MTAP

JBI-802 is a first-in-class, orally administered, inhibitor of CoREST complex JBI-778 is a potential best-in-class, orally administered, brain penetrant inhibitor of PRMT5 MORRISVILLE, N.C., Oct. 25, 2024 /PRNewswire/ -- Jubilant Therapeutics Inc., a biopharmaceutical company advancing small molecule precision therapeutics to address unmet medical needs in oncology and autoimmune diseases, today announced the dosing of first patients in global clinical trials involving two pipeline programs: Phase I/II clinical trial of JBI-802 in heme-oncology and Phase I clinical trial for JBI-778 in solid tumors. "We are excited to take this significant step forward in our mission to transform the lives of patients through the development of easy to administer precision oral medicines with enhanced safety and therapeutic efficacy," said Hari S Bhartia, Chairman, Jubilant Therapeutics Inc. JBI-802 is a first-in-class, orally administered, small-molecule dual inhibitor of LSD1 (Lysine-specific histone demethylase 1A) and HDAC6 (Histone deacetylase 6) within the CoREST (Co-repressor of Repressor Element-1 Silencing Transcription) complex. In the earlier Phase I study conducted in advanced solid tumor patients, JBI-802 showed a dose-proportional increase in exposure across cohorts and a strong correlation between exposure and the on-target effect of platelet decrease. There were no reports of Dysgeusia and Anemia, typical adverse events seen with LSD1only inhibitors. The Phase I trial also showed anti-tumor activity in Non-Small Cell Lung Cancer (NSCLC) patients including a confirmed partial response. Overall, the study results provided human proof-of-principle for expanding the development of JBI-802 in Essential Thrombocythemia and Myelodysplastic Syndrome/Myeloproliferative Neoplasms (MDS/MPN) with thrombocytosis. Essential Thrombocythemia is a chronic disease of excessive platelets with over 100,000 patients in the United States for whom the primary treatment is hydroxyurea, a therapy that poses severe limitations for patients in terms of both safety and efficacy. The second clinical trial is to assess both safety and the recommended Phase II dose for JBI-778, an oral brain-penetrant inhibitor of PRMT5 (Protein arginine N-methyltransferase 5) in mEGFR Tyrosine Kinase Inhibitor (TKI) resistant NSCLC, IDH+ high-grade glioma (HGG) and Adenoid Cystic Carcinoma (ACC). PRMT5, although a proven pathway for multiple cancers, has produced mixed results in terms of drug development due to safety concerns surrounding SAM competitive approach to PRMT5 inhibition and patient segment limitations of MTAP null tumor-focused approach PRMT5 inhibition. JBI-778 is a unique substrate competitive brain penetrant PRMT5 inhibitor that has shown no adverse effects in preclinical setting and can address both MTAP null and wild type tumors as well as brain tumors, catering to a larger patient segment including those with brain metastases. "The two most advanced novel drug candidates at Jubilant Therapeutics Inc. were discovered in-house using our TIBEO (Therapeutic Index and Brain Exposure Optimization) Discovery Engine. It is our unique approach of structure-based drug design to generate novel pharmacophores with improved therapeutic index compared to existing agents. We are excited to advance both JBI-802 and JBI-778 in genetically-defined subsets of patients with select hematological and solid tumor indications with high unmet medical needs. Initial clinical data are expected to read out in 2025," said Syed Kazmi, Chief Executive officer, Jubilant Therapeutics Inc. About JBI-802 JBI-802 is novel, oral, potent and selective dual inhibitor of two epigenetic targets of the CoREST complex: LSD1 and HDAC6. It targets stem cell modulation by inhibiting LSD1 and modulates immune suppression with isoform selective HDAC6 inhibition. Preclinical research has demonstrated its synergistic anti-tumor activity, which is superior compared to either target alone and with a favorable safety profile. JBI-802 is under evaluation in both hematological cancers such as acute myeloid leukemia, myelodysplastic syndrome and other myeloproliferative cancers as well as solid tumors, such as non-small cell lung cancer and small cell lung cancer. About JBI-778 JBI-778 is novel, oral, potent and brain penetrant inhibitor of PRMT5. JBI-778 targets the substrate site and stabilizes SAM bound to PRMT5, providing high biological selectivity and has shown a superior safety profile as seen in animals. Preclinical research has demonstrated significant activity in Tyrokinase-Inhibitor resistant cell lines, brain tumor and NSCLC. JBI-778 is under evaluation in solid tumors such as NSCLC, High Grade Glioma and Adenoid Cystic Carcinoma. About Jubilant Therapeutics Inc. Jubilant Therapeutics Inc. is a clinical stage biopharmaceutical company developing precision oral medicines with enhanced therapeutic index to address unmet medical needs in oncology and autoimmune diseases for genetically defined patients. Its advanced structure-based discovery engine, TIBEO (Therapeutic Index and Brain Exposure Optimization), has been validated through successful partnerships. The Company's clinical pipeline consists of a first-in-class dual CoREST modifier, JBI-802, currently in a Phase I/II clinical trial in multiple tumors and a novel brain-penetrant modulator of PRMT5, currently in Phase I clinical trial. Additional pre-clinical programs include brain penetrant and gut restrictive PDL1 inhibitors, as well as PAD4 inhibitors for oncology and inflammatory indications. The Company is headquartered in Pennsylvania and guided by globally renowned scientific advisors. For more information, please visit or follow us on Twitter @JubilantTx and LinkedIn. Logo: SOURCE Jubilant Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Bristol Myers Squibb and Ideaya Biosciences both released detailed snapshots of early-stage data for cancer drugs targeting solid tumors with a certain mutation known as MTAP deletion. There are no approved therapies specifically for MTAP deletions, though these tumors can be found in a wide range of cancer types, such as urothelial, lung, pancreatic and others. Either drug would allow patients an additional option if they end up resistant to other therapies like checkpoint inhibitors. While the companies are separately working to treat the same kinds of cancer mutations, their drugs act differently. Bristol Myers’ program, called BMS-986504, is a next-generation PRMT5 inhibitor that affects the binding of PRMT5 and MTA (the “PRMT5-MTA complex”) in an attempt to avoid off-target toxicity from earlier-in-class drugs. Ideaya’s therapy, codenamed IDE397, is a MAT2A inhibitor and is designed on the concept of synthetic lethality, where tumors with certain genetic aberrations become dependent on another cellular pathway. By blocking MAT2A, IDE397 can effectively treat patients with MTAP-deletion solid tumors, Ideaya says. Bristol Myers said Friday that, as of May 15, it enrolled 125 patients, 107 of whom were evaluable for efficacy. Of those patients, 21 achieved a partial response, good for an ORR of 20%. There were no complete responses, and the median duration of response was 4.8 months, with a median follow-up of 5.8 months. BMS measured seven different dose levels, but did not break down efficacy by each specific dose. The highest ORR came in mesothelioma, with three of seven patients achieving a partial response for 43%. Median duration of response was not reached. In NSCLC, six of 20 patients reached a partial response (30% ORR) with a median duration of response of 6.8 months. Pancreatic ductal adenocarcinoma had the lowest response rate, with three of 30 patients achieving partial response (10%). Treatment-related side effects were observed in 74% of the 125-patient sample, including 12% who saw grade 3 or higher adverse events. The most common side effects were nausea, vomiting, fatigue, diarrhea and decreased appetite. Additionally, 2% of patients discontinued treatment due to side effects. Ideaya’s data build on a July readout from an 18-patient sample. In the new dataset, there are 27 patients evaluable for efficacy as of an Aug. 22 cutoff. Nine of the 27 patients responded to the therapy, including one complete response and eight partial responses (33% ORR, down from 39% in July). Enrolled patients had either urothelial cancer, squamous NSCLC or adenocarcinoma NSCLC with MTAP deletions. The median duration of response is still immature, Ideaya said, as is median progression-free survival. The median duration of treatment has also not been reached. Treatment-related side effects were observed in 54% of patients, including 18% who saw grade 3 or higher adverse events (though none of those observed in more than 5% of patients). The most common side effects were peripheral neuropathy (none at grade 3 or higher), decreased appetite, blood creatinine increase, nausea, fatigue and asthenia. In addition to the monotherapy, Ideaya is also testing IDE397 with BMS-986504 and an experimental PRMT5 inhibitor from Amgen.

~33% ORR by RECIST 1.1: 1 CR + 8 PRs out of 27 evaluable heavily pre-treated (median 2-3 prior lines, ranging from 1-7) MTAP-deletion UC and NSCLC patients 9 of 9 responses have confirmed by RECIST 1.1 (5 confirmed responses out of 18 evaluable patients reported on July 8, 2024, IDE397 webcast) MTAP-deletion UC: 40% (4 of 10) confirmed ORR and 3 pts on treatment >250 days MTAP-deletion SqNSCLC: ~38% (3 of 8) confirmed ORR and 4 pts on treatment >200 days Multiple PRs with genetic co-alterations, including MTAP-deletion and KRAS G12D mutation in NSCLC, and MTAP-deletion and FGFR-TACC3 fusion in UC Median DOT not yet reached and >6.2 months, and median TTR ~2.7 months ~81% (17 of 21) ctDNA MRR, and high DCR of 93% (25 of 27 with SD or better) AE Profile: No drug-related SAEs or discontinuations at 30 mg once-a-day expansion dose Targeting expansion of Phase 1/2 study of IDE397 in combination with Trodelvy® in MTAP-deletion UC in Q4 2024; patient case study of PR by RECIST 1.1 and rapid >95% ctDNA reduction of combination will be presented at ENA 2024 IDE397 demonstrated deep and durable regressions in combination with PRMT5 inhibitors BMS-986504 and AMG 193 in preclinical models SOUTH SAN FRANCISCO, Calif., Oct. 25, 2024 /PRNewswire/ -- IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, announces Phase 1 expansion data for IDE397 in methylthioadenosine phosphorylase (MTAP)-deletion urothelial cancer (UC) and non-small cell lung cancer (NSCLC) patients as a late breaker abstract (LBA) oral presentation at the 36th edition of the EORTC-NCI-AACR Symposium (ENA 2024) in Barcelona, Spain. In addition, IDEAYA had additional poster presentations at ENA 2024 highlighting preclinical data for the MAT2A and PARG programs. IDE397 is a potent and selective potential first-in-class methionine adenosyltransferase 2 alpha (MAT2A) inhibitor in Phase 2 clinical trials for the treatment of MTAP-deletion solid tumors. "We are excited by the clinical efficacy and safety profile observed with the potential first-in-class MAT2A inhibitor IDE397 at the 30mg once-a-day RP2D, including multiple confirmed responses observed as a monotherapy agent in non-small cell lung cancer and urothelial cancer patients with MTAP-deletion. In addition, at the 30mg once-a-day expansion dose, we observed a manageable safety profile with no drug-related serious adverse events or discontinuations. These data support potential combination development," said Dr. Benjamin Herzberg, M.D., Assistant Professor of Medicine, Columbia University. "The clinical data update from the late breaker oral presentation at ENA 2024 provides further clinical proof-of-concept for IDE397 in the setting of MTAP-deletion urothelial cancer and non-small cell lung cancer to deliver a high disease control rate and confirmed RECIST responses, with an overall manageable adverse event profile," said Darrin M. Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences. "IDE397 is rapidly advancing as a monotherapy agent in MTAP-deletion urothelial cancer and non-small cell lung cancer. Next, we are well positioned to advance our broad and potential first-in-class IDE397 rational combination strategy, including the targeted expansion in the fourth quarter with Trodelvy® in urothelial cancer, the ongoing combination with AMG 193 with targeted expansion in NSCLC, combinations with IDEAYA's internal MTAP-deletion pipeline that includes a targeted development candidate by year-end, among others," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences. There are currently no FDA-approved therapies for patients with MTAP-deletion solid tumors, highlighting the unmet medical need. The priority MTAP-deletion solid tumor types for the IDE397 Phase 1/2 monotherapy program are UC and NSCLC. MTAP-deletion has been reported at over 15% in NSCLC and over 25% in UC, based on The Cancer Genome Atlas (TCGA) database. We estimate that the annual incidence of MTAP-deletion in the U.S. in UC and NSCLC is approximately 48,000 patients, based on the 2024 Surveillance, Epidemiology, and End Results (SEER) database. In addition, there are several potential expansion MTAP-deletion solid tumor types that are also being considered for monotherapy and combination development, including pancreatic, gastric, esophageal, and head and neck cancer, among others. Based on the TCGA database, MTAP-deletion in pancreatic cancer has been reported in more than 20% of patients, representing a U.S. annual incidence of approximately 14,000 patients. ENA 2024 Clinical Data Update – IDE397 Phase 2 Expansion in Subjects with MTAP-Deletion UC and NSCLC The company observed encouraging clinical activity at the 30 mg once-a-day (QD) Recommended Phase 2 Dose (RP2D) in its Phase 1 clinical trial evaluating its potential first-in-class MAT2A inhibitor IDE397 in heavily pre-treated MTAP-deletion UC and NSCLC patients. The patients evaluated had a median of two (2) to three (3) prior lines-of-therapy, ranging from one (1) to seven (7). The reported Phase 1 clinical expansion data are based on twenty-seven (27) evaluable MTAP-deletion patients, including ten (10) UC, nine (9) adenocarcinoma NSCLC, and eight (8) squamous (sq) NSCLC patients at the expansion dose of 30 mg QD of IDE397. The clinical efficacy and tolerability data are preliminary and based on investigator review from an unlocked database as of the data analysis cutoff date of August 22, 2024. The clinical data update in the twenty-seven (27) evaluable patients by RECIST 1.1 include: ~33% Overall Response Rate (ORR). One (1) complete response (CR) and eight (8) partial responses (PRs) by RECIST 1.1 evaluation out of twenty-seven (27) evaluable patients. Nine (9) of nine (9) responses have been confirmed by RECIST 1.1, including four (4) UC patients, of which one was a CR, three (3) squamous NSCLC patients, and two (2) adenocarcinoma NSCLC patients. Two patients confirmed after the data cutoff date. In the earlier reported July 8, 2024, IDE397 webcast program update, five (5) confirmed responses were reported out of eighteen (18) evaluable patients. There were zero (0) non-evaluable patients reported as of the data analysis. Confirmed ORR% by RECIST 1.1 by Solid Tumor Type: MTAP-deletion UC = 40% (4 of 10) confirmed ORR%; MTAP-deletion squamous NSCLC = ~38% (3 of 8) confirmed ORR%; MTAP-deletion adenocarcinoma NSCLC = ~22% (2 of 9) confirmed ORR% Multiple confirmed partial responses by RECIST 1.1 harbor genetic co-alterations, including MTAP-deletion and KRAS G12D mutation in NSCLC, and MTAP-deletion and FGFR-TACC3 fusion in UC ~93% Disease Control Rate (DCR). One (1) CR, eight (8) PRs, and sixteen (16) stable disease (SD) by RECIST 1.1 evaluation out of twenty-seven (27) evaluable patients Preliminary durability assessment: Fifteen (15) of twenty-seven (27) patients still on treatment. Seven (7) of nine (9) RECIST 1.1 responses remain on treatment. Median duration of treatment (DOT) has not been reached and is greater than 6.2 months and median time to response (TTR) is ~2.7 months. The median duration of response and median progression free survival data is still immature. Three (3) UC patients on treatment greater than 250 days, four (4) squamous NSCLC patients on treatment greater than 200 days, and three (3) adenocarcinoma NSCLC patients on treatment greater than 200 days ~81% ctDNA Molecular Response Rate (MRR). Seventeen (17) of twenty (21) patients with 50% or greater ctDNA reduction, and ~33% (7 of 21) with deep 90% or greater ctDNA reduction. All MRs (17 of 17) were rapid occurring at the first ctDNA sample analysis. There were several quality control failures of patient samples that led to unavailability for MR analysis Favorable adverse event (AE) profile. Approximately 18% grade 3 or higher drug-related AEs and no drug-related serious adverse events (SAEs) observed at the IDE397 30mg once-a-day expansion dose. No drug-related AEs leading to discontinuations were observed. We anticipate that the favorable AE profile and dosing convenience of a 30 mg once-a-day tablet has the potential to enable long-term dosing and combination development, including with MTA-cooperative PRMT5 inhibitors and topoisomerase payload antibody drug conjugates (ADCs) ENA 2024 IDE397 and Trodelvy Clinical Combination Case Study in MTAP-deletion UC IDEAYA reports the first preliminary clinical case study of the IDE397 and Trodelvy combination in MTAP-deletion UC, including a PR by RECIST 1.1 in a patient case report with a genetic co-alteration of MTAP-deletion and a FGFR3-TACC3 fusion, and rapid and deep first-evaluation molecular responses with ctDNA reduction of greater than 95% observed that will be presented at ENA 2024. IDEAYA is targeting to initiate the IDE397 and Trodelvy Phase 1/2 combination expansion in MTAP-deletion UC in Q4 2024. IDEAYA has activated over 35 clinical trial sites globally in the U.S., Canada, Europe, and Asia Pacific to enable potential rapid enrollment for the IDE397 Phase 2 monotherapy expansion in MTAP-deletion lung and bladder cancer in its ongoing trial (NCT04794699). There is also an ongoing Amgen-sponsored Phase 1/2 trial of the IDE397 and AMG 193 combination in MTAP-Deletion NSCLC (NCT05975073). IDEAYA published at ENA 2024 preclinical combination efficacy data and the combination mechanistic rationale for IDE397 with clinical stage PRMT5 inhibitors, including BMS-986504 and AMG 193. Next, IDEAYA is enrolling a Phase 1 clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of IDE397 in combination with Trodelvy in MTAP-deletion UC patients (NCT04794699). Pursuant to the clinical study collaboration and supply agreement, IDEAYA and Gilead retain the commercial rights to their respective compounds, including with respect to use as a monotherapy or combination agent. IDEAYA is the study sponsor and Gilead will provide the supply of Trodelvy to IDEAYA. IDE397 monotherapy or in combination with Trodelvy has not been approved by any regulatory agency and the efficacy and safety of this combination has not been established. 36th edition of the EORTC-NCI-AACR Symposium (ENA 2024) in Barcelona, Spain Details of the late breaker oral presentation today are as follows: Presenter: Dr. Benjamin Herzberg, MD, Assistant Professor, Columbia University Title: Phase 1 expansion results of IDE397, a first-in-class, oral, MAT2A inhibitor (MAT2Ai) in MTAP deleted(del) non-small cell lung cancer (NSCLC) and urothelial cancer (UC) Abstract #: 501 LBA Session: Plenary Session 7, Late Breaking Abstracts and Proffered Papers: Novel discoveries in drug development Date and Time: Friday, October 25, 2024 at 3:54pm CEST In addition, IDEAYA had additional poster presentations at ENA 2024 highlighting preclinical data for the MAT2A and PARG programs. In the ENA 2024 concomitant publication, IDE397 demonstrated deep and durable regressions in combination with clinical stage PRMT5 inhibitors BMS-986504 and AMG 193 in multiple MTAP-deletion preclinical models. Poster presentation details are below: Author: Garbett, D. et al. Title: The mechanistic basis of both deep and durable antitumor activity by combinatorial inhibition of MAT2A and PRMT5 in MTAP-deleted tumors Poster Number: PB204 Session Title: Combination Therapies Date and Time: Thursday, October 24, 2024, 9:00am - 5:30pm CEST, Exhibition Hall Author: Munoz, D. et al. Title: IDE161, a potential first-in-class clinical candidate PARG inhibitor, selectively targets solid tumors with replication stress and DNA repair vulnerabilities Poster Number: PB337 Session Title: DNA Repair Modulation (e.g. PARP, CHK, ATR, ATM) Date and Time: Friday, October 25, 2024, 9:00am - 3:00pm CEST, Exhibition Hall The IDE397 late breaker oral presentation at ENA 2024, as well as an updated corporate presentation, which will incorporate the IDE397 Phase 1 clinical data update from ENA 2024 at the 30mg RP2D in UC and NSCLC patients, will be available on the company's website, at its Investor Relations portal at approximately 10:15 am ET on Friday, October 25, 2024, after the presentation has concluded. About IDEAYA Biosciences IDEAYA is a precision medicine oncology company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics. IDEAYA's approach integrates capabilities in identifying and validating translational biomarkers with drug discovery to select patient populations most likely to benefit from its targeted therapies. IDEAYA is applying its research and drug discovery capabilities to synthetic lethality – which represents an emerging class of precision medicine targets. Forward-Looking Statements This press release contains forward-looking statements, including, but not limited to, statements related to (i) expectations regarding the clinical activity profile and potential advantages of IDEAYA's clinical programs, (ii) the timing of enrollment for the IDE397 Phase 2 monotherapy expansion in MTAP-deletion lung and bladder cancer, (iii) the timing of initiation of the IDE397 and Trodelvy Phase 1/2 combination expansion in MTAP-deletion UC and (iv) the timing and content of future presentations. Such forward-looking statements involve substantial risks and uncertainties that could cause IDEAYA's preclinical and clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including IDEAYA's programs' early stage of development, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, IDEAYA's ability to successfully establish, protect and defend its intellectual property, and other matters that could affect the sufficiency of existing cash to fund operations. IDEAYA undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of IDEAYA in general, see IDEAYA's Annual Report on Form 10-K dated February 20, 2024 and any current and periodic reports filed with the U.S. Securities and Exchange Commission. Investor and Media Contact IDEAYA Biosciences Andres Ruiz Briseno SVP, Head of Finance and Investor Relations [email protected] SOURCE IDEAYA Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED