N-Myc

Study is the first to identify malignant cells responsible for relapse in high-risk neuroblastoma PHILADELPHIA, Aug. 15, 2024 /PRNewswire/ -- Researchers at Children's Hospital of Philadelphia (CHOP) announced a significant breakthrough in understanding chemotherapy resistance in high-risk neuroblastoma, a common and potentially deadly childhood cancer arising within the peripheral nervous system. The study marks the first time that researchers identified malignant cells responsible for relapse in neuroblastoma and offers insights for potential new therapeutic targets. The findings were published recently in the journal Cancer Discovery. In the United States, about 800 new cases of neuroblastoma are diagnosed each year, more often in boys. The average age of diagnosis is about 18 months but occasionally the disease is seen in teens and young adults. Neuroblastoma has a high mortality rate and despite extensive studies, the malignant cells responsible for relapse were not well understood until this research. This study is part of research conducted by the Human Tumor Atlas Network (HTAN), a National Cancer Institute (NCI) Moonshot initiative led by Kai Tan, PhD, an investigator in the Center for Childhood Cancer Research at CHOP, and a multi-institutional NCI Program Project Grant (PPG) focused on neuroblastoma and led by John M. Maris, MD, a study co-author and pediatric oncologist at CHOP. "This study is a major step forward in identifying why neuroblastoma is so difficult to cure," said Maris, who also holds the Giulio D'Angio Chair in Neuroblastoma Research. "Targeting specific cells and pathways responsible for relapse empowers us to chart a new path forward, allowing us to develop potentially safe and effective treatments for children and families battling this aggressive cancer." The CHOP research team employed advanced single nucleus RNA sequencing (snRNA-seq) and bulk whole genome sequencing techniques to analyze the genetic and transcriptional profiles of tumor samples from 20 pediatric patients with high-risk neuroblastoma who were treated between 2007 and 2022. The samples included matched diagnostic biopsies and definitive surgery specimens obtained after several cycles of induction chemotherapy. "HTAN played a crucial role in generating the powerful multi-omics dataset that led to the hypothesis we tested in this paper," said Tan, who is also a professor in the Department of Pediatrics at CHOP and spearheads CHOP's participation in the HTAN. "It supports the broader application of the identified therapeutic targets and resistance mechanisms in high-risk neuroblastoma." The investigators discovered and validated the fact that neuroblastoma can evade chemotherapy by becoming dormant and not constantly multiplying—a major hallmark of cancer. Thus, these "non-cycling" cells are resistant to chemotherapy, which is designed to kill cells that are actively multiplying. These "persister cells" can hide in the body for months or even years and see a relapse when they later awaken. To validate their findings and enhance the analysis, the researchers leveraged independent post-induction chemotherapy data generated by other groups in the HTAN. By assessing the primary study's findings within the context of other datasets, the researchers ensured consistency and reliability in the transcriptional subtypes they identified. For example, researchers were able to study the expression level of the MYCN gene and its relationship to the transcriptional subtypes. This provided several insights into the biology of neuroblastoma and offered promising new therapies. As a result, Maris noted that the NCI-funded neuroblastoma PPG is actively pursuing research and that several immunotherapeutic strategies to eliminate persister cells are already being tested. "This research could have far-reaching implications beyond neuroblastoma, as it enhances our understanding of chemotherapy resistance mechanisms," said Liron Grossmann, MD, MSc, the study's lead author, who managed the research during his Hematology-Oncology fellowship at CHOP, and is currently a Senior Attending Physician at Sheba Medical Center in Israel. "We've gained invaluable insights that can inform new approaches for various cancers, potentially improving treatment outcomes and reducing relapse rates across a broad spectrum of malignancies." The study was supported by Human Tumor Atlas Network U2C CA233285 and the National Cancer Institute (NCI) grants R35 CA220500, P01 CA217959, and K08 CA266914. This work was also supported by the Sheba Medical Center Physician-Scientist Program, the Giulio D'Angio Endowed Chair, the Richard & Sheila Sanford Endowed Chair and the Patricia Brophy Endowed Chair. Grossmann et al. "Identification and characterization of chemotherapy resistant high-risk neuroblastoma persister cells." Cancer Discovery. Online July 31, 2024. DOI: 10.1158/2159-8290.CD-24-0046. About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit . Contact: Jennifer Lee Children's Hospital of Philadelphia (267) 426-6084 [email protected] SOURCE Children's Hospital of Philadelphia

IND clearance achieved for MRT-6160, a VAV1-directed MGD in development for systemic and neurological autoimmune diseases; on track to initiate Phase 1 SAD/MAD study this summer with initial clinical data expected in Q1 2025 Ongoing Phase 1/2 Study of MRT-2359 for MYC-driven solid tumors demonstrated a favorable safety and pharmacodynamic profile at 0.5 mg with a 21 days on/7 days off schedule; dosing ongoing at 0.75 mg using a 21/7 schedule; final determination of recommended Phase 2 dose and updated clinical results anticipated in H2 2024 Achieved first program and financial milestones from strategic research collaboration with Roche Strong cash position expected to fund operations into H1 2027 and through multiple anticipated clinical readouts including from proof-of-concept patient studies for MRT-2359, MRT-6160, and MRT-8102 BOSTON, Aug. 08, 2024 (GLOBE NEWSWIRE) -- Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, today reported business highlights and financial results for the second quarter that ended June 30, 2024. “The IND clearance of our VAV1-directed MGD MRT-6160 represents a major corporate milestone for Monte Rosa, signifying what we believe to be the first clinical-stage, rationally designed MGD for a non-oncology indication,” said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. “Our MRT-2359 program for MYC-driven solid tumors is in an ongoing Phase 1/2 study and we look forward to announcing the recommended Phase 2 dose, sharing updated clinical efficacy and safety results from the dose escalation arm of the trial, and initiating enrollment of our Phase 2 expansion cohorts in the second half of the year. Our second immunology/inflammation program, MRT-8102, a NEK7-directed MGD targeting diseases driven by IL-1β and the NLRP3 inflammasome, continues to advance and we expect to submit an IND application in the first half of next year. Our strategic collaboration with Roche has been progressing rapidly, and we are very pleased to announce today that we have reached our first set of research milestones, which we believe further validates the productivity of our QuEEN Discovery Engine. Our strong balance sheet, augmented by our recent financing, is expected to provide cash runway into H1 2027, funding the Company through multiple anticipated milestones including proof-of-concept readouts for our three lead programs.” RECENT HIGHLIGHTS MRT-2359, GSPT1-directed MGD for MYC-driven solid tumors Monte Rosa continues to evaluate MRT-2359 in a Phase 1/2 clinical trial in MYC-driven solid tumors (NCT05546268). In June 2024, the Company announced that it had obtained encouraging initial safety and pharmacodynamic data from the 0.5 mg dose using the 21 days on, 7 days off regimen. This regimen represents dosing of MRT-2359 twice as frequently per cycle compared to the 5 days on, 9 days off regimen previously evaluated in this study. Based on the favorable safety assessment for the 0.5 mg dose, the Company continues to evaluate a higher 0.75 mg, 21 days on, 7 days off dose cohort. In the second half of the year, Monte Rosa expects to make a final determination of the MRT-2359 recommended Phase 2 dose, share updated clinical activity and safety results from the dose escalation arm of the trial, and initiate enrollment of MRT-2359 Phase 2 expansion cohorts. MRT-6160, VAV1-directed MGD for systemic and neurological autoimmune/inflammatory diseases Monte Rosa today announced that its Investigational New Drug (IND) submission for MRT-6160 has been accepted by the U.S. Food and Drug Administration (FDA). Initiation of a Phase 1 single ascending dose/multiple ascending dose (SAD/MAD) study is expected this summer and initial clinical results are anticipated in Q1 2025.In July, Monte Rosa reported the publication of a review article titled, VAV1 as a putative therapeutic target in autoimmune and chronic inflammatory diseases, co-authored by Prof. Dr. Markus F. Neurath, Friedrich-Alexander-University Erlangen-Nürnberg, and Prof. Leslie J. Berg, University of Colorado School of Medicine, in the peer-reviewed journal Trends in Immunology, a Cell Press journal. The publication highlights how novel approaches targeting VAV1 have therapeutic potential in T and B-cell-mediated autoimmune and chronic inflammatory diseases.In June, Monte Rosa presented preclinical data at the EULAR 2024 conference demonstrating that MRT-6160 inhibited disease progression, pro-inflammatory cytokines, and autoantibody production in the collagen-induced arthritis murine model of rheumatoid arthritis.In May, Monte Rosa presented preclinical data at Digestive Disease Week 2024 demonstrating that MRT-6160 inhibited colitis disease progression and colon inflammation, lowered inflammatory mucosal cytokines, and reduced expression of IBD-associated genes in a T-cell transfer murine model of colitis. MRT-8102, NEK7-directed MGD for inflammatory diseases driven by IL-1β and the NLRP3 inflammasome In March, Monte Rosa announced the initiation of IND-enabling studies for MRT-8102, a first-in-class NEK7-directed MGD for the treatment of inflammatory diseases driven by interleukin-1β (IL-1β) and the NLRP3 inflammasome, critical elements of the inflammatory process. MRT-8102 has demonstrated highly favorable central nervous system (CNS) exposure and degradation in a study in non-human primates, supporting its potential development in neurologic indications and obesity, in addition to potential use in gout, pericarditis, and other peripheral inflammatory conditions. The Company is evaluating applications across multiple inflammatory disorders.Monte Rosa expects to submit an IND application for MRT-8102 in H1 2025. CDK2 and Cyclin E1-directed MGD programs In May, Monte Rosa announced a new discovery program for CCNE1 (Cyclin E1)-directed MGDs for the treatment of CCNE1-amplified tumors. CCNE1, a key component of the cell cycle and a known driver of many cancers, is generally considered an undruggable target by conventional modalities.Monte Rosa is progressing both programs to development candidate nominations and expects to nominate a development candidate for the CDK2-directed MGD program by year-end. Additional Corporate Updates Monte Rosa announced today that it achieved pre-specified research milestones and earned milestone payments under its strategic collaboration and licensing agreement with Roche. In October 2023, Monte Rosa entered into a strategic collaboration and licensing agreement with Roche to discover and develop MGDs against targets in cancer and neurological diseases. Under the terms of the agreement, Monte Rosa received an upfront payment of $50 million and is eligible to receive future preclinical, clinical, commercial, and sales milestone payments that could exceed $2 billion, as well as tiered royalties.In May, the Company announced an underwritten public offering providing gross proceeds of approximately $100 million.In May, Monte Rosa announced three leadership team promotions: Sharon Townson, Ph.D., to Chief Scientific Officer; Phil Nickson, Ph.D., J.D., to Chief Business and Legal Officer; and Jennifer Champoux to Chief Operating Officer. ANTICIPATED MILESTONES Announce the recommended Phase 2 dose for the MRT-2359 Phase 1/2 study and report Phase 1 clinical activity and safety results in H2 2024. The Company also plans to initiate the Phase 2 portion of the study before year-end. The Company is evaluating Phase 2 expansion cohorts in high-prevalence c-MYC-driven tumors, including hormone receptor-positive breast cancer and prostate cancer, as well as tumor types and patient populations driven by L- and N-MYC including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and solid tumors with amplifications of L- and N-MYC.Initiate a Phase 1 SAD/MAD study with MRT-6160 in healthy volunteers in mid-2024; report results from the Phase 1 study in Q1 2025. Monte Rosa expects to subsequently initiate proof-of-concept (POC) studies in autoimmune/inflammatory diseases, including ulcerative colitis and rheumatoid arthritis, with additional potential POC studies in dermatology, rheumatology, and neurology indications.Submit an IND application for MRT-8102 in H1 2025.Nominate a development candidate for the CDK2 preclinical program in 2024. SECOND QUARTER 2024 FINANCIAL RESULTS Collaboration Revenue: Collaboration revenue for the second quarter of 2024 was $4.7 million, compared with $0 during the same period in 2023. Collaboration revenue represents revenue recorded under the Roche License and Collaboration agreement. Research and Development (R&D) Expenses: R&D expenses for the second quarter of 2024 were $28.1 million, compared to $29.1 million during the same period in 2023. R&D expenses were driven by the successful achievement of key milestones in our R&D organization, including the continuation of the MRT-2359 clinical study, the progression and growth of our preclinical pipeline, the preparation of MRT-6160 to enter the clinic, and the continued development of the Company’s QuEEN™ discovery engine. Non-cash stock-based compensation constituted $2.6 million of R&D expenses for Q2 2024, compared to $2.3 million in the same period in 2023. General and Administrative (G&A) Expenses: G&A expenses for the second quarter of 2024 were $9.3 million compared to $8.1 million during the same period in 2023. The increase in G&A expenses resulted from increased headcount, stock-based compensation expense, and fees paid to consultants to support growth and operations. G&A expenses included non-cash stock-based compensation of $1.9 million for the second quarter of 2024, compared to $1.9 million for the same period in 2023. Net Loss: Net loss for the second quarter of 2024 was $30.3 million, compared to $32.0 million for the first quarter of 2024. Cash Position and Financial Guidance: Cash, cash equivalents, restricted cash, and marketable securities as of June 30, 2024, were $267.1 million, compared to cash, cash equivalents, restricted cash, and marketable securities of $197.8 million as of March 31, 2024. The Company expects its cash and cash equivalents to be sufficient to fund planned operations and capital expenditures into the first half of 2027. About MRT-2359MRT-2359 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that induces the interaction between the E3 ubiquitin ligase component cereblon and the translation termination factor GSPT1, leading to the targeted degradation of GSPT1 protein. The MYC transcription factors (c‑MYC, L-MYC and N-MYC) are well-established drivers of human cancers that maintain high levels of protein translation, which is critical for uncontrolled cell proliferation and tumor growth. Preclinical studies have shown this addiction to MYC-induced protein translation creates a dependency on GSPT1. By inducing degradation of GSPT1, MRT-2359 is designed to exploit this vulnerability, disrupting the protein synthesis machinery, leading to anti-tumor activity in MYC-driven tumors. About MRT-6160MRT-6160 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader of VAV1, which in preclinical studies has shown deep degradation of its target with no detectable effects on other proteins. VAV1, a Rho-family guanine nucleotide exchange factor, is a key signaling protein downstream of both the T- and B-cell receptors. VAV1 expression is restricted to blood and immune cells, including T and B cells. Preclinical studies have shown that targeted degradation of VAV1 protein via an MGD modulates both T- and B-cell receptor-mediated activity. This modulation is evident both in vitro and in vivo, demonstrated by a significant decrease in cytokine secretion, proteins vital for maintaining autoimmune diseases. Moreover, VAV1-directed MGDs have shown promising activity in preclinical models of autoimmune diseases and thus have the potential to provide therapeutic benefits in multiple systemic and neurological autoimmune indications, such as inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and dermatological disorders. Preclinical studies have demonstrated that MRT-6160 can inhibit disease progression in several in vivo autoimmunity models. About MRT-8102MRT-8102 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that targets NEK7 for the treatment of inflammatory diseases driven by IL-1β and the NLRP3 inflammasome. NEK7 has been shown to be required for NLRP3 inflammasome assembly, activation and IL-1β release both in vitro and in vivo. Aberrant NLRP3 inflammasome activation and the subsequent release of active IL-1β and interleukin-18 (IL-18) has been implicated in multiple inflammatory disorders, including gout, cardiovascular disease, neurologic disorders including Parkinson’s disease and Alzheimer’s disease, ocular disease, diabetes, obesity, and liver disease. In a non-human primate model, MRT-8102 was shown to potently, selectively, and durably degrade NEK7, and resulted in near-complete reductions of IL-1β models following ex vivo stimulation of whole blood. MRT-8102 has shown a favorable profile in non-GLP toxicology studies. About Monte RosaMonte Rosa Therapeutics is a clinical-stage biotechnology company developing highly selective molecular glue degrader (MGD) medicines for patients living with serious diseases in the areas of oncology, autoimmune and inflammatory diseases, and more. MGDs are small molecule protein degraders that have the potential to treat many diseases that other modalities, including other degraders, cannot. Monte Rosa’s QuEEN™ (Quantitative and Engineered Elimination of Neosubstrates) discovery engine combines AI-guided chemistry, diverse chemical libraries, structural biology, and proteomics to identify degradable protein targets and rationally design MGDs with unprecedented selectivity. The QuEEN discovery engine enables access to a wide-ranging and differentiated target space of well-validated biology across multiple therapeutic areas. Monte Rosa has developed the industry’s leading pipeline of MGDs, which spans oncology, autoimmune and inflammatory disease and beyond, and has a strategic collaboration with Roche to discover and develop MGDs against targets in cancer and neurological diseases previously considered impossible to drug. For more information, visit www.monterosatx.com. Forward-Looking Statements This communication includes express and implied “forward-looking statements,” including forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements that are not historical facts and in some cases, can be identified by terms such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. Forward-looking statements contained herein include, but are not limited to, statements about our ability to grow our product pipeline, statements around the Company’s QuEENTM discovery engine and the Company’s view of its potential to identify degradable protein targets and rationally design MGDs with unprecedented selectivity, statements around the productivity of the QuEEN discovery engine and the potential of the Company’s MGDs against a broad spectrum of targets, statements about the advancement and timeline of our preclinical and clinical programs, pipeline and the various products therein, including (i) our ongoing clinical development of our GSPT1 degrader referred to as MRT-2359, including our expectations for the nature, significance, and timing for our disclosure of any updated data from our Phase 1/2 clinical trial of MRT-2359 in MYC-driven solid tumors in the second half of 2024, timing for our identification and any disclosure of a recommended Phase 2 dose for MRT-2359 in the second half of 2024, and timing of enrollment of Phase 2 expansion cohorts in the second half of 2024, (ii) the ongoing development of our VAV1-directed degrader, referred to as MRT-6160, and the planned Phase 1 SAD/MAD study in the summer of 2024 with initial clinical data expected in the first quarter of 2025 and our expectations regarding the potential clinical benefit for this program, (iii) the ongoing development of our NEK7-directed MGD, referred to as MRT-8102, and our expectations around its potential across neurologic indications amongst others, as well as potential use in gout, pericarditis, and other peripheral inflammatory conditions, including our expectations to submit an IND to the FDA in the first quarter of 2025, and our statements around multiple anticipated clinical readouts, including results from proof-of-concept patient studies for MRT-2359, MRT-6160, and MRT-8102, advancement and application of our pipeline, including identification and the timing thereof of a development candidate for CDK2 until the end of 2024, statements around the advancement and application of our platform, statements concerning our expectations regarding our ability to nominate and the timing of our nominations of additional targets, product candidates, and development candidates, statements regarding regulatory filings for our development programs, including the planned timing of such regulatory filings, such as IND applications, and potential review by regulatory authorities, our use of capital, expenses and other financial results in the future, availability of funding for existing programs, ability to fund operations into the first half of 2027, as well as our expectations of success for our programs, strength of collaboration relationships and the strength of our financial position, among others. By their nature, these statements are subject to numerous risks and uncertainties, including those risks and uncertainties set forth in our most recent Annual Report on Form 10-K for the year ended December 31, 2023, filed with the U.S. Securities and Exchange Commission on March 14, 2024, and any subsequent filings, that could cause actual results, performance or achievement to differ materially and adversely from those anticipated or implied in the statements. You should not rely upon forward-looking statements as predictions of future events. Although our management believes that the expectations reflected in our statements are reasonable, we cannot guarantee that the future results, performance, or events and circumstances described in the forward-looking statements will be achieved or occur. Recipients are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date such statements are made and should not be construed as statements of fact. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, any future presentations, or otherwise, except as required by applicable law. Certain information contained in these materials and any statements made orally during any presentation of these materials that relate to the materials or are based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party studies, publications, surveys and other data to be reliable as of the date of these materials, we have not independently verified, and make no representations as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of our internal estimates or research and no reliance should be made on any information or statements made in these materials relating to or based on such internal estimates and research. Consolidated Balance Sheets (in thousands, except share amounts) (Unaudited) June 30, December 31, 2024 2023 Assets Current assets: Cash and cash equivalents $108,847 $128,101 Marketable securities 153,358 104,312 Accounts receivable 9,000 — Other receivables 842 505 Prepaid expenses and other current assets 5,849 3,294 Total current assets 277,896 236,212 Property and equipment, net 33,250 33,803 Operating lease right-of-use assets 27,893 28,808 Restricted cash, net of current 4,866 4,580 Other long-term assets 209 352 Total assets $344,114 $303,755 Liabilities and stockholders’ equity Current liabilities: Accounts payable $6,473 $11,152 Accrued expenses and other current liabilities 12,759 14,600 Current deferred revenue 19,645 17,678 Current portion of operating lease liability 3,471 3,162 Total current liabilities 42,348 46,592 Deferred revenue, net of current 33,596 32,323 Defined benefit plan liability 2,614 2,713 Operating lease liability 40,885 42,877 Total liabilities 119,443 124,505 Commitments and contingencies Stockholders’ equity Common stock, $0.0001 par value; 500,000,000 shares authorized, 61,333,597 shares issued and 61,328,282 shares outstanding as of June 30, 2024; and 50,154,929 shares issued and 50,140,233 shares outstanding as of December 31, 2023 6 5 Additional paid-in capital 655,501 547,857 Accumulated other comprehensive loss (2,670) (2,724) Accumulated deficit (428,166) (365,888) Total stockholders’ equity 224,671 179,250 Total liabilities and stockholders’ equity $344,114 $303,755 Consolidated Statements of Operations and Comprehensive Income (Loss)(In thousands, except share and per share amounts) Three months endedJune 30, Six months endedJune 30, 2024 2023 2024 2023 Collaboration revenue $4,695 $— $5,759 $— Operating expenses: Research and development 28,055 29,076 55,081 55,831 General and administrative 9,282 8,145 18,267 15,649 Total operating expenses 37,337 37,221 73,348 71,480 Loss from operations (32,642) (37,221) (67,589) (71,480)Other income (expense): Interest income, net 2,637 2,302 5,079 4,739 Foreign currency exchange gain (loss), net (53) (93) 567 (178)Gain on disposal of fixed assets — 24 — 24 Loss on sale of marketable securities — — — (131)Total other income 2,584 2,233 5,646 4,454 Net loss before income taxes $(30,058) $(34,988) $(61,943) $(67,026)Provision for income taxes (252) (190) (335) (190)Net loss $(30,310) $(35,178) $(62,278) $(67,216)Net loss per share attributable to common stockholders—basic and diluted $(0.43) $(0.71) $(0.95) $(1.36)Weighted-average number of shares outstanding used in computing net loss per common share—basic and diluted 71,233,992 49,431,922 65,695,095 49,389,931 Comprehensive loss: Net loss $(30,310) $(35,178) $(62,278) $(67,216)Provision for pension benefit obligation 35 14 70 28 Unrealized gain (loss) on available-for-sale securities (12) (261) (16) 84 Comprehensive loss $(30,287) $(35,425) $(62,224) $(67,104) InvestorsAndrew Funderburkir@monterosatx.com MediaCory Tromblee, Scient PRmedia@monterosatx.com

TAIPEI, July 11, 2024 /PRNewswire/ -- Senhwa Biosciences, Inc. (TPEx: 6492), announced IND Submission to US FDA for the Phase I/II study of Silmitasertib (CX-4945) in combination with chemotherapy in children and young adults with relapsed refractory solid tumors. This investigator-initiated trial (IIT) will be conducted by the Penn State Health Children's Hospital and the prestigious Beat Childhood Cancer Research Consortium, a group of over 50 universities and children's hospitals, based at Penn State College of Medicine in Hershey, Pa., that offers a worldwide network of pediatric cancer clinical trials. The funding is sponsored by the Four Diamonds Foundation, with Senhwa Biosciences providing the investigational drug, Silmitasertib (CX-4945). The clinical trial is conducted in two phases: the first phase focuses on establishing the safety and dosage of Silmitasertib (CX-4945) in pediatric patients with relapsed or refractory solid tumors, while the second phase evaluates its efficacy and potential as a novel treatment option. As high CK2 activity is noted across several pediatric cancers, including neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, osteosarcoma, medulloblastoma, and liposarcoma. Recent study has shown that CK2 is one of the key kinases that is essential for maintaining the stabilization of MYCN protein, the oncogenic driver in neuroblastoma. In view of the anti-tumor activity of CK2 inhibitor, the Beat Childhood Cancer Research Consortium at The Pennsylvania State University regards Silmitasertib (CX-4945) high therapeutic potential of treating pediatric cancers. Neuroblastoma is the most common type of solid malignant tumor in children, aside from brain tumors and lymphomas. Over 90% of cases are diagnosed before the age of 5. 70% of patients already have metastatic disease by the time symptoms appear, and the 20-year survival rate is only around 30%. In the US, there are 700-800 new cases each year, accounting for about 6% of childhood cancers, meeting the definition of a rare disease. Senhwa Biosciences is planning to apply for Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPD) for Silmitasertib (CX-4945) for the treatment of neuroblastoma. If these designations are granted and the drug is successfully commercialized, the company would obtain a Priority Review Voucher (PRV). The holder of a PRV can designate any future human drug application to receive priority review, potentially shortening the review time to 6 months, which could accelerate the timeline for the company (or its partners) to bring other products to market. The clinical trial design also includes Ewing's sarcoma and osteosarcoma, which are common pediatric bone cancers with poor prognoses, representing unmet medical needs. SOURCE Senhwa Biosciences, Inc.