FOXP3

LPX-TI641 is an oral novel Treg-expanding T cell/transmembrane, immunoglobulin, and mucin (Tim)receptor agonist therapy in development for the treatment of autoimmune diseases such as rheumatoid arthritis, psoriatic arthritis, and multiple sclerosis with the intent to expand into additional therapeutic indications. In healthy adults, LPX-TI641 was orally bioavailable and was safe and well tolerated up to the highest tested doses. Exploratory pharmacodynamic endpoints showed an exposure-dependent, statistically significant increase in both regulatory T and B cells (T-regs and B-regs) compared to pooled placebo group. LAPIX cleared a second Investigational New Drug (IND) for LPX-TI641 with the rheumatology division at the US-FDA. LAPIX will initiate a Phase 1b study for Rheumatoid arthritis (RA) in Q4 2024. Nov. 20, 2024 -- LAPIX Therapeutics, Inc. (“LAPIX”), a clinical-stage biopharmaceutical company focused on developing novel, orally bioavailable immune system restoration therapies for autoimmune diseases based on agonism of TIM (T cell/transmembrane, immunoglobulin, and mucin receptor), today announced positive topline results from its Phase I randomized, double-blind, placebo-controlled single and multiple-ascending dose (SAD and MAD) trial to assess the safety, tolerability, and pharmacokinetics (PK) of LPX-TI641 after oral dosing in healthy adult volunteers, LPX641-101 (NCT05853835). The Phase 1 clinical trial results showed LPX-TI641 to be safe and well tolerated over the course of the tested oral doses from 10 mg to 150 mg in the SAD, and 30 mg to 120 mg once daily oral doses for up to 7 days in the MAD portion of the trial. A maximum tolerated dose was not identified in this trial. Adverse events were primarily mild and were sporadically observed across both placebo and treatment groups and not linked to dosage levels. Mild headaches were the most reported adverse event. Notably, treatment-emergent neutropenia and lymphocytopenia - two of the most common side effects associated with autoimmune therapies - were absent in subjects administered various doses of LPX-TI641. "We are committed to innovating around the complexities of the immune system,” said Anas M. Fathallah, Ph.D., co-founder and CEO of LAPIX. “The emerging preliminary data, particularly the observed exposure dependent changes in our key exploratory biomarkers, T-regs and B-regs, highlight LPX-TI641’s potential as a leading therapy for autoimmune disease. We are eager to advance this promising candidate into a Phase Ib study in RA and PsA and create a potential new oral standard of care for patients battling autoimmune diseases.” LPX-TI641 demonstrated oral bioavailability with a dose-dependent increase in exposure at higher doses. Preliminary exploratory pharmacodynamic data from the study revealed an LPX-TI641 exposure dependent and statistically significant increase in circulating CD4+/Foxp3+ T-cells (T-regs) and CD25+/CD19+ B-cells (B-regs) compared to pooled placebo group. The Phase I clinical trial utilized six SAD and three MAD cohorts. A total of 72 subjects (eight subjects per cohort, six on active treatment and two on placebo) were enrolled consecutively in the study. Out of the 72 subjects, 70 completed all scheduled study activities and visits. Two subjects withdrew from the study for personal reasons conflicting with study activities, unrelated to drug adverse effects. LPX-TI641 is an oral, small-molecule designed to bind the phosphatidylserine binding pocket on the T cell/transmembrane, immunoglobulin, and mucin (Tim) family of receptors. It is currently under clinical development for autoimmune indications such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and multiple sclerosis with plans to expand to other autoimmune indications where the underlying pathology involves immune imbalances and loss of self-tolerance. LPX-TI641’s primary pharmacology works to restore the adaptive immune system’s self-tolerance rather than suppressing immunity, enabling patients to more effectively and gently combat autoimmune disease. Toxicological studies and emerging clinical data show that LPX-TI641 does not induce neutropenia or lymphocytopenia, suggesting a potentially improved safety profile compared to current therapies. LAPIX Therapeutics is a Cambridge, MA-based clinical-stage biopharmaceutical company focused on developing novel, first in class, oral immune system restoration therapeutics for the treatment of autoimmune diseases. Our scientific approach to developing Tim agonists (T-cell immunoglobulin and mucin domain) and restoring the natural immune tolerance pathway with potent small molecules reflects our passion for progressive and patient-centric approaches. For more information, please visit: www.LAPIX.com. The content above comes from the network. if any infringement, please contact us to modify.

Achievement of first significant research milestone triggers an option exercise payment of $10 million from AstraZenecaAstraZeneca will progress preclinical and clinical development of the selected lead T1D candidateQuell will be accountable for CMC in support of CTA/IND-enabling studies and GMP product supply for a first-in-human trial London, UK – November 18, 2024 – Quell Therapeutics Ltd (“Quell”), a leader in developing engineered T-regulatory (Treg) cell therapies for serious medical conditions driven by the immune system, announces that AstraZeneca has selected a candidate to progress in the Type 1 Diabetes (T1D) Treg cell therapy program. This is the first significant research milestone achieved under its 2023 collaboration agreement with AstraZeneca to develop, manufacture and commercialize autologous, engineered Treg cell therapies for two autoimmune disease indications – T1D and Inflammatory Bowel Disease (IBD). As a result of this research milestone, AstraZeneca has exercised its exclusive option to license the potential therapy for further development and commercialization, resulting in a milestone payment to Quell of $10 million. AstraZeneca will now progress further CTA/IND-enabling studies and clinical development of the selected candidate, with Quell providing chemistry, manufacturing and controls (CMC) support including GMP supply of drug product for a first-in-human trial. Quell retains an option to co-develop the optioned T1D candidate in the United States in exchange for additional milestone payments and increased royalties on US net sales. Iain McGill, CEO of Quell Therapeutics, said: “Our collaboration with AstraZeneca is progressing extremely well and the achievement of this first significant milestone in the Type 1 Diabetes program is highly encouraging. It highlights the strong commitment and rapid integration of our respective research teams as well as providing important early validation of our novel CAR-Treg cell therapy approach to autoimmune diseases. Further, the nomination of this first candidate in T1D nicely complements the advances we are making with QEL-001, our internal program in transplantation, and demonstrates the potential of our powerful technology to unlock a broad opportunity across autoimmune and inflammatory diseases.” Regina Fritsche Danielson, SVP and Head of Early Research & Development, Cardiovascular, Renal and Metabolism at AstraZeneca, added: “We are pleased to have achieved this important early milestone in our collaboration with Quell Therapeutics. Type 1 Diabetes can be challenging for patients in terms of long-term disease management and impact on quality of life, with no options for disease-modifying therapies. Our ambition with this CAR-Treg program is to harness the body’s immune system to target disease drivers in T1D and potentially slow or stop disease progression.” ### Notes to Editors About the Agreement with AstraZeneca Quell and AstraZeneca entered a collaboration, exclusive option and license agreement in June 2023 to develop, manufacture and commercialize autologous, engineered Treg cell therapies for two autoimmune disease indications – Type 1 Diabetes (T1D) and Inflammatory Bowel Disease (IBD). The agreement centres on the application of Quell’s proprietary toolbox of Treg cell engineering modules, including its Foxp3 Phenotype Lock, to develop multi-modular autologous Treg cell therapy candidates in both disease areas. Quell received $85 million in upfront payments from AstraZeneca and is eligible to receive over $2 billion for further development and commercialization milestones, if successful, plus tiered royalties. In addition, Quell retains an option to co-develop Treg cell therapies from the T1D program with AstraZeneca in the United States in exchange for additional milestone payments and increased royalties on US net sales. About Quell Therapeutics Quell Therapeutics is the world leader in developing engineered T-regulatory (Treg) cell therapies that aims to harness, direct and optimize their immune suppressive properties to address serious medical conditions driven by the immune system. The Company is leveraging its pioneering Foxp3 Phenotype Lock™ technology, unique multi-modular platform and integrated manufacturing capabilities to design and develop a pipeline of highly engineered Treg cell therapies with greater potential for persistence, potency and stability than earlier generations of Treg cell therapy approaches. Quell’s lead candidate QEL-001 is advancing in the Phase 1/2 LIBERATE clinical trial designed to investigate its ability to induce operational tolerance following liver transplantation, with the potential to protect the post-transplant liver without the need for chronic immunosuppressive medications. Quell is also advancing additional programs in Type 1 Diabetes and Inflammatory Bowel Disease with AstraZeneca, iPSC-derived allogeneic Tregs and multiple discovery research programs. www.quell-tx.com. Contacts Luke Henry, Chief Business Officer Quell Therapeutics IR@quell-tx.com Media: Mark Swallow, Sandi Greenwood, Erica Hollingsworth MEDiSTRAVA Quell-Tx@Medistrava.com Investors: Corey Davis LifeSci Advisors cdavis@lifesciadvisors.com

Quell’s Treg platform induces sustained expression of FOXP3. Image credit: Shutterstock/ Vink Fan. AstraZeneca has exercised an option to license a cell therapy from Quell Therapeutics, resulting in a $10m milestone payment heading to the latter company. AstraZeneca has selected a candidate to progress in the type 1 diabetes (T1D) Treg cell therapy programme, as per an 18 November press release. It is the first asset licensed by the British big pharma as part of an ongoing collaboration with London-based biotech Quell since last year. AstraZeneca will now take on future duties of the therapy, including clinical trial application and investigational new drug application-enabling studies. Quell will continue to provide chemistry, manufacturing and controls (CMC) support, including supplying the drug product for a first-in-human trial. According to the deal, the biotech has the option to continue working alongside AstraZeneca and the selected T1D candidate in the US, gaining co-development rights in exchange for additional milestone payments and increased royalties on net sales in the country. AstraZeneca and Quell signed their collaboration deal last year targeting two autoimmune diseases, T1D and inflammatory bowel disease (IBD). The deal included an $85m upfront payment, along with more than $2bn in milestone payments. At the time, AstraZeneca’s BioPharmaceuticals R&D executive vice-president Mene Pangalos said the company was excited to explore the “untapped potential with Treg cell therapies in autoimmune indications”. Treg therapy, so-called because it harnesses regulatory T cells, is an emerging treatment for several diseases that occur due to an overactive immune system, such as autoimmune disorders. AstraZeneca hasn’t been the only big pharma company to be attracted by the technology – Bristol Myers Squibb (BMS) made an equity investment in Abata Therapeutics in August to advance a multiple sclerosis candidate. Founded in 2019 with six Treg specialists from University College London and King’s College London, Quell has developed a platform that works by ensuring the sustained expression of forkhead box P3 (FOXP3) in Treg cells. This protein is a crucial regulator of Treg cell gene expression and is thus involved in much of their suppressive activity. Quell’s pipeline is headed by QEL-001, a Treg therapy to help acceptance in liver transplantations, currently in a Phase II trial (NCT05234190). Three other programmes are at the preclinical stage, including QEL-003 for IBD in collaboration with AstraZeneca. The licence option comes at a time of uncertainty for AstraZeneca, whose shares dropped last week following US President-elect Donald Trump’s decision to appoint vaccine sceptic Robert F Kennedy Jr as head of the Department of Health and Human Services (HHS). AstraZeneca, which made a name for itself in the Covid-19 pandemic with its vaccine co-developed with the University of Oxford, is currently embarking on a major US expansion , including a bolster to manufacturing capacity in the country. Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Cell and gene therapies: Pipe dream to pipeline The cell and gene industry is gaining momentum, with a new wave of therapies promising to transform the way doctors treat, and even cure, disease. In this report, Cytiva and GlobalData have collaborated to explore the rise of the cell and gene therapy industries, the current state of the market, present and future opportunities for advancement, and the challenges that lie ahead. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic By downloading this Whitepaper, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy