On April 20, 2022 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported that preclinical data demonstrating inhibition of CCNE1-amplified tumor growth in vivo by selective inhibition of PKMYT1 using RP-6306, a first-in-class small molecule candidate targeting PKMYT1, were published in Nature (Press release, Repare Therapeutics, APR 20, 2022, View Source [SID1234612597]). SNIPRx, Repare’s proprietary, genome-wide, CRISPR-based screening approach, was used to uncover CCNE1 amplification as synthetic lethal to PKMYT1 inhibition.

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The article, entitled "CCNE1 amplification is synthetic lethal with PKMYT1 kinase inhibition" is available at www.nature.com.

"RP-6306 is a first-in-class and highly selective PKMYT1 inhibitor, and these preclinical data show its ability to target CCNE1-amplfied tumors and profoundly inhibit tumor growth," said Michael Zinda, PhD, EVP and Chief Scientific Officer of Repare. "We are excited as this is another example of the power of genetic interaction screens to uncover new oncology drug targets, in this case in a cellular model of CCNE1 amplification. This led to the identification of a previously uncharacterized vulnerability to PKMYT1 inhibition that spurred the development of RP-6306 by Repare Therapeutics."

"We are thrilled that this work demonstrates both the power of our CRISPR-based SNIPRx platform to uncover novel synthetic lethal targets and Repare’s capacity to prosecute these targets resulting in first-in-class small molecule therapeutics," said Maria Koehler, MD, PhD, EVP and Chief Medical Officer of Repare. "It is uncommon that a new and validated target is published in a top tier journal concurrent with a launched clinical trial for a candidate drug on that target, and this speaks volumes about the innovative capacity of Repare and its collaborators."

Phase 1 clinical trials are currently evaluating RP-6306 as a monotherapy as well as in combination with gemcitabine for the treatment of molecularly selected advanced solid tumors. The Company recently initiated an additional Phase 1 MINOTAUR clinical trial of RP-6306 in combination with FOLFIRI also for the treatment of molecularly selected advanced solid tumors.

This work is the result of a long-standing collaboration between Repare Therapeutics and the laboratory of Daniel Durocher, PhD, a Senior Investigator at the Lunenfeld-Tanenbaum Research Institute, part of Sinai Health, in Toronto, Canada Dr. Durocher is also a Professor in the Department of Molecular Genetics at the University of Toronto. Work on CCNE1 in the Durocher laboratory was led by David Gallo, PhD, now a Senior Scientist at Repare and was financially supported by Repare Therapeutics and the Canadian Institutes of Health Research (CIHR).

About Repare Therapeutics’ SNIPRx Platform

Repare’s SNIPRx platform is a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines to identify novel and known synthetic lethal gene pairs and the corresponding patients who are most likely to benefit from the Company’s therapies based on the genetic profile of their tumors. Repare’s platform enables the development of precision therapeutics in patients whose tumors contain one or more genomic alterations identified by SNIPRx screening, in order to selectively target those tumors in patients most likely to achieve clinical benefit from resulting product candidates.

On April 20, 2022 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for cancer, reported that it will release its first quarter 2022 financial results on Wednesday, May 4, 2022 (Press release, Personalis, APR 20, 2022, View Source [SID1234612595]). In conjunction with the release, Personalis will host a conference call and webcast that day at 2:00 p.m. Pacific Time / 5:00 p.m. Eastern Time to discuss its financial results and recent highlights.

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Interested parties may access the live call via telephone by dialing (866) 220-8061 for domestic callers or (470) 495-9168 for international callers, using conference ID: 3187833. The live webinar of the call may be accessed by visiting the Events section of the company’s website at investors.personalis.com. A replay of the webinar will be available shortly after the conclusion of the call and will be archived on the company’s website.

On April 20, 2022 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported that data on its portfolio of skin cancer gene expression profile (GEP) tests will be shared via poster presentations during the 18th European Association of Dermato Oncology (EADO) Congress, being held virtually and in Seville, Spain, April 21-23, 2022 (Press release, Castle Biosciences, APR 20, 2022, View Source [SID1234612594]).

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The following e-Posters will be available for viewing on-site during the Congress in the ePoster area (ATRIO III) and also via the Congress platform, April 21-July 23, 2022.

Title: Incorporating the 31-gene expression profile test stratifies survival outcomes and leads to improved survival compared to clinicopathologic factors alone: A Surveillance, Epidemiology, and End Results (SEER) Program collaboration
Presenter: Sarah J. Kurley, Ph.D., Castle Biosciences, Inc.

Title: Independent multi-center cohort study confirms the performance of the prognostic 40-gene expression profile (40-GEP) test to classify risk of metastasis for high-risk cutaneous squamous cell carcinoma (cSCC) patients​
Presenter: Javier Cañueto, M.D., Ph.D., dermatologist at the University Hospital of Salamanca, Spain, associate professor at the University of Salamanca, associate researcher at the Institute for Biomedical Research of Salamanca (IBSAL) and postdoctoral researcher at the Cancer Research Institute of Salamanca (CSIC-USAL) University

Title: The current 23- and 35-gene expression profile (GEP) ancillary diagnostic testing workflow for difficult-to-diagnose melanocytic lesions increases the rate of actionable results to 99%
Presenter: Kelli L. Ahmed, Ph.D., Castle Biosciences, Inc.

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 the 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 Dec. 31, 2021, DecisionDx-Melanoma has been ordered 90,154 times for use with patients with cutaneous melanoma.

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 (low), 2A (moderate) or 2B (high) 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.

About Castle Biosciences’ Comprehensive Diagnostic Offering for Difficult-to-Diagnose Melanocytic Lesions

Castle Biosciences’ comprehensive diagnostic offering leverages the strengths of myPath Melanoma and DecisionDx DiffDx-Melanoma. These gene expression profile tests are designed to provide a highly accurate, objective result to aid dermatopathologists and dermatologists in characterizing difficult-to-diagnose melanocytic lesions. Of the approximately 2 million suspicious pigmented lesions biopsied annually in the United States, Castle estimates that approximately 300,000 of those cannot be confidently classified as either benign or malignant through traditional histopathology methods. For these cases, the treatment plan can also be uncertain. Obtaining highly accurate, objective ancillary testing can mean the difference between a path of overtreatment or the risk of undertreatment. Interpreted in the context of other clinical, laboratory and histopathologic information, myPath Melanoma and DecisionDx DiffDx-Melanoma are designed to reduce uncertainty and provide confidence for dermatopathologists and help dermatologists deliver more informed patient management plans.

On April 20, 2022 Humanigen, Inc. (Nasdaq: HGEN) ("Humanigen"), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm,’ reported a peer-reviewed publication in Leukemia, a leading oncology and hematology journal, entitled "GM-CSF disruption in CART cells modulates T cell activation and enhances CART cell anti-tumor activity (Press release, Humanigen, APR 20, 2022, View Source [SID1234612593])."

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This publication is a significant addition to the findings from a previous article in the leading hematology journal, blood, which demonstrated that neutralization of GM-CSF with lenzilumab (LENZ) was able to break the efficacy/toxicity linkage by reducing cytokine release syndrome (CRS) and neuroinflammation (ICANS) while enhancing CAR-T function.1 The Leukemia publication demonstrates that CRISPR/Cas9-mediated GM-CSF knockout in CAR-T cells directly ameliorates CAR-T cell early activation, reduces activation-induced cell death, and results in enhanced anti-tumor activity in vivo in a xenograft model.2

Enhancing CAR-T cell in vivo efficacy by using strategies to non-specifically stimulate CAR-T cell proliferation utilizing synthetic biology or combination therapy to edit exhaustion pathways or prevent apoptosis is an important goal and is the subject of substantial ongoing research. However, while this may improve CAR-T efficacy, it is often at the cost of an increase in important toxicities, such as CRS and ICANS. In contrast, these data published in Leukemia indicate that GM-CSFko CAR-T cells result in enhanced CAR-T cell proliferation and anti-tumor activity while being associated with a marked reduction in GM-CSF levels, which have been linked to CAR-T associated toxicities.

CAR-T therapies have resulted in significant advances for patients. However, for up to one-third of patients, toxicities such as severe ICANS and CRS occur, and tumor relapse is still a frequent occurrence.3 Currently, the widespread adoption of CAR-T therapy is limited, in part, by the requirement for treatment in centers that are experienced in managing the common toxicities of ICANS and CRS and by the financial and health burden that this creates. "CRS, ICANS, and tumor relapse remain challenges for physicians and patients treated with CAR-T therapy," said Saad Kenderian, M.B., Ch.B., hematologist at Mayo Clinic Cancer Center, an author of the Leukemia paper and the primary investigator for the SHIELD study (Study on How to Improve Efficacy and toxicity with Lenzilumab in DLBCL and other NHL patients treated with CAR-T therapy). He added, "They result in additional morbidity for patients, as well as significantly increased costs for healthcare providers. Treatments that can prevent ICANS and CRS while potentially improving CAR-T efficacy could address a critical unmet need."

This publication adds to the body of knowledge of GM-CSF depletion in CAR-T. The upcoming Phase 3 CAR-T study, known as SHIELD, will determine the efficacy and safety of prophylactic lenzilumab on the rates of ICANS, CRS, and CAR-T efficacy. "The SHIELD trial has been designed to build on the positive results from the ZUMA-19 study. The primary endpoint of SHIELD will focus on demonstrating a significant improvement in neurotoxicity associated with both Yescarta and Tecartus. We will also seek to explore the beneficial impact that lenzilumab may have CAR-T efficacy," stated Dale Chappell, M.D., MBA, Chief Scientific Officer, Humanigen.

About Lenzilumab

Lenzilumab is a proprietary Humaneered first-in-class monoclonal antibody that has been proven to neutralize GM-CSF, a cytokine of critical importance in the hyperinflammatory cascade, sometimes referred to as cytokine release syndrome, or cytokine storm, associated with COVID-19 and other indications. Lenzilumab binds to and neutralizes GM-CSF, potentially improving outcomes for patients hospitalized with COVID-19. Humanigen believes that GM-CSF neutralization with lenzilumab also has the potential to reduce the hyper-inflammatory cascade known as cytokine release syndrome common to chimeric antigen receptor T-cell (CAR-T) therapy and acute Graft versus Host Disease (aGvHD).

In CAR-T, lenzilumab successfully achieved the pre-specified primary endpoint at the recommended dose in a Phase 1b study (ZUMA-19) with Yescarta in which the overall response rate was 100% and no patient experienced severe cytokine release syndrome or severe neurotoxicity. Based on these results, Humanigen plans to test lenzilumab in a randomized, multicenter, potentially registrational, Phase 3 study ("SHIELD") to evaluate its efficacy and safety when combined with Yescarta and Tecartus CAR-T therapies in non-Hodgkin lymphoma. Lenzilumab will also be tested to assess its ability to prevent and/or treat acute Graft versus Host Disease (aGvHD) in patients undergoing allogeneic hematopoietic stem cell transplantation.

A study of lenzilumab is also underway for patients with chronic myelomonocytic leukemia (CMML) exhibiting RAS pathway mutations. This study builds on evidence from a Phase 1 study, conducted by Humanigen, that showed RAS mutations are associated with hyper-proliferative features, which may be sensitive to GM-CSF neutralization.

Lenzilumab is an investigational product and is not approved or authorized in any country.

On April 20, 2022 CytRx Corporation (OTCQB: CYTR) ("CytRx" or the "Company"), a biopharmaceutical innovator focused on research and development of life-saving cancer therapeutics, reported it has partnered with oncology development expert Gilad Gordon, MD to assist the Company in developing its next-generation LADR drugs toward first-in-human clinical trials (Press release, CytRx, APR 20, 2022, View Source [SID1234612592]).

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Dr. Gordon is President of ORRA Group, LLC, a consultancy focused on assisting companies in drug development efforts, particularly in oncology. Dr. Gordon brings 30 years of experience in the development of oncology therapeutics, having led clinical teams in multi-national Phase I through Phase III trials. Throughout his career, Dr. Gordon has participated in the filing of over 50 Investigational New Drug ("IND") applications, has had responsibility for hundreds of clinical trials in cancer and has been responsible for the final market approvals of approximately five cancer therapeutics that went on to help cancer patients. In addition, Dr. Gordon was a senior member of the management team that sold Inviragen, Inc. to Takeda Pharmaceutical Company Limited for $250 million and has been involved in raising more than $2 billion through IPOs, venture funding and other partnership programs.

CytRx CEO Dr. Stephen Snowdy commented:

"We are really excited to have someone with Dr. Gordon’s experience in developing cancer therapies working with us to move our next-generation LADR drugs closer to saving lives. CytRx is committed to moving these cancer assets toward IND filing as quickly and capital-efficiently as possible and is working hard to find the most expedient path possible. The difficult market environment has not impacted our confidence in LADR or our resolve to unlock shareholder value through advancement of our LADR-based drugs."

Dr. Gordon added:

"Globally, there are 17 million new cancer cases per year, and 10 million deaths due to cancer. Additional treatments for this disease are desperately needed. CytRx’s unique LADR backbone allows for the targeting of drugs to tumors, and subsequent concentration and release of drugs in the tumor, which is expected to reduce toxicity and increase efficacy. This elegant approach has the added benefit of being based on small molecules, which offers advantages in manufacturing and toxicity relative to large molecules, such as antibodies or liposomal particles. The first LADR drug, Aldoxorubicin, has provided validation of the LADR approach in multiple clinical trials, allowing several-fold higher dosing of doxorubicin than would be possible without the LADR backbone, and is in late-stage clinical trials for pancreatic cancer. Most importantly, the preclinical data on the next-generation LADR drugs is very impressive, and I look forward to helping guide these products through clinical testing and the regulatory process."

Dr. Gordon attended Harvard College and received his MD from Harvard Medical School. He is Board-certified in Internal Medicine and received his Master of Business Administration from the University of Washington. He is a Clinical Associate Professor of Medicine at the University of Colorado.