On February 3, 2022 Synthekine Inc., an engineered cytokine therapeutics company, reported the dosing of the first patient in a Phase 1a/1b clinical trial of its IL-2 partial agonist, STK-012, for the treatment of solid tumors. STK-012 is designed as an alpha/beta-biased IL-2 partial agonist to selectively stimulate antigen-activated T cells, which are associated with potent anti-tumor activity, and avoid stimulation of toxicity causing immune cells, such as natural killer cells (Press release, Synthekine, FEB 3, 2022, View Source [SID1234607716]).

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"We are proud to begin this year with the important milestone of dosing the first patient in our Phase 1 trial of STK-012," said Debanjan Ray, chief executive officer of Synthekine. "STK-012 is a highly differentiated IL-2 partial agonist tuned to expand the therapeutic index of IL-2 by biasing towards efficacy driving antigen-activated T cells and away from toxicity causing lymphocytes, such as natural killer (NK) cells. STK-012 is the first program from our broad portfolio of biased cytokines to enter the clinic, and its rapid progress into clinical investigation further highlights our team’s tremendous ability to execute efficiently and move our pipeline forward."

Aldesleukin (recombinant IL-2) has shown to be active in certain cancers, but its use is limited due to life threatening toxicities such as capillary leak syndrome (CLS). Synthekine presented preclinical data at AACR (Free AACR Whitepaper) 2021 demonstrating a mouse surrogate of STK-012 achieved superior tumor regression compared to both wild-type mouse IL-2 and a non-alpha-IL-2 agent, representing a different approach to biasing IL-2. In toxicity models, the mouse surrogate of STK-012, unlike these same comparators, was well tolerated and did not induce CLS. In non-human primate studies, STK-012 avoided lymphopenia, NK cell activation and CLS induction, which was observed with both aldesleukin and a non-alpha-IL-2 agent.

The Phase 1a/1b clinical trial is an open-label, multi-center study enrolling patients with advanced solid tumors. The dose escalation portion of the study will evaluate STK-012 both as a monotherapy and in combination with pembrolizumab. Following completion of the dose escalation, Synthekine will initiate expansion cohorts with STK-012. For additional information about the trial, please visit www.clinicaltrials.gov using the identifier NCT05098132.

On February 3, 2022 Sprinter Health, an on-demand mobile health service bringing personalized and affordable healthcare services to the home, reported a collaboration with Naveris, a molecular diagnostics company dedicated to improving patient care through early detection of virus-related cancers (Press release, Naveris, FEB 3, 2022, View Source [SID1234607715]).

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The partnership will improve the detection, treatment, and clinical management of HPV-driven cancers, such as head and neck cancers, by augmenting the convenience of Naveris’ lead product, NavDx, which requires regular blood draws. Patients living in Sprinter Health service areas will be able to easily schedule a visit from a Sprinter Health nurse or phlebotomist (also known as "Sprinters") to collect blood specimens for the test in the comfort of their homes.

The NavDx blood test uses proprietary technology to detect circulating tumor tissue modified HPV (TTMV) DNA. NavDx helps healthcare providers optimize the clinical management of HPV-driven cancer by accurately assessing treatment response, identifying the presence of post-treatment molecular residual disease, and conveniently monitoring for recurrence. The test has been shown to accurately detect cancer recurrence a median of four months earlier than it would present clinically via PET or CT scan, which can facilitate earlier intervention of salvage therapy.1

"Patients being monitored with NavDx need regular blood draws, so we want to make sure they have a consistent, positive experience and don’t have to navigate a complex system just to get their blood specimens collected," said Piyush Gupta, CEO of Naveris. "Sprinter Health’s tech platform makes booking appointments easy for our patients and customer support reps, and they have become a partner we can count on to deliver high quality, reliable care that our patients love."

"Barriers to access can hold back progress toward better care. Lowering these barriers starts with using technology to improve the patient experience," said Max Cohen, CEO of Sprinter Health. "My father is an oncologist, and I’ve seen firsthand the difficult journeys of patients and families experiencing cancer. We’re proud to play a small part in helping patients access Naveris’ innovative test, and look forward to expanding our partnership throughout 2022."

Both companies have been working together in California for several months and plan to expand the partnership to new states in the first half of 2022.

On February 3, 2022 Castle Biosciences, Inc. (Nasdaq: CSTL), a leader in transforming disease management and improving patient outcomes through innovative diagnostics, reported a 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 cutaneous melanoma (CM) cases (Press release, Castle Biosciences, FEB 3, 2022, View Source [SID1234607713]).

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CM cases in the SEER registries that were diagnosed between 2013-2018 were linked with DecisionDx-Melanoma results and additional clinicopathologic information from patients tested between 2013-2018. The Company expects to continue collaborating with the NCI to link the SEER registries’ CM cases diagnosed post-2018 with DecisionDx-Melanoma test results. The initial linked dataset is expected to be broadly available to interested researchers through the standard data request process for SEER Specialized Datasets in 2022.

Data analysis from the first subset of patients was shared in a poster presentation at the 2022 Winter Clinical Dermatology Conference, held Jan. 14-19 in Koloa, Hawaii.

"We are excited to collaborate with the NCI to link DecisionDx-Melanoma test results with the SEER registries’ data," said Derek Maetzold, president and chief executive officer of Castle Biosciences. "Castle is committed to providing clinically actionable tests to improve patient outcomes. Analysis from the first subset of patients (65 years or older at time of diagnosis and diagnosed in 2016 or later) provides real-world evidence of the capability of our test to do just that. Specifically, when controlling for demographic and clinicopathological variables, patients tested with DecisionDx-Melanoma had better overall survival rates over 2.5 years than patients not tested."

The poster, titled "31-gene expression profile testing survival benefit in a population-based analysis of cutaneous melanoma patients ≥65 years of age," highlighted the first analysis of Castle’s DecisionDx-Melanoma testing data in the NCI’s SEER Program registry. The poster can be viewed here.

Study methods and findings:

DecisionDx-Melanoma is Castle’s gene expression profile test that uses an individual patient’s tumor biology to predict the risk of cutaneous melanoma metastasis or recurrence, as well as the risk of sentinel lymph node (SLN) positivity, independent of traditional staging factors. Among other outputs of the test, DecisionDx-Melanoma classifies a patient’s tumor as lowest risk of recurrence/metastasis (Class 1A), increased risk of recurrence/metastasis (Class 1B/2A) or highest risk of recurrence/metastasis (Class 2B).
All incident CM cases diagnosed between 2013-2018 in the NCI’s SEER Program registry were included in the study. The SEER registries linked CM cases in the registry to DecisionDx-Melanoma testing data provided by Castle Biosciences.
While all CM diagnoses between 2013-2018 were included in the linkage, this analysis was limited to a subset of 2,048 patients with Stage I-III melanoma who were ≥65 years or older at the time of diagnosis and were diagnosed between 2016-2018 to account for access to adjuvant therapy.
Patients tested with DecisionDx-Melanoma were successfully matched to those not tested with DecisionDx-Melanoma based on clinical, pathological and demographic data.
After matching, patients tested with DecisionDx-Melanoma had better overall survival rates than patients who had not been tested, demonstrating a direct effect of DecisionDx-Melanoma testing on patient survival (hazard ratio=0.66 compared to untested patients, p=0.002).
The results also confirmed DecisionDx-Melanoma’s ability to stratify patient risk in an unselected, prospectively tested population of CM patients into low (Class 1A) and high-risk (Class 2B) mortality groups.
Patients who received a DecisionDx-Melanoma high-risk result had a ten-fold increase in death rate compared to patients who received a low-risk result (12.3% death rate for a Class 2B result compared to 1.5% for a Class 1A result), demonstrating the independent prognostic value of the test.
In sum, the study data provide direct evidence that CM patients tested with DecisionDx-Melanoma have better survival rates than untested patients, suggesting that the test can aid in risk-aligned treatment plans for improved patient outcomes and survival rates.
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 metastasis or recurrence, as well as risk of sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 6,000 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. 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. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 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 Sept. 30, 2021, DecisionDx-Melanoma has been ordered 84,195 times for use in patients with cutaneous melanoma.

More information about the test and disease can be found at www.CastleTestInfo.com.

About the SEER Program

The Surveillance, Epidemiology and End Results (SEER) Program (View Source) is an authoritative source for cancer statistics in the United States. The SEER Program provides information on cancer statistics in an effort to reduce the cancer burden among the U.S. population and is supported by the Surveillance Research Program (SRP) in the NCI’s Division of Cancer Control and Population Sciences (DCCPS). The SEER Program registries collect data on cancer cases diagnosed in their catchment area from various locations and sources throughout the United States. Data collection began in 1973 with a limited number of registries and continues to expand to include even more areas and demographics today covering 48% of US population. The SEER Program registries link to data provided by a variety of federal and commercial partners to support the research community in conducting cancer surveillance and epidemiological research. The data are available to qualified researchers.

On February 3, 2022 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company enabled by its proprietary synthetic lethality approach to the discovery and development of novel therapeutics, reported that members of its senior management team will participate in two virtual investor conferences in February (Press release, Repare Therapeutics, FEB 3, 2022, View Source [SID1234607712]). Details are as follows:

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Guggenheim Oncology Conference
Date: Thursday, February 10, 2022
Time: 2:00 p.m. Eastern Time

11th Annual SVB Leerink Global Healthcare Conference
Date: Friday, February 18, 2022
Time: 3:00 p.m. Eastern Time

A live webcast of the Guggenheim Oncology Conference fireside chat will be available starting Thursday, February 10, 2022 at 2:00 p.m. Eastern Time in the Investor section of the Company’s website at View Source A replay of the webcast will be archived on the Company’s website for 90 days.

A live webcast of the 11th Annual SVB Leerink Global Healthcare Conference presentation will be available on Friday, February 18, 2022 at 3:00 p.m. Eastern Time in the Investor section of the Company’s website at View Source A replay of the webcast will be archived on the Company’s website for 90 days.

On February 3, 2022 Promega reported that Researchers from Johns Hopkins University have shown that a new panel of long mononucleotide repeats (LMR) might offer advantages over traditional microsatellite instability (MSI) detection methods in certain types of solid tumors (Press release, Promega, FEB 3, 2022, View Source [SID1234607711]). The study, published in the February issue of Journal of Molecular Diagnostics, is the first to use the PCR-based Promega LMR MSI Analysis System to detect MSI in endometrial, prostate and other cancers.

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Detecting Microsatellite Instability

MSI analysis measures changes in the length of specific DNA sequences that occur because of a deficiency in a cell’s DNA mismatch repair system. MSI status is a valuable indicator for predicting whether an individual might respond to immune checkpoint inhibitor therapy. The Promega MSI Analysis System, Version 1.2 is the current gold standard for PCR-based MSI testing and has been relied upon by global clinical researchers for nearly two decades. The assay amplifies a panel of five mononucleotide repeat markers, each composed of 21-27 repeated adenine bases. This technology is used in the OncoMate MSI Dx Analysis System, which is available as a CE-IVD in Europe and an FDA-cleared IVD medical device in the United States.

The LMR MSI Analysis System, launched in February 2021, consists of eight markers – four of the gold standard markers, plus four novel LMR markers that have 52-60 repeated adenine bases each. Longer markers are typically more "unstable," or prone to replication errors, so it has been hypothesized that this new panel of markers might offer greater sensitivity for MSI detection in cancers where the results are otherwise inconclusive or ambiguous.

LMR Analysis Research

The research group led by Dr. James Eshleman, M.D., Ph.D. validated the LMR MSI panel using colorectal, endometrial, and prostate tumor samples, as well as a variety of other tumor samples with inconclusive results in previous MSI testing.

Statistics for the LMR MSI panel include:

Colorectal cancer: 100% accuracy, 100% clinical sensitivity, 100% clinical specificity
Endometrial cancer: 98% accuracy, 98% clinical sensitivity, 100% clinical specificity
Prostate cancer: 75% clinical sensitivity
Other cancers: 100% concordance between LMR MSI and MSI V1.2 in 22 samples previously designated MSI-High
"The new LMR panel clearly offers unique benefits in certain cancer types," says Jeff Bacher, Senior Research Scientist at Promega and co-author on the study. "These results are encouraging for the detection of microsatellite instability in samples that were previously difficult or impossible."

The paper states that the Johns Hopkins researchers will continue using the MSI Analysis System, Version 1.2 for detecting MSI in colorectal cancer, and they have adopted the LMR MSI Analysis System for endometrial, prostate and other non-GI cancers.

To learn more about the LMR MSI Analysis System, visit www.promega.com/LMRAnalysis

Promega Clinical Research Program

This study was supported in part by the Promega Clinical Research Program (PCRP), a global initiative that supports researchers using Promega technologies to advance clinical diagnostics. This is the first publication to result from a PCRP partnership, and seven more projects are currently benefitting from Promega products and expertise.