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.49-0.79; p<0.0001). Median progression-free survival (PFS) was 25.5 months for patients treated with Tagrisso plus chemotherapy, an 8.8-month improvement versus Tagrisso monotherapy (16.7 months).

PFS results by blinded independent central review were consistent with results by investigator assessment, showing 29.4 months median PFS with Tagrisso plus chemotherapy, a 9.5-month improvement over Tagrisso monotherapy (19.9 months) (HR 0.62; 95% CI 0.48-0.80; p=0.0002).

While the overall survival (OS) remained immature at the second interim analysis (41% maturity), an encouraging trend towards an OS benefit was observed with Tagrisso plus chemotherapy versus Tagrisso alone (HR 0.75; 95% CI 0.57-0.97), presented at the 2024 European Lung Cancer Congress (ELCC) in Prague, Czech Republic (abstract #4O). The trial continues to assess OS as a key secondary endpoint.

Lung cancer is the most common cause of cancer-related deaths both globally and in Japan.1-2 Lung cancer is the second most prevalent cancer type in Japan with more than 135,000 patients diagnosed each year.2 Among those with NSCLC, the most common form of lung cancer, approximately 36% of patients in Japan have tumours with an EGFR mutation.3 Additionally, the majority of patients with NSCLC are diagnosed with advanced disease.4

Kunihiko Kobayashi, MD, PhD, Professor at Saitama Medical University International Medical Center and a principal investigator in the trial, said: "The FLAURA2 results showed osimertinib with the addition of chemotherapy provided a nearly nine-month improvement in progression-free survival versus osimertinib monotherapy. This approval brings an important new treatment option for this aggressive form of lung cancer, the leading cause of cancer death in Japan."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "Today’s approval in Japan solidifies Tagrisso as the backbone therapy for patients with EGFR-mutated lung cancer either in combination with chemotherapy or as monotherapy, now providing two effective first-line treatment options. The opportunity to combine Tagrisso with chemotherapy is especially important for those patients with a poorer prognosis, such as those whose disease has spread to the brain or those with L858R mutations."

The safety profile of Tagrisso plus chemotherapy was consistent with the established profiles of the individual medicines. Adverse event (AE) rates were higher in the Tagrisso plus chemotherapy arm, driven by well-characterised chemotherapy-related AEs. Discontinuation rates of Tagrisso due to AEs were 11% for Tagrisso plus chemotherapy and 6% for monotherapy.

Tagrisso is approved as monotherapy in more than 100 countries including in the US, EU, China and Japan. Approved indications include for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant treatment of early-stage EGFRm NSCLC. Tagrisso with the addition of chemotherapy is also approved in the US and several other countries for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC.

Notes

Lung cancer
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into NSCLC and small cell lung cancer.1 Each year there are an estimated 2.4 million people diagnosed with lung cancer globally, with 80-85% of patients diagnosed with NSCLC, the most common form of lung cancer.4-6

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.7-9 Patients with EGFRm NSCLC are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which blocks the cell-signalling pathways that drive the growth of tumour cells.10

FLAURA2
FLAURA2 is a randomised, open-label, multi-centre, global Phase III trial in the 1st-line treatment of patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients were treated with Tagrisso 80mg once-daily oral tablets with the addition of chemotherapy (pemetrexed (500mg/m2) plus cisplatin (75mg/m2) or carboplatin (AUC5) every three weeks for four cycles, followed by Tagrisso with pemetrexed maintenance every three weeks.

The trial enrolled 557 patients in more than 150 centres across more than 20 countries, including in the US, Europe, South America and Asia. The primary endpoint is PFS. The trial is ongoing and will continue to assess the secondary endpoint of OS.

Tagrisso
Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. Tagrisso (40mg and 80mg once-daily oral tablets) has been used to treat nearly 800,000 patients across its indications worldwide and AstraZeneca continues to explore Tagrisso as a treatment for patients across multiple stages of EGFRm NSCLC.

There is an extensive body of evidence supporting the use of Tagrisso in EGFRm NSCLC. Tagrisso is the only targeted therapy to improve patient outcomes in early-stage disease in the ADAURA Phase III trial, locally advanced stages in the LAURA Phase III trial and late-stage disease in the FLAURA Phase III trial and FLAURA2 Phase III trial.

As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, Tagrisso is also being investigated in the neoadjuvant setting in the NeoADAURA Phase III trial with results expected later this year and in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial.

The Company is also researching ways to address tumour mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III trial, which test Tagrisso plus savolitinib, an oral, potent and highly selective MET TKI, as well as other potential new medicines.