On June 14, 2022 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported a poster presentation on DecisionDx-Melanoma at the recent 2022 Fall Clinical Dermatology Conference for PAs & NPs (Press release, Castle Biosciences, JUN 14, 2022, View Source [SID1234615979]). The poster, titled "Attitudes of Patients with Cutaneous Melanoma Towards Prognostic Testing Using Gene Expression Profiling," shares results from a survey of 120 melanoma patients regarding prognostic testing with DecisionDx-Melanoma. The poster can be viewed here.

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"The number of invasive melanoma diagnoses has risen by 31% over the last decade,1 and in 2022 alone, it is estimated that melanoma will claim over 7,000 lives.2 For this reason, a diagnosis of malignant, invasive melanoma can be terrifying for patients," said Kyleigh LiPira, M.B.A., study author and chief executive officer of the Melanoma Research Foundation (MRF). "In the survey, a significant majority of patients desired testing with DecisionDx-Melanoma after receiving a melanoma diagnosis and appreciated the in-depth information provided by the results, regardless of whether they received low or high-risk scores."

Highlights from survey results:

90% of patients wanted prognostic information about their tumors at diagnosis.
Patients wanted DecisionDx-Melanoma testing to increase their knowledge about their disease (76.9%) and inform treatment decisions (46.2%).
More than 90% of patients felt the testing was useful and that they gained understanding (60.7%) and relief from uncertainty (39.3%).
Patients receiving results from their DecisionDx-Melanoma test did not experience decision regret, even among patients who received a DecisionDx-Melanoma Class 2 (high-risk) test result.
DecisionDx-Melanoma provides personalized information based on a patient’s biological risk of metastasis and recurrence that can aid clinicians and patients in making more informed and risk-aligned decisions about the management of their melanoma.

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma (CM) metastasis or recurrence, as well as the risk of sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 6,300 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. Additionally, Castle has an ongoing collaboration with the National Cancer Institute (NCI) to link DecisionDx-Melanoma testing data with data from the Surveillance, Epidemiology and End Results (SEER) Program’s registries on CM cases. This collaboration has resulted in Castle’s analysis of 5,226 samples (clinically tested through December 31, 2018) in a study to evaluate melanoma-specific survival and overall survival; in this study, patients tested with DecisionDx-Melanoma had better survival rates than untested patients, and the data suggested that DecisionDx-Melanoma can accurately risk-stratify for disease progression to aid in risk-aligned treatment plans for improved patient outcomes and survival. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. Additionally, impact on patient management plans for one of every two patients tested has been shown in five multi-center/single-center studies including more than 800 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. To predict risk of recurrence and likelihood of sentinel lymph node positivity, the Company utilizes its proprietary algorithms, i31-ROR and i31-SLNB, to produce an Integrated Test Result. Through March 31, 2022, DecisionDx-Melanoma has been ordered 97,288 times for patients with cutaneous melanoma.

On June 14, 2022 TILT Biotherapeutics (TILT), a clinical-stage biotechnology company developing cancer immunotherapies, reported it has completed the first close of its financing round raising $10.7 million (€10 million) (Press release, TILT Biotherapeutics, JUN 14, 2022, View Source [SID1234615978]). The round was led by Lifeline Ventures and was joined by Tesi (Finnish Industry Investment Ltd). The funding will be used to advance Phase I/II programs in Europe and the US, using TILT-123 plus immune checkpoint inhibitors against a range of cancers including ovarian, head & neck, and lung.

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The company also announces the appointment of Dr. Tuija Keinonen, PhD (Pharm), as Chair of the Board. Tuija brings specialist industry experience in life sciences business development and clinical trial operations across Europe and Asia.

TILT Biotherapeutics’ founder and CEO, Akseli Hemminki, a cancer clinician who has personally treated hundreds of cancer patients, said, "I’m delighted to announce a solid financing for the company, and to warmly welcome Tuija Keinonen as Chair of the Board. Tuija brings a wealth of experience which will be a great asset as we progress our pipeline of armed oncolytic viruses. These are showing excellent potential in the clinic to increase the anti-tumor benefits of checkpoint inhibitors for a range of cancers where there’s a pressing need for better therapies.

TILT Biotherapeutics’ Chair, Tuija Keinonen, said, "I’m able to use my international business and clinical operations expertise to support TILT’s growing clinical footprint. We now have several clinical trials running in Europe and the US and are planning more."

Lifeline Ventures’ Founding Partner, Timo Ahopelto, said, "We support resilient founders. We saw early on the enormous potential in TILT’s innovative approach to boost the patient’s T cell immune response to better enable it to find and destroy cancer cells."

"TILT is one of the most promising biotech companies in Finland. We are excited to back the development of the company’s innovative treatments for cancer types with currently limited treatment options. Despite the enormous developments in cancer treatments over the past decade, there is still a significant need for new therapies," said Miia Kaye, Investment Manager at Tesi.

On June 14, 2022 MAIA Biotechnology, Inc., a targeted therapy, immuno-oncology company focused on developing potential first-in-class oncology drugs ("MAIA"), reported that MAIA has entered into a research and collaboration agreement with the Nationwide Children’s Hospital to evaluate the potential of THIO in combination with current standard-of-care therapies for cancer (Press release, MAIA Biotechnology, JUN 14, 2022, View Source [SID1234615977]). THIO is MAIA’s proprietary, first-in-class, telomere-targeting small molecule currently in clinical development to evaluate its activity in non-small cell lung cancer (NSCLC).

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Through this research collaboration, the organizations will conduct preclinical studies to assess the efficacy and safety of THIO in combination with radiotherapy and immune checkpoint inhibitors in vitro and in vivo.

"We are thrilled to partner with Nationwide Children’s Hospital, a leading pediatric teaching hospital focused on advancing the health and well-being of all children, and in particular, those suffering with cancer," said Vlad Vitoc, M.D., MAIA’s Chairman and Chief Executive Officer. "We believe that THIO has the potential to be used as a broad anticancer agent and we are excited to evaluate its activity in preclinical models with checkpoint inhibitors and radiation therapies. We are proud to align with Nationwide to advance this potentially ground-breaking scientific work."

"Cancer is one of the leading causes of death in children beyond infancy in the United States, and while important strides have been made in identifying and developing treatments, more research is needed to advance further," said Rachid Drissi, Ph.D., principal investigator in the Center for Childhood Cancer and Blood Diseases at the Abigail Wexner Research Institute at Nationwide Children’s Hospital. "We’re excited to continue that advancement here, so families can focus on their children’s future, and not their disease."

Sergei Gryaznov, Ph.D., Chief Scientific Officer of MAIA, added, "Childhood cancer rates have been steadily rising in the past few decades, and more than 10,000 children in the US under the age of 15 will be diagnosed with cancer just this year alone. The combination studies under the Nationwide collaboration will grow the body of growing evidence we have with THIO and will advance research in the field of pediatric cancer."

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a telomere-targeting agent currently in clinical development to evaluate its activity in NSCLC. Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. THIO is being developed for patients with NSCLC that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.

On June 14, 2022 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 biodistribution and potential therapeutic efficacy of 177Lu-rhPSMA-10.1 and 177Lu-PSMA-I&T in the treatment of prostate cancer preclinical models (Press release, Blue Earth Therapeutics, JUN 14, 2022, View Source [SID1234615976]). Results from preclinical biodistribution studies demonstrated that 177Lu‑rhPSMA-10.1 performed favorably when compared with 177Lu-PSMA-I&T, with an improved tumor:kidney uptake ratio. Therapeutic efficacy was evaluated in a preclinical prostate cancer xenograft model which showed that 177Lu‑rhPSMA‑10.1 significantly suppressed tumor growth relative to control, and to a greater extent than 177Lu-PSMA-I&T. The data were presented in an oral presentation at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting. 177Lu-rhPSMA-10.1 is an investigational radiohybrid (rh) Prostate-Specific Membrane Antigen-targeted therapeutic radiopharmaceutical, and the lead candidate in Blue Earth Therapeutics’ oncology development program of next generation therapeutic radiopharmaceuticals.

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"Radioligand therapy targeting prostate-specific membrane antigen (PSMA) has been shown to be an effective therapy in men with metastatic castration-resistant prostate cancer," said Caroline Foxton, Ph.D., Vice President R&D Strategy and Collaboration at the Blue Earth Group. "However, optimizing tumor uptake and accelerating renal clearance for this class of compounds could improve the therapeutic index, achieve better clinical outcomes and effectively manage radiation exposure to patients. Blue Earth Therapeutics’ next generation therapeutic rhPSMA compound has been optimized for favorable biodistribution properties to enhance delivery of therapeutic radiation to tumors while minimizing kidney uptake and retention. Supported by these preclinical data, 177Lu‑rhPSMA-10.1 was selected as our lead therapeutic candidate for progression to the clinic."

"We are pleased that the first presentation of preclinical results from Blue Earth Therapeutics’ rhPSMA-10.1 program in prostate cancer is being made to the nuclear medicine community at the SNMMI 2022 Annual Meeting," said David E. Gauden, D.Phil., Chief Executive Officer of the Company. "Radiohybrid PSMA technology enables utility as a theranostic because the molecule may be modified and deployed for either diagnostic PET imaging or therapeutic applications. This optimized rhPSMA technology can also be developed with both beta- and alpha-emitting therapeutic radioisotopes, with the potential to deliver personalized, targeted therapy specific to each patient’s condition. We are closely collaborating in the development of 177Lu-rhPSMA-10.1 with our sister company, Blue Earth Diagnostics, by incorporating its investigational 18F-rhPSMA-7.3 PET agent into our clinical development program."

Dr. Gauden continued, "Results from these analyses demonstrate the attractive preclinical biodistribution and potential therapeutic efficacy profile of 177Lu-rhPSMA-10.1, and were included in our Investigational New Drug application to the U.S. Food and Drug Administration. Blue Earth Therapeutics’ Phase 1/2 clinical trial for 177Lu-rhPSMA-10.1 in treating men with metastatic castrate‑resistant prostate cancer was recently cleared to proceed, and we expect patient enrollment to commence shortly."

Results
The findings presented at SNMMI included biodistribution data from preclinical models which evaluated 177Lu-rhPSMA-10.1 and 177Lu-PSMA-I&T uptake and tumor:kidney ratio, and therapeutic efficacy analysis in preclinical prostate cancer xenograft models.

Biodistribution
Data from longitudinal biodistribution analyses in preclinical models showed that the most significant organ uptake for both 177Lu-rhPSMA-10.1 and 177Lu-PSMA-I&T was observed in the kidney; however, kidney retention was lower for 177Lu-rhPSMA-10.1 than 177Lu-PSMA-I&T at all timepoints, and 6.5-fold lower than that for 177Lu-PSMA-I&T at 12 hours. No other organ (including the brain) showed any significant uptake of 177Lu-rhPSMA-10.1. A single-timepoint biodistribution study using a PSMA-expressing prostate cancer xenograft model examined the tumor:kidney uptake ratio for both compounds. It also showed lower kidney uptake of 177Lu‑rhPSMA‑10.1, with kidney uptake being 6.4‑fold lower for 177Lu-rhPSMA-10.1 than for 177Lu‑PSMA-I&T at 15 hours post-injection. Higher tumor uptake was seen with 177Lu‑rhPSMA‑10.1 than 177Lu-PSMA-I&T at this timepoint (2.3-fold), resulting in an improved tumor:kidney ratio for 177Lu-rhPSMA-10.1 (2.3±1.14) compared to 177Lu-PSMA-I&T (0.1±0.03).

Efficacy
The potential therapeutic efficacy of 177Lu-rhPSMA-10.1 and 177Lu-PSMA-I&T was compared in a PSMA-expressing prostate cancer xenograft model. Tumor volume was significantly reduced by 177Lu-rhPSMA-10.1 compared with the vehicle control (p=0.045 at 35 days after treatment). When measuring fold-change in tumor volume relative to volume at inclusion, 177Lu-rhPSMA-10.1 showed a statistically significant suppression of tumor growth compared to both non-radiolabeled rhPSMA-10.1 and vehicle control at both 14 days after treatment (p<0.01 both comparisons) and 35 days after treatment (p<0.01 vs non-radiolabeled rhPSMA-10.1 and p<0.001 vs vehicle). 177Lu-PSMA-I&T also reduced tumor growth compared with vehicle control (p<0.05), but to a lesser extent than 177Lu‑rhPSMA‑10.1. No significant effects were noted on any hematological parameters or body weight.

The results were discussed in an oral presentation, "Preclinical evaluation of a novel radioligand therapy for patients with prostate cancer: biodistribution and efficacy of 177Lu-rhPSMA-10.1 in comparison with 177Lu-PSMA-I&T," by Caroline Foxton, Ph.D., Blue Earth Group, Oxford, UK, at the SNMMI 2022 Annual Meeting on June 13, 2022. Full session details and the abstract are available in the SNMMI 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 either 18F for PET imaging, or with isotopes such as 177Lu or 225Ac for therapeutic use – creating 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, rhPSMA compounds have not received regulatory approval.

On June 14, 2022 AVM Biotechnology, a clinical stage company advancing AVM0703 in the treatment of Non-Hodgkin’s Lymphoma (NHL)/Leukemia, reported that it has been awarded a Phase II Small Business Innovative Research (SBIR) grant (Press release, AVM Biotechnology, JUN 14, 2022, View Source [SID1234615975]). This $2 million National Cancer Institute (NCI) grant will assist in the continuation of the company’s existing clinical trial (AVM0703 for Treatment of Leukemia or Lymphoma, NCT04329728).

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This Phase II grant has been awarded for continued support of the adaptive-design, expansion cohort clinical trial of AVM0703 for "no-option," Relapsed/Refractory (R/R) NHL/Leukemia patients. The study is currently enrolling at City of Hope, UCLA, Norton Cancer Institute, and the University of Texas Southwestern. Additional sites are being brought on-line.

AVM0703:

is a small molecule which triggers the production and release of endogenous bispecific gamma delta TCR+ invariant TCR+ Natural Killer T-like cells (AVM-NKT).
induces AVM-NKT cells rapidly in the blood following a single dose.
is currently the subject of an adaptive design expansion cohort clinical trial with the dose escalation phase nearing completion and the efficacy phase projected to commence soon.
In the ongoing dose escalation phase, which included 11 highly refractory patients who had been heavily pretreated averaging 5.3 prior lines of therapy with 6 of 11 having failed hematopoietic stem cell transplantation (HSCT) or CAR-T, results included:

100% clinical response at 18 mg/kg target Ph II dose, with durable partial response/stable disease ongoing out to greater than 9 months in 1 patient.
Of 10 evaluable patients from the dose-escalation; 4 experienced partial response and 2 other patients subsequently reached complete remission.
An additional 20% achieved stable disease or significant clinical response including durable vision restoration in 1 patient.
One heavily pretreated patient with T-cell lymphoma who did not meet inclusion/exclusion criteria received AVM0703 under an FDA-approved Compassionate Use Program. That patient has experienced a very good partial response.

The drug has been well-tolerated with no reported Dose Limiting Toxicities (DLTs) or grades 4 or 5 adverse events. AVM0703 also potentiates chemotherapy and CAR-T response in pre-clinical models.

NHL is the 7th most common cancer in the US with over half of the 77,240 diagnosed annually over the age of 65. Even with treatment, disease recurs or relapses in approximately 50% of these patients and many become refractory to additional treatment. Patients can undergo many lines of various therapies including chemotherapy, radiation, CAR-T and HSCT which can be associated with significant toxicities and poor outcomes with many relapsing and requiring additional treatment. Based on its strong safety profile and clinical response, AVM0703 presents an appealing alternative to these therapies.

"AVM0703 represents an exciting new treatment option for NHL patients who have failed other therapies or who do not qualify for further chemotherapy, radiation, or cell therapies, including CAR-T. In addition to improvement in disease status, several patients treated with AVM0703 in the dose-escalation phase of the study have qualified for other treatments they had formerly been excluded from accessing," said Joe Luminiello, CEO.

AVM Biotechnology previously received a Phase I NCI grant from the National Institutes of Health (NIH) to study the use of AVM0703 as a preconditioning agent to allow safe and efficient delivery of therapeutic immune cells for cancer treatment. The company has requested breakthrough therapy designation and plans for accelerated approval for commercial launch in mid 2024.