On September 11, 2023 Blue Earth Therapeutics, a Bracco company and emerging leader in the development of innovative next generation therapeutic radiopharmaceuticals, reported results from a series of preclinical analyses designed to evaluate the binding affinity, lipophilicity, cellular internalization and therapeutic efficacy of 225Ac-rhPSMA-10.1 in preclinical models for the treatment of prostate cancer, using 177Lu-rhPSMA-10.1 as a comparator (Press release, Blue Earth Therapeutics, SEP 11, 2023, View Source [SID1234635087]). Results showed that both 225Ac-rhPSMA-10.1 and 177Lu-rhPSMA-10.1 demonstrated excellent PSMA binding affinity, high cellular internalization and similar lipophilicity. Therapeutic response and efficacy were evaluated in a preclinical prostate cancer model which showed that 225Ac-rhPSMA-10.1 significantly suppressed tumor growth relative to control. The data were presented in an oral presentation at the Annual Congress of the European Association of Nuclear Medicine (EANM’23) in Vienna, Austria. 225Ac-rhPSMA-10.1 is an investigational radiohybrid (rh) Prostate-Specific Membrane Antigen-targeted therapeutic radiopharmaceutical, and the lead alpha-emitting candidate in Blue Earth Therapeutics’ oncology development program of next generation therapeutic radiopharmaceuticals.

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"We are pleased that the first presentation of preclinical results from Blue Earth Therapeutics’ prostate cancer program using rhPSMA-10.1 radiolabeled with 225Ac is being made to the nuclear medicine community at the EANM’23 Annual Meeting," said David E. Gauden, D.Phil., Chief Executive Officer of the Company. "Underscoring our commitment to advancing science, we are also honored that the abstract has been recognized as a "Top Rated Oral Presentation" by the Association. 225Ac-rhPSMA-10.1 is our second pipeline compound, and, like our lead Phase 1/2 compound 177Lu-rhPSMA-10.1, it is based on innovative radiohybrid PSMA theranostic technology. The radiohybrid platform enables molecules within the class to be modified and deployed for either diagnostic PET imaging or therapeutic applications, and they can also be developed with both beta- and alpha-emitting therapeutic radioisotopes. The pharmacokinetic profile of rhPSMA-10.1 was carefully optimized during development to deliver high radiation doses to prostate cancer lesions while sparing normal tissues as far as possible, and we are building on that work by radiolabeling it with the powerful alpha-emitting radioisotope, 225Ac.

Dr. Gauden continued, "Results from these preclinical analyses demonstrate a promising therapeutic profile for 225Ac-rhPSMA‑10.1, while using 1,000-fold lower radioactivity than 177Lu-rhPSMA-10.1, with similar in vitro characteristics and in vivo therapeutic efficacy observed for both compounds. 225Ac-rhPSMA-10.1 represents a novel alpha-targeted therapy that we intend to advance into the clinic. IND-enabling studies have been completed and we plan to initiate a Phase 1 clinical study of 225Ac-rhPSMA-10.1 in the first half of 2024."

About the study

The findings presented at EANM’23 evaluated 225Ac-rhPSMA-10.1 and 177Lu-rhPSMA-10.1 in preclinical models for the treatment of prostate cancer. Binding affinity and cellular internalization assays were conducted in LNCaP cells, using 177Lu-PSMA-I&T as a reference compound. The lipophilicity of 225Ac-rhPSMA-10.1 and 177Lu-rhPSMA-10.1 was determined by the shake-flask method, measuring the distribution coefficient in n-octanol and PBS at pH 7.4 (log D7.4). Therapeutic response to single-administration of 225Ac-rhPSMA-10.1 (30 kBq) or 177Lu-rhPSMA-10.1 (30 MBq) was evaluated in the 22Rv1 preclinical model (n=8 per group). Efficacy was assessed based on relative tumour growth (change in tumour volume from treatment administration day/baseline) and survival of treated groups versus untreated controls ≤49 days post-treatment initiation. Body weights were monitored throughout for toxicity assessment.

Results

Both natLa-rhPSMA-10.1 and natLu-rhPSMA-10.1 (natLa and natLu being cold surrogates of 225Ac and 177Lu) showed excellent PSMA binding affinity (IC50 = 3.6±0.6 nM and 1.6±0.1 nM, respectively). High cellular internalization and similar lipophilicity were observed for both 225Ac-rhPSMA‑10.1 and 177Lu-rhPSMA-10.1 (% internalization = 99±14 and 108±5; logD7.4 = -3.4±0.2 and -3.8±0.1; respectively). 225Ac-rhPSMA-10.1 treatment significantly reduced tumour growth in vivo versus controls (from day 14 to 31, p<0.05), and prolonged survival (median survival: 27, 43.5, and 42 days for untreated, 225Ac-rhPSMA-10.1, and 177Lu-rhPSMA-10.1 groups, respectively). There were no significant differences in tumour growth suppression or survival between the 225Ac‑rhPSMA-10.1 and 177Lu-rhPSMA-10.1 groups, and both treatments were well-tolerated.

The results were discussed in an oral presentation, "Preclinical Evaluation of 225Ac-rhPSMA-10.1, a Novel Radiohybrid PSMA Compound for Targeted Alpha Therapy of Prostate Cancer," by Caroline Foxton, Ph.D., Blue Earth Group, Oxford, UK, at the Annual Congress of the European Association of Nuclear Medicine on September 10, 2023. Full session details and the abstract are available in the EANM online program here .

About Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA)

rhPSMA compounds are referred to as radiohybrid ("rh"), as each molecule possesses three distinct domains. The first consists of a Prostate-Specific Membrane Antigen-targeted receptor ligand which attaches to and is internalized by prostate cancer cells. It is attached to two labelling moieties which may be radiolabeled with diagnostic isotopes such as 18F or 68Ga for PET imaging, or with therapeutic isotopes such as 177Lu or 225Ac for radioligand therapy – enabling the potential for a true theranostic technology. They may play an important role in patient management in the future, and offer the potential for precision medicine for men with prostate cancer. Radiohybrid technology and rhPSMA originated from the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive, worldwide rights to rhPSMA diagnostic imaging technology from Scintomics GmbH in 2018, and therapeutic rights in 2020, and has sublicensed the therapeutic application to its sister company Blue Earth Therapeutics. Blue Earth Therapeutics and Blue Earth Diagnostics work closely on the development of 177Lu-rhPSMA-10.1. Currently, Blue Earth Therapeutics’ rhPSMA compounds have not received regulatory approval.

On September 11, 2023 AstraZeneca reported positive results from the FLAURA2 Phase III trial TAGRISSO (osimertinib) in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), compared to TAGRISSO alone for patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, SEP 11, 2023, View Source [SID1234635086]).

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These results were presented today in a Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer (WCLC) (abstract #PL03).

Results showed TAGRISSO plus chemotherapy reduced the risk of disease progression or death by 38% compared to TAGRISSO alone (based on a hazard ratio [HR] of 0.62; 95% confidence interval [CI] 0.49-0.79; p<0.0001). By investigator assessment, the combination extended median PFS by 8.8 months versus TAGRISSO alone. PFS results from blinded independent central review (BICR) were consistent, showing TAGRISSO plus chemotherapy extended median PFS by 9.5 months (based on HR of 0.62; 95% CI 0.48-0.80; p=0.0002). Importantly, a clinically meaningful PFS benefit was observed across all prespecified subgroups, including sex, race, type of EGFR mutation, age at time of diagnosis, smoking history and central nervous system (CNS) metastasis status at baseline.

At the time of this analysis, the overall survival (OS) data were immature however, a favorable trend was observed for TAGRISSO plus chemotherapy.

Pasi A. Jänne, MD, PhD, medical oncologist at Dana-Farber Cancer Institute and principal investigator for the FLAURA2 trial, said: "Patients received nearly nine additional months before their EGFR-mutated non-small cell lung cancer progressed as a result of the addition of chemotherapy to standard-of-care osimertinib, building on the strong efficacy we have already seen with osimertinib monotherapy. With these convincing data, patients may soon have a choice of two highly effective osimertinib-based treatment options in this advanced disease setting."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "The compelling FLAURA2 results add to the extensive evidence supporting TAGRISSO as the backbone therapy in EGFR-mutated non-small cell lung cancer and establish a new benchmark for progression-free survival in this setting. We look forward to bringing this potential treatment regimen to patients with advanced lung cancer to further delay disease progression, especially for patients with the greatest unmet need including those with central nervous system metastasis at diagnosis."

Summary of results: FLAURA2

PFS by INV

PFS by BICR

TAGRISSO plus chemotherapy

(n=279)

TAGRISSO monotherapy

(n=278)

TAGRISSO plus chemotherapy

(n=279)

TAGRISSO monotherapy

(n=278)

Median PFS (in months)i

25.5

(24.7, NCii)

16.7

(14.1, 21.3)

29.4

(25.1, NCii)

19.9

(16.6, 25.3)

Hazard ratio (95% CI)

0.62 (0.49-0.79)

0.62 (0.48-0.80)

p-value

<0.0001

0.0002

Data maturity

51%

43%

i. Data cut-off date was 3 April 2023.

ii. NC: Not calculable

Safety results and discontinuation rates due to adverse events (AEs) were consistent with the established profiles of each medicine and no new safety concerns were reported. Grade 3 or higher AEs from all causes occurred in 64% of patients in the TAGRISSO plus chemotherapy arm versus 27% in the TAGRISSO monotherapy arm.

IMPORTANT SAFETY INFORMATION

There are no contraindications for TAGRISSO
Interstitial lung disease (ILD)/pneumonitis occurred in 3.8% of the 1479 TAGRISSO-treated patients; 0.3% of cases were fatal. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (eg, dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed
Heart rate-corrected QT (QTc) interval prolongation occurs in TAGRISSO-treated patients. Of the 1479 TAGRISSO-treated patients in clinical trials, 0.8% were found to have a QTc >500 msec, and 3.1% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
Cardiomyopathy occurred in 3% of the 1479 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 3.2% of 1233 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. Conduct cardiac monitoring, including assessment of LVEF at baseline and during treatment, in patients with cardiac risk factors. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO
Keratitis was reported in 0.7% of 1479 patients treated with TAGRISSO in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist
Postmarketing cases consistent with erythema multiforme major (EMM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if EMM, SJS, or TEN is suspected and permanently discontinue if confirmed.
Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology can be identified, consider permanent discontinuation of TAGRISSO based on severity
Aplastic anemia has been reported in patients treated with TAGRISSO in clinical trials (0.07% of 1479) and postmarketing. Some cases had a fatal outcome. Inform patients of the signs and symptoms of aplastic anemia including but not limited to, new or persistent fevers, bruising, bleeding, and pallor. If aplastic anemia is suspected, withhold TAGRISSO and obtain a hematology consultation. If aplastic anemia is confirmed, permanently discontinue TAGRISSO. Perform complete blood count with differential before starting TAGRISSO, periodically throughout treatment, and more frequently if indicated
Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose
Most common (≥20%) adverse reactions, including laboratory abnormalities, were leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough
INDICATIONS

TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
TAGRISSO is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
TAGRISSO is indicated for the treatment of adult patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy
Please see complete Prescribing Information, including Patient Information for TAGRISSO.

You may report side effects related to AstraZeneca products by clicking here.

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.2 Each year, there are an estimated 2.2 million people diagnosed with lung cancer globally with 80-85% of patients diagnosed with NSCLC, the most common form of lung cancer.1-3 Approximately 70% of people are diagnosed with advanced NSCLC.4

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.5-7 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.8

FLAURA2

FLAURA2 is a randomized, open-label, multi-center, 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 in combination with 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 centers across more than 20 countries, including in the US, Europe, South America and Asia. This is the analysis of the primary endpoint of 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) metastasis. TAGRISSO (40mg and 80mg once-daily oral tablets) has been used to treat nearly 700,000 patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFRm NSCLC.

TAGRISSO, the only targeted therapy to improve survival in both early- and late-stages of EGFRm NSCLC, is approved as monotherapy in more than 100 countries including in the US, EU, China and Japan. These include for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC (FLAURA), locally advanced or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant treatment of early-stage (IB, II and IIIA) EGFRm NSCLC (ADAURA), where TAGRISSO recently demonstrated a statistically significant and clinically meaningful OS benefit.

AstraZeneca also has several ongoing Phase III trials focused on earlier stages of lung cancer including a trial in the Stage IA2-IA3 adjuvant resectable setting (ADAURA2), and in the Stage III locally advanced unresectable setting (LAURA).

The Company is also researching ways to address tumor 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

On September 11, 2023 Vergent Bioscience, a clinical-stage biotechnology company developing tumor-targeted imaging agents, and its wholly owned subsidiary Vergent Bioscience Australia Pty Ltd, reported that new data presented at the IASLC 2023 World Conference on Lung Cancer (#WCLC23) suggest the company’s tumor-targeted fluorescent imaging agent is active and can safely be used to detect tumor tissue in the lung with high accuracy (Press release, Vergent Bioscience, SEP 11, 2023, View Source [SID1234635085]). Findings from the Phase 2 surgical study evaluating VGT-309 suggest the investigational agent could improve surgeons’ ability to see difficult-to-find and previously undetected tumors in real time to help optimize patient outcomes.

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"The widespread adoption of minimally invasive lung cancer surgery, coupled with increasing numbers of small tumors being detected, have made it much more challenging for surgeons to see all tumor tissue during surgery," said Gavin M. Wright, Ph.D., associate professor and director of Surgical Oncology, St. Vincent’s Hospital, Melbourne, Australia. "The findings from our study confirm that VGT-309 could enhance the success of minimally invasive surgery by improving tumor visualization and reducing the potential for cancer to be left behind."

The Phase 2 study evaluated the safety and efficacy of VGT-309 in 27 individuals with suspected or proven cancer in the lung who were eligible for surgery. Each patient in the study received a VGT-309 infusion on the day prior to or day of surgery. Following an attempt to identify each tumor using standard surgical techniques, researchers used a commercially available near-infrared (NIR) endoscope to assess the lung for the presence of any additional tumor tissue, which was then confirmed by pathology.

The study findings presented today at the WCLC23 provide compelling evidence that VGT-309 has a high affinity for malignant tissue in the lung, increasing the potential that surgeons can identify all tumor tissue during surgery. Of the 27 participants, 23 had confirmed cancer, one had typical carcinoid, and three had non-neoplastic processes. The following tumor types were visualized intraoperatively with VGT-309 and NIR imaging: non-small cell lung cancer (adenocarcinoma and squamous cell carcinoma), metastatic carcinoma with breast origin, and high-grade sarcoma of epithelioid morphology. In two patients, VGT-309 identified tumor tissue in lymph nodes that was pathologically confirmed to be cancer, resulting in upstaging that could potentially impact patient treatment and outcomes.

VGT-309 appeared to be safe and well tolerated across all dose levels studied, with no infusion reactions and only one patient experiencing a serious adverse event – a transient elevated liver-function test that resolved without intervention.

"This study provides encouraging results demonstrating the clinical performance of VGT-309, including the breadth of tumors the agent can help surgeons visualize and its corresponding potential to enhance outcomes from minimally invasive surgery," said John Santini, Ph.D., president and chief executive officer at Vergent Bioscience. "We look forward to expanding on these results in future studies including our upcoming multi-center Phase 2 clinical trial."

About VGT-309

VGT-309 is a tumor-targeted imaging agent designed to enable a complete product solution for optimal tumor visualization during open, MIS, and robotic-assisted surgical procedures. VGT-309 is delivered to patients by a short infusion several hours before surgery. Invented in Professor Matt Bogyo’s Lab at Stanford University School of Medicine, the molecule binds tightly (i.e., covalently) to cathepsins, a family of proteases that are overexpressed across a broad range of solid tumors. This approach provides distinct clinical advantages and positions VGT-309 as an ideal tumor-imaging agent. VGT-309’s imaging component is the near infrared (NIR) dye indocyanine green (ICG), which is compatible with all commercially available NIR intraoperative imaging systems that support MIS technologies and is the preferred dye to minimize confounding background autofluorescence.

On September 11, 2023 Eikon Therapeutics, Inc., which advances breakthrough therapeutics through the purposeful integration of engineering and science, reported that it has completed the previously announced integration of TLR 7 and 8 co-agonists into its clinical development program, and that it expects to discuss the further development of these molecules with the U.S. Food and Drug Administration (FDA) in the fourth quarter (Press release, Eikon Therapeutics, SEP 11, 2023, View Source [SID1234635084]). Separately, the FDA has cleared IMP1734, a highly selective PARP1 inhibitor developed in partnership with Impact Therapeutics, for Phase 1 study initiation, which will also begin in the fourth quarter.

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"Powered by the contributions of our cross-disciplinary organization, Eikon has made important progress in both our early- and clinical-stage pipeline programs," said Roger M. Perlmutter, M.D., Ph.D., CEO and Board Chair of Eikon Therapeutics. "Our advanced analytical tools have enabled Eikon to capitalize on near-term opportunities to bring new medicines to patients. Irrespective of the precise source of chemical leads, Eikon’s projects employ pioneering protein dynamics visualization systems, coupled with advanced, ML-based, data analysis platforms. These systems, together, are fueling our growth."

Eikon’s most advanced candidate, BDB001, a systemically administered TLR 7 and 8 co-agonist, has been studied in nearly 300 patients with treatment-resistant advanced malignancies, and has demonstrated clinical activity both as a single agent and in combination with PD-(L)1 inhibitors. Eikon believes that adverse experiences associated with BDB001 treatment are manageable using Eikon’s proposed clinical dosing regimen.

Separately, in collaboration with Impact Therapeutics, Eikon is advancing IMP1734, a novel, highly potent, PARP1 inhibitor that shows profound biochemical and cellular selectivity versus PARP2, a related enzyme that is thought to contribute disproportionately to the adverse effect profiles of currently marketed PARP1/2 inhibitors. The extraordinary selectivity of IMP1734 for PARP1 supports clinical study of this agent as monotherapy and in combination with other treatment regimens. Eikon anticipates initiating Phase 1 clinical studies of IMP1734 in the United States and other jurisdictions in the fourth quarter. In addition, Eikon and Impact Therapeutics have together planned initiation of IND-enabling studies for a brain-penetrant PARP1 candidate that will enter Phase 1 clinical trials once these IND-enabling studies are successfully completed and reviewed.

"The continued progress of our clinical-stage programs is a testament to our emerging clinical development organization which includes experienced industry professionals who collectively have contributed to more than 100 U.S. regulatory approvals of new medicines over their careers," said Roy Baynes, M.D., Ph.D., Chief Medical Officer of Eikon Therapeutics. "The recent IND clearance for our lead selective PARP1 inhibitor, and the planned initiation of IND-enabling studies of the brain penetrant molecule, further advance the strategic investments we have made in these unique oncology therapeutics and add to our oncology programs exploring the TLR 7 and 8 co-agonist."

Eikon has applied its proprietary technologies to programs spanning oncology, immunology, and neuroscience at various stages of preclinical development. Among these programs are candidates targeting steroid hormone receptors, WRN inhibition, and VCP modulation. Eikon has also begun lead optimization of androgen receptor antagonists that target increasingly common androgen receptor mutants, with the aim of delivering a therapeutic for treatment-refractory, castrate-resistant prostate cancer.

"The growth of our preclinical discovery programs is benefiting significantly from the engineering and automation that powers our pioneering, single molecule tracking-based, discovery platform. With the ability to capture upwards of one hundred thousand protein trajectories in less than a second, we are now analyzing more than one million experimental conditions per month," said Dan Anderson, Ph.D., Chief Scientific Officer of Eikon Therapeutics. "Through AI and machine learning, we are able to rapidly analyze data and inventory molecular interactions with extraordinary scale and precision to support progress across all our drug discovery programs."

Eikon’s CEO will participate in a fireside chat at Morgan Stanley’s 21st Annual Global Healthcare Conference, Monday, September 11 at 10:40 a.m. EDT. A webcast will be available and can be accessed through the conference website or at www.EikonTx.com/news.

On September 11, 2023 OSE Immunotherapeutics SA reported the peer-reviewed publication in Annals of Oncology* of the randomized Phase 3 clinical trial (Atalante-1**) on T-cell epitope cancer vaccine Tedopi in HLA-A2 positive patients with advanced or metastatic NSCLC in monotherapy in third line NSCLC with secondary resistance to immune checkpoint inhibitors (ICI) (Press release, OSE Immunotherapeutics, SEP 11, 2023, View Source [SID1234635083]).

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Tedopi is a novel T-cell epitope-based cancer vaccine targeting five tumor-associated antigens, an activating and differentiated off-the-shelf immunotherapy expanding tumor specific T-lymphocytes in HLA-A2 cancer patients. The article, titled "Randomized Open-Label Controlled Study of Cancer Vaccine OSE2101 Versus Chemotherapy in HLA-A2-positive Patients with Advanced Non-Small Cell Lung Cancer with Resistance to Immunotherapy: ATALANTE-1" features positive data from the randomized international Phase 3 study showing that novel cancer vaccine Tedopi improves overall survival with a better safety and quality of life profile in monotherapy compared to chemotherapy in HLA-A2 positive patients with advanced or metastatic NSCLC who have progressed at least 12 weeks after sequential treatment with chemotherapy and immune checkpoint inhibitors (ICI).

Prof. Benjamin Besse, Director of Clinical Research at Gustave Roussy Institute (IGR, Villejuif, France), and Principal Investigator of the Atalante-1 clinical trial, commented: "Tedopi is the first cancer vaccine to demonstrate positive results on survival in a randomized Phase 3 trial in advanced and metastatic NSCLC cancer patients in 3rd line. A significant reduction of the risk of death by 41% was achieved with a better safety profile and a maintained quality of life. This study, conducted in patients with secondary resistance to immunotherapy, compared Tedopi monotherapy with standard of care docetaxel or pemetrexed chemotherapies. Further evaluation is clearly warranted in a second line of treatment of advanced and metastatic NSCLC, to potentially make this cancer vaccine available to hard-to-treat patients in failure and with high medical needs."

Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics, commented: "Tedopi is the most advanced therapeutic cancer vaccine in clinical development. These Phase 3 data, demonstrating the promising effects, have now been validated in the internationally recognized journal ‘Annals of Oncology’, a major achievement for all involved so, in particular, we’d like to thank warmly the investigators, the patients and their families for their commitment. This Phase 3 positive monotherapy data and moreover the recently announced positive Phase 1 and 2 results using other personalized cancer vaccines in combination to treat resected melanoma or pancreatic cancer patients, highlight the promise of this new therapeutic class of vaccines. The clinical value of our results, re-activating specifically the anti-tumor immune responses, is particularly interesting in patients showing immune escape from checkpoint inhibitors. The confirmatory pivotal Phase 3 trial in preparation (first patient expected early 2024) is planned to support the regulatory registration of Tedopi in secondary resistance to immune checkpoint inhibitors, this time in second line NSCLC treatment."

Main results of the first Phase 3 clinical trial of Tedopi in HLA-A2+ patients with NSCLC

This Phase 3 clinical trial has demonstrated a significant therapeutic benefit in patients with secondary

resistance (1) to immune checkpoint inhibitors (ICI) defined as patients with failure to platinum-based chemotherapy followed by a minimum of 12 weeks ICI treatment (main analysis of the trial). Tedopi demonstrated a favorable benefit/risk ratio versus standard of care (SoC) docetaxel or pemetrexed in advanced HLA-A2+ NSCLC patients with secondary resistance to ICI.

The main results were:

Improved efficacy

1. Overall survival (primary endpoint) was statistically significantly improved for Tedopi:
HR=0.59 (95% CI: 0.38, 0.91) in favor of the Tedopi arm, reduced risk of death by 41%.
44.4% overall survival rate at 1 year with Tedopi versus 27.5% with chemotherapy. A clinically meaningful gain in median overall survival of 3.6 months in favor of the Tedopi arm with Tedopi OS at 11.1 months versus 7.5 months for SoC (p=0.017).

2. Post progression survival was also significantly longer in the Tedopi arm (7.7 months versus 4.6 months; p=0.004, HR=0.46).

Improved safety profile and Quality of Life

The ECOG performance status(2), of maintained general health condition with time to ECOG deterioration was significantly longer in the Tedopi arm (9.0 months versus 3.3 months; p=0.006; HR=0.43).
A better quality of life was observed with Tedopi (p= 0.04). (Global health status: p=0.045; Role Functioning: p=0.025).
A good tolerance profile of Tedopi with fewer Severe Adverse Events grade 3-5 (Tedopi 38% vs SoC 68%, p<0.001). No Treatment Emergent Adverse Effects of concern in the Tedopi arm.
(1) Secondary resistance is defined as failure after a minimum of 12 weeks of Immune checkpoint inhibitor given in sequential chemotherapy – checkpoint inhibitors treatment (Kluger HM et al; Journal for immunoTherapy of Cancer 2020 Defining tumor resistance to PD-1 pathway blockade: recommendations from the first meeting of the SITC (Free SITC Whitepaper) Immunotherapy Resistance Taskforce)
(2) The ECOG score is a performance scale used to quantify the general health condition of a patient. It is subdivided into 5 grades from 0 to 5, ranging from fully active (0) to fully disabled, then to death (5).

ABOUT OSE Immunotherapeutics

OSE Immunotherapeutics is a biotech company dedicated to developing first-in-class assets in immuno-oncology and immuno-inflammation.

The Company’s current well-balanced first-in-class clinical pipeline includes:

Tedopi (immunotherapy activating tumor specific T-cells, off-the-shelf, neoepitope-based): this cancer vaccine is the Company’s most advanced product; positive results from the Phase 3 trial (Atalante 1) in Non-Small Cell Lung Cancer patients in secondary resistance after checkpoint inhibitor failure. Other Phase 2 trials, sponsored by clinical oncology groups, of Tedopi in combination are ongoing in solid tumors.
OSE-279 (anti-PD1): ongoing Phase 1/2 in solid tumors or lymphomas (first patient included). OSE-279 is the backbone therapy of the BiCKI platform.
OSE-127 – lusvertikimab (humanized monoclonal antibody antagonist of IL-7 receptor); ongoing Phase 2 in Ulcerative Colitis (sponsor OSE Immunotherapeutics); ongoing preclinical research in leukemia (OSE Immunotherapeutics).
FR-104/VEL-101 (anti-CD28 monoclonal antibody): developed in partnership with Veloxis Pharmaceuticals, Inc. in transplantation; ongoing Phase 1/2 in renal transplant (sponsor Nantes University Hospital); Phase 1 ongoing in the US (sponsor Veloxis Pharmaceuticals, Inc.).
OSE-172/BI 765063 (anti-SIRPα monoclonal antibody on CD47/SIRPα pathway) developed in partnership with Boehringer Ingelheim in advanced solid tumors; positive Phase 1 dose escalation results in monotherapy and in combination, in particular with anti-PD-1 antibody ezabenlimab; international Phase 1b ongoing clinical trial in combination with ezabenlimab alone or with other drugs in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) and hepatocellular carcinoma (HCC).
OSE Immunotherapeutics expects to generate further significant value from its two proprietary drug discovery platforms, which are central to its ambitious goal to deliver next-generation first-in-class immunotherapies:

BiCKI platform focused on immuno-oncology (IO) is a bispecific fusion protein platform built on the key backbone component of anti-PD1 combined with a new immunotherapy target to increase anti-tumor efficacy. BiCKI-IL-7 is the most advanced BiCKI candidate targeting anti-PD1xIL-7.
Myeloid platform focused on optimizing the therapeutic potential of myeloid cells in IO and immuno-inflammation (I&I). OSE-230 (ChemR23 agonist mAb) is the most advanced candidate generated by the platform, with the potential to resolve chronic inflammation by driving affected tissues to tissue integrity.