On April 22, 2021 Synthekine Inc., an engineered cytokine therapeutics company, reported a new agreement with Stanford University to license cytokine partial agonist programs for IL-10, IL-12 and IL-22 (Press release, Synthekine, APR 22, 2021, View Source [SID1234578375]). These programs augment a growing pipeline of selective cytokine partial agonists at Synthekine that is maturing toward clinical development.

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Most cytokines are pleiotropic and drive a range of signaling responses across multiple cell types, which limits their potential as therapeutics. Research conducted in the laboratory of Chris Garcia, PhD, a Howard Hughes Medical Institute Investigator and professor of structural biology at Stanford, has shown that IL-10, IL-12, and IL-22 can be tuned to achieve specific signaling. Modifying these cytokines enables selective activity to be directed to specific cell types for therapeutic benefit, often by decoupling efficacy from toxic effects driven by non-specific immune system activation. Synthekine plans to leverage discoveries in IL-12, recently published in the journal Cell, to develop potential treatments for cancer, and the discoveries in IL-10, recently published in the journal Science, and IL-22, recently published in the journal Immunity, to develop potential treatments for autoimmune disease.

"Synthekine was founded two years ago with several cytokine partial agonist programs based on the work from the Garcia Laboratory, and we have already moved two of those programs into IND enabling development," said Debanjan Ray, CEO of Synthekine. "Extending our license with Stanford allows us to bring in three new promising cytokine partial agonist programs that we believe have considerable potential in treating cancer and autoimmune disease."

On April 22, 2021 Candel Therapeutics, Inc., a late clinical stage biopharmaceutical company developing novel oncolytic viral immunotherapies, reported it has completed enrollment for its Phase 1 clinical trial in patients with newly diagnosed high-grade glioma to evaluate the safety and efficacy of CAN-2409 in combination with immune checkpoint inhibitor Opdivo (nivolumab) and standard of care radiation therapy, as well as temozolomide for patients with methylated MGMT promoters (Press release, Candel Therapeutics, APR 22, 2021, View Source [SID1234578374]). The trial enrolled 35 evaluable patients and is being conducted in collaboration with Bristol Myers Squibb Company, manufacturer of Opdivo, and separately the Adult Brain Tumor Consortium at Johns Hopkins University.

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"The addition of CAN-2409 to immune checkpoint inhibitor treatment has the potential to train lymphocytes to specifically recognize tumor neoantigens and to change the ‘cold’, immunosuppressive tumor microenvironment, thereby synergizing with lymphocyte activation induced by nivolumab resulting in tumor cell destruction," said Paul Peter Tak, M.D., Ph.D., President and Chief Executive Officer of Candel Therapeutics. "With a significant number of patients affected each year and limited treatment options available, there remains a critical need for effective therapies in high-grade glioma. It is our hope that CAN-2409 can create new, more effective options for this patient population, and we look forward to the readout from this study next year."

The primary endpoints of the study are safety and tolerability of this combined treatment regimen. Secondary endpoints include overall survival, progression free survival and immunological biomarkers. For more information about this study, please visit: www.clinicaltrials.gov (NCT03576612).

Opdivo is a registered trademark of Bristol Myers Squibb.

About CAN-2409

CAN-2409, previously known as gene-mediated cytotoxic immunotherapy (GMCI), Candel’s most advanced oncolytic viral immunotherapy candidate, is a replication-deficient adenovirus that delivers the herpes simplex virus thymidine kinase (HSV-tk) gene to cancer cells. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic metabolite that kills nearby cancer cells. The intra-tumoral administration results in the release of tumor-specific neoantigens in the microenvironment, thereby training the immune system to recognize these antigens. The activated effector T cells have the potential to migrate to distant, uninjected metastases for broad anti-tumor activity. At the same time, the adenoviral capsid protein elicits a strong pro-inflammatory signal in the tumor microenvironment. This adjuvant effect helps create a better immune response against the tumor neoantigens released locally. This dual mechanism of antigen unmasking and immune activation may enable CAN-2409 to generate a powerful and lasting attack against a variety of the patient’s tumor-associated neoantigens, minimizing the possibility for antigen escape and tolerance development.

Because of its versatility, CAN-2409 may have the potential to treat a broad range of solid tumors. Combination activity with standard of care radiation therapy, surgery, immune checkpoint inhibitors

(ICI) and chemotherapy has already been shown in several preclinical and clinical settings. Candel has previously published preclinical data that supports combination of CAN-2409 with ICI. In a mouse model of glioblastoma unresponsive to ICI, addition of CAN-2409 was shown to modulate the immunosuppressive, unresponsive tumor microenvironment, resulting in a synergistic effect in vivo, with significantly improved survival in mice treated with CAN-2409 and ICI combination. Furthermore, CAN-2409 presents a favorable tolerability profile. More than 700 patients have been dosed to date, supporting the potential for combination with other therapeutic strategies without inordinate concern of overlapping adverse events. Currently, Candel is evaluating the effects of treatment with CAN-2409 for brain, prostate, lung, and pancreatic cancers in clinical trials.

On April 22, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported participation in the Dermatology Nurses’ Association 2021 Annual Convention (Press release, Castle Biosciences, APR 22, 2021, View Source [SID1234578373]). Castle presented posters highlighting each of the company’s three skin cancer gene expression profile (GEP) tests.

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Poster information is as follows:

DecisionDx-Melanoma:

The poster is entitled, "31-gene expression profiling improves risk stratification in patients with T1 cutaneous melanoma."

DecisionDx-Melanoma is Castle’s 31-gene expression profile test that uses an individual patient’s tumor biology to predict risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node (SLN) positivity, independent of traditional staging factors.

Study methods and findings:

Nearly 70% of melanomas are diagnosed with tumor thickness that is less than or equal to 1.0 mm (T1 tumors), and recurrence-free survival (RFS) is generally good among these patients. However, up to 15% of patients with T1 tumors may experience a recurrence. Moreover, due to the large number of patients with T1 tumors, 27-30% of melanoma-related deaths occur in patients originally diagnosed with a T1 tumor, suggesting better identification of T1 patients at high risk of recurrence or metastasis is needed.
DecisionDx-Melanoma is designed to classify a patient’s recurrence risk as low (Class 1: Class 1A lowest) or high (Class 2: Class 2B highest) and has been validated in multiple prospective and retrospective studies.
Univariate analysis of the study data shows DecisionDx-Melanoma to be a stronger predictor of RFS than SLN status.
Multivariable analysis shows DecisionDx-Melanoma to be a strong, independent predictor of RFS.
With Class 2B RFS status similar to SLN positive status, Class 2B patients warrant follow-up strategies similar to SLN positive patients.
DecisionDx-SCC:

The poster is entitled, "Clinical utility of the 40-gene expression profile (40-GEP) for improved patient management decisions and disease related outcomes when combined with current clinicopathological risk factors for cutaneous squamous cell carcinoma (cSCC): Case Series."

DecisionDx-SCC is Castle’s prognostic 40-gene expression profile test for patients diagnosed with high-risk cutaneous squamous cell carcinoma (SCC) designed to use a patient’s tumor biology to predict individual risk of metastasis for patients with SCC and one or more risk factors.

Study methods and findings:

Two SCC cases were presented that highlight DecisionDx-SCC’s utility in stratifying risk in SCC.
The cases were very similar at diagnosis, both presenting with a history of immunosuppression along with identical staging (T2a per Brigham and Women’s Hospital staging; T1 per American Joint Committee on Cancer staging), but had divergent outcomes:
Case 1 did not recur, despite incomplete resection.
Case 2 developed local recurrence and regional metastasis, and died from SCC, despite clear surgical margins, radiation and chemotherapy treatments.
Subsequent DecisionDx-SCC test results yielded risk level assignments that correlated with the two patients’ outcomes:
Case 1 had a retrospective low-risk (Class 1) DecisionDx-SCC result.
Case 2 had a highest-risk (Class 2B) DecisionDx-SCC result.
The authors concluded that incorporating DecisionDx-SCC as a prognostic factor with traditional clinicopathological risk factors can improve stratification of high-risk SCC patients with at least one risk factor, thereby informing risk-appropriate management strategies.
DecisionDx DiffDx-Melanoma:

The poster is entitled, "Development, validation, and clinical utility of the 35-gene expression profile test for use as an adjunctive melanoma diagnostic tool."

DecisionDx DiffDx-Melanoma is designed to aid dermatopathologists in characterizing difficult-to-diagnose melanocytic lesions.

Study methods and findings:

DecisionDx DiffDx-Melanoma was developed using artificial intelligence methods trained on 200 benign nevi and 216 melanomas to select a panel of 32 discriminant and 3 control genes.
The test’s ability to differentiate accurately between benign and malignant pigmented skin lesions was characterized.
The test provides a high technical success rate at 96.6% with a modest intermediate-risk zone of 3.6%.
The analytical validity data of the DecisionDx DiffDx-Melanoma test demonstrates high precision as an indication of technical success.
Dermatopathologists utilized the DecisionDx DiffDx-Melanoma result to refine their diagnoses and their diagnostic confidence increased by 51%.
Dermatologists utilized the DecisionDx DiffDx-Melanoma result, which in the majority of responses, led to altered treatment plans in agreement with the DecisionDx DiffDx-Melanoma result.
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 sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 5,700 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. To predict likelihood of sentinel lymph node positivity, the Company utilizes its proprietary algorithm, i31-GEP, to produce an integrated test result. i31-GEP is an artificial intelligence-based neural network algorithm (independently validated in a cohort of 1,674 prospective, consecutively tested patients with T1-T4 cutaneous melanoma) that integrates the DecisionDx-Melanoma test result with the patient’s traditional clinicopathologic features. 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. Through December 31, 2020, DecisionDx-Melanoma has been ordered more than 68,920 times for use in patients with cutaneous melanoma.

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

About DecisionDx DiffDx-Melanoma

DecisionDx DiffDx-Melanoma is designed to aid dermatopathologists in characterizing difficult-to-diagnose melanocytic lesions. Of the approximately 2 million suspicious pigmented lesions biopsied annually in the U.S., Castle estimates that approximately 300,000 of those cannot be confidently classified as either benign or malignant through traditional histopathology methods. DecisionDx DiffDx-Melanoma classifies these lesions as: benign (gene expression profile suggestive of benign neoplasm); intermediate-risk (gene expression profile cannot exclude malignancy); or malignant (gene expression profile suggestive of melanoma). Interpreted in the context of other clinical, laboratory and histopathologic information, DecisionDx DiffDx-Melanoma is designed to add diagnostic clarity and confidence for dermatopathologists while helping dermatologists deliver more informed patient management plans.

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

About DecisionDx-SCC

DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous squamous cell carcinoma metastasis for patients with one or more risk factors. The test result, in which patients are stratified into a Class 1, 2A or 2B risk category, predicts individual metastatic risk to inform risk-appropriate management.

Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that integrating DecisionDx-SCC with current prognostic methods can add positive predictive value to clinician decisions regarding staging and management.

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

On April 22, 2021 Aptorum Group Limited (Nasdaq: APM, Euronext Paris: APM) ("Aptorum Group" or "Aptorum"), a clinical-stage biopharmaceutical company, through its affiliate, reported that it has entered into a material transfer and option agreement ("Agreement") with Yale University ("Yale") to evaluate a group of preclinical stage novel immunomodulators (Press release, Aptorum, APR 22, 2021, View Source [SID1234578372]). The novel immunomodulators may potentially target autoimmune and oncology diseases, including but not limited to, rheumatoid arthritis, lupus and sclerosis, as well as a variety of cancers, all subject to further preclinical development and testing. Aptorum also obtained an exclusive option to in-license the novel immunomodulators and its affiliated intellectual property rights including its patent rights and know-how, based on licensing terms pursuant to a binding term sheet incorporated into the Agreement.

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Under the arrangement, Aptorum will be responsible for assessing Yale’s originally developed novel immunomodulators against lupus, arthritis, inflammatory bowel diseases, neurodegenerative diseases or other oncology indications. Upon exercising its option to license, Aptorum will undertake to develop and commercialize one or more of these novel immunomodulators, as supported by Yale.

Mr. Ian Huen, Chief Executive Officer of Aptorum Group, commented: "Aptorum is delighted to partner with Yale to validate and develop its novel class of immunomodulators. Aptorum believes that these immunomodulators have the potential to advance first-in-class drug discovery and development of such drugs for potential autoimmune and oncology diseases in particular. For example, it has been widely reported that COVID-19 infections often trigger a cytokine storm in patients leading to undesirable and often fatal autoiummune reactions1 and we will also explore the potential applications of the immunomodulators for the treatment of these cytokine storms. Through this initiative, we are looking forward to strategically expanding our development footprint in the treatment of those diseases, which have other potential applications such as in oncology and infectious diseases which are already core focuses of our company."

On April 22, 2021 ITM AG reported that the successful close of a convertible loan financing totaling EUR 90 million (USD 109 million) led by Petrichor Healthcare Capital Management with participation of additional undisclosed investors (Press release, ITM Isotopen Technologien Munchen, APR 22, 2021, View Source [SID1234578371]). The proceeds will support the expansion of ITM’s precision oncology pipeline as well as fund late-stage development and market access activities for lead candidate, n.c.a. 177Lu-Edotreotide, currently in a phase III trial in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Under the terms of the agreement, the loan will convert into shares of ITM in the event of certain future financial or other corporate development transactions. Further details of the financing were not disclosed.

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"This funding represents our commitment to being at the forefront of demonstrating the therapeutic potential of Targeted Radionuclide Therapy and reflects our ambition to translate our leadership as a global radioisotope provider into developing innovative radiopharmaceuticals to meet the needs of patients with difficult-to-treat tumors. The investment from Petrichor and the syndicate recognizes our clinical and corporate achievements to date and enables us to further leverage the full potential of nuclear medicine for cancer patients," commented Steffen Schuster, Chief Executive Officer of ITM.

In conjunction with the financing, Tadd Wessel, Founder and Managing Partner at Petrichor, will join ITM’s supervisory board. He brings more than 20 years of experience in the healthcare financing sector and was formerly a Managing Director at OrbiMed Advisors, where he led the build-out of the healthcare special situations and structured finance business.

Mr. Wessel added: "ITM has established itself as a dominant global provider of therapeutic radioisotopes. We expect the company’s isotope business to benefit from tremendous growth of targeted radiotherapy in the years ahead, while serving as a platform for ITM’s deep pipeline of precision oncology Targeted Radionuclide Therapies and companion diagnostics. Targeted radiotherapy has demonstrated immense success to date, and we expect the drug class to continue to gain recognition as one of the most promising areas within precision oncology. We believe that ITM’s unparalleled expertise and technological capabilities are evidenced by their market leadership, and we look forward to supporting the team in their pursuit of better patient outcomes."

ITM, founded in 2004, is a company built on longstanding experience in the production and supply of high-quality medical radioisotopes for cancer treatment and diagnosis with an established global supply network. The company has forward-integrated to develop Targeted Radionuclide Diagnostics and Therapies designed to provide medical benefit for difficult-to-treat cancer indications.