PAD4

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

C4X Discovery Holdings Limited PatientSeek identifies a genetic signature that separates a4b7 integrin therapy responder and non-responder populations in inflammatory bowel disease Progresses precision method for patient selection - the right patient for the right medicine 16 September 2024 - C4X Discovery Holdings Limited (“C4XD”), the immuno-inflammation therapeutics company, today announces the discovery of a genetic response signature that identifies responder and non-responder groups amongst patients with ulcerative colitis, an inflammatory bowel disease (“IBD”), following treatment with the a4b7 integrin antibody vedolizumab. Clive Dix, Executive Chairman of C4XD, said: “Until now, no currently available biomarker has been robustly validated in predicting response to individual advanced therapies to guide clinical practice for IBD, leaving many patients underserved. Utilising our PatientSeek platform we have now identified a genetic response signature that separates responders and non-responders to vedolizumab, the a4b7 antibody therapy for ulcerative colitis. This is an incredibly exciting first for immuno-inflammation precision medicine as these data clearly demonstrate the power of PatientSeek’s analytical capabilities for patient selection based solely on genetic data. We will utilise the data’s predictive power for use in future clinical trials for our own small molecule a4b7 integrin programme and we will take this precision approach to progress our growing pipeline, including our TNFa and PAD4 programmes.” Precision medicine has the goal of identifying the right therapy that will be effective in the right patient at the right point in their disease progression. Championed originally in oncology, this approach is now gaining much attention from the scientific and medical community in the immuno-inflammation space. C4XD’s PatientSeek platform applies a unique mathematical approach to analyse datasets containing patients’ genetic records together with other information such as electronic health records. The resulting data can provide a statistically significant predictive ‘genetic response signature’. Genetic signatures, compared to clinical and omic biomarkers, have the significant advantage of not changing over time and are independent of disease progression. C4XD has accessed and analysed a large dataset which contains patients who have received vedolizumab and initial data have clearly demonstrated that, for the first time, responders and non-responders can be separated according to a genetic signature based on genetic variation in the non-coding regions of DNA. PatientSeek’s ability to identify genetic response signatures should lead to smaller, less expensive and more successful clinical trials targeting the right patient at the right time for the right drug. Contacts C4X Discovery HoldingsMo Noonan, Communications+44 (0)787 6444977 C4X Discovery Media – ICR ConsiliumMary-Jane Elliott, Chris Gardner, Angela Gray+44 (0)203 709 5700 Notes to Editors: About C4X DiscoveryC4X Discovery (C4XD) is a pioneering Drug Discovery company, combining scientific expertise with cutting-edge technologies to efficiently deliver world-leading medicines. We have a highly valuable and differentiated approach to Drug Discovery through our enhanced molecular design and patient stratification capabilities, generating small molecule drug candidates across multiple disease indications focused on immuno-inflammation. We are advancing our internal portfolio which ranges from early-stage target opportunities to late-stage Drug Discovery programmes and we have two commercially partnered programmes with Sanofi and AstraZeneca, and one clinical stage candidate which has been acquired by Indivior. For more information visit us at www.c4xdiscovery.com or follow us on twitter @C4XDiscovery.

C4X Discovery Holdings Limited C4XD announces progress on immuno-inflammation programmes and appointment of new Board members 22 July 2024 - C4X Discovery Limited (“C4XD”), a pioneering drug discovery company, today provides an update on the business following its delisting from AIM earlier in the year. Clive Dix, Executive Chairman of C4XD, said: “The great work at C4XD continues. We are utilising our strong capital position to drive forward our immuno-inflammatory portfolio, underpinned by our unique genetic insights platform. Our business development and scientific teams are hard at work presenting and networking at key scientific conferences and industry events, showcasing our expertise in immuno-inflammation, whilst ensuring that we have the right contacts in place for future collaborations. “With the shift in direction for the Company away from the public markets, we sadly say goodbye to Simon Harford, who has decided to step down after three years to focus on other commitments. Simon has provided invaluable support and guidance during his time with us, and we wish him the very best for his future projects. At the same time, we are delighted to welcome two new Non-Executive Board members: Harmesh Suniara, who joins us from Lombard Odier 1798 Volantis, a great supporter of our business; and Richard Jones, a respected finance operator within the industry. Each bring unique and important skills which will broaden and enhance the Board’s guidance and strategic direction to drive a successful future for the Company.” PipelineWe continue to advance our small molecule drug discovery portfolio against a range of targets in the immuno-inflammatory space where we have identified a combination of unmet medical need, significant commercial potential and practicable application of our core platforms, PatientSeek and Conformetrix. Our lead programme is an oral a4b7 integrin inhibitor for use in the treatment of inflammatory bowel disease (‘IBD’). This integrin is the target for the clinically successful biologic therapy Vedolizumab, (Entyvio), but a small-molecule alternative would broaden patient access. Our Discovery scientists are closing in on the shortlist of pre-clinical candidates with planning for IND-enabling studies well underway. In parallel, our Human Genetics team are applying our PatientSeek platform to analyse a number of databases in order to define a genetic fingerprint as a predictive genetic biomarker for a4b7 response that will allow us to specifically design our pivotal clinical trials for success. We have recently published our first disclosure on the PatientSeek platform as applied to Target Identification in rheumatoid arthritis (Scientific Reports, 14, 14153 (2024) doi.org/10.1038/s41598-024-64970-0). https://c4xdiscovery.com/unveiling-new-genetic-insights-in-rheumatoid-arthritis-for-drug-discovery-through-taxonomy3-analysis/ As part of C4XD’s journey from a Discovery to a Therapeutics company with a clinical pipeline, we are building our internal skillset appropriately whilst maintaining flexibility through a range of external consultants, CROs and CDMOs in our network. We are now disclosing two programmes in our pipeline behind our a4b7 programme in the Hit-To-Lead phase and progressing towards Lead Optimisation. The first is an oral PAD4 inhibitor for treatment of rheumatoid arthritis (RA). PAD4 is an enzyme involved in modifying a range of proteins through a process known as citrullination; citrullinated proteins have increased immunogenicity and arthritogenicity and their presence in arthritic joints correlates with disease severity. Attenuating this process therefore should provide an opportunity in moderate to severe rheumatoid arthritis with First-In-Class potential. Our second programme is an oral TNFa inhibitor targeting a Best-In-Class profile with multiple possible therapeutic applications, including RA and IBD. Tumor necrosis factor (TNF) is a cytokine with a major role in immune system homeostasis and is involved in a number of autoimmune and inflammatory diseases. Biologics have been developed to block TNF-dependant signalling cascades, but they are not without side-effects and have an effectiveness that often decreases over time. A small molecule therapy should be able to avoid such issues and provide an attractive alternative therapeutic option across a range of indications. We also have a number of programmes in early evaluation with the goal to assess their suitability for progression. BoardWe note the resignation of Simon Harford after three years on the Board and thank him for his support and counsel during this time. Separately, in line with the delisting Circular, we are delighted to welcome two new Non-Executive members to the C4XD Board appointed by Richard Griffiths and Lombard Odier Asset Management (Europe) Limited: Richard Jones is an experienced healthcare and life sciences Director. He was most recently CFO of Medica Group, a PE backed international tele-medicine business which was taken private in a £270m deal by IK partners from the UK main market; and is currently SID and Chair of the Audit Committee at Alliance Pharma PLC, an AIM listed consumer healthcare company. Richard previously gained extensive experience in the healthcare sector as CFO at UK AIM Listed companies Mereo BioPharma Group PLC and Shield Therapeutics PLC. At Mereo, he had a leading role in the merger with US listed OncoMed Pharmaceuticals, Inc and its subsequent dual listing on Nasdaq in 2019. At Shield, he established the finance operations and guided the company through several private financing rounds and its 2016 IPO. Prior to his CFO roles, Richard held senior investment banking positions at Investec and Brewin Dolphin Securities, where he advised healthcare clients on a wide range of transactions and fundraisings including IPOs, M&A and fundraisings. Richard qualified as a Chartered Accountant with PwC. Harmesh Suniara has over 15 years' experience of working in investment management, with a particular focus on UK small and mid-cap equities including the technology and life sciences sectors. He brings a wealth of expertise in active engagement with companies that Lombard Odier has invested in. He has worked as a Portfolio Manager at Lombard Odier 1798 Volantis since 2017, and prior to this he was an Investment Manager at Henderson Volantis Capital and Gartmore Investment Management. Harmesh graduated in Physics from the University of Cambridge. Lombard Odier 1798 Volantis is a major shareholder in C4X Discovery. Contacts C4X Discovery HoldingsMo Noonan, Communications+44 (0)787 6444977 C4X Discovery Media – ICR ConsiliumMary-Jane Elliott, Chris Gardner, Angela Gray+44 (0)203 709 5700 Notes to Editors: About C4X DiscoveryC4X Discovery (C4XD) is a pioneering Drug Discovery company, combining scientific expertise with cutting-edge technologies to efficiently deliver world-leading medicines. We have a highly valuable and differentiated approach to Drug Discovery through our enhanced molecular design and patient stratification capabilities, generating small molecule drug candidates across multiple disease indications focused on immuno-inflammation. We are advancing our internal portfolio which ranges from early-stage target opportunities to late-stage Drug Discovery programmes and we have two commercially partnered programmes with Sanofi and AstraZeneca, and one clinical stage candidate which has been acquired by Indivior. For more information visit us at www.c4xdiscovery.com or follow us on twitter @C4XDiscovery.