Sareum Holdings plc (SAR) Earnings Call Transcript & Summary

Hello. My name is Tim Mitchell, and I'm CEO and a founder of Sareum. Thank you for watching Sareum's LSX Presentation that will showcase our next-generation TYK2 JAK1 immunotherapeutics and their potential to treat autoimmune diseases, cancer and, in particular, current interest, the cytokine storm that is often the case of death in COVID-19 patients. Sareum is a name listed company. So first, I need to show this disclaimer. Our business model is to take small molecule inhibitors into early clinical development and then license them on. This model has been validated by CHK 1 kinase cancer program. Working with CI UK-funded organizations, we developed SRA737 and took it into Phase I studies before it was licensed to Sierra Oncology in a $300 million deal. Internally, we're focusing on our TYK2/JAK1 kinase inhibitor programs: SDC-1801, targeting autoimmune diseases; and SDC-1802, targeting cancer and cancer immunotherapy. TYK2 and JAK1 are members of the JAK family of self-signaling enzymes, which are important for maintaining a healthy, well-balanced immune system and, as such, are targets of great interest for the pharmaceutical industry. There's been good clinical validation for TYK2 and TYK2/JAK1 inhibitors from BMS and Pfizer in psoriasis and psoriatic arthritis, but we believe there's room for improvement. These companies are running further Phase II studies in several other autoimmune diseases, including lupus, ulcerative colitis and Crohn's disease with readouts expected this year and next. JAK family kinases transmit extracellular signals from cytokine receptors through to the stack transcription factors. First-generation JAK inhibitors such as baricitinib and tofacitinib target JAK2 and JAK3 as well as JAK1. And it is this JAK2 and JAK3 inhibition that's believed to be responsible for the FDA black box warning for serious infections, lymphoma and thrombosis that have been issued to these first-gen JAK inhibitors. Sareum's next-generation JAK inhibitors target TYK2 and JAK1, which signal all the therapeutic and relevant cytokines shown here and are associated with autoimmune diseases such as psoriasis, arthritis, IBD and lupus. Our inhibitors are very selective against JAK2 and JAK3, so we'd not expect to see the serious side effects that can arise from JAK2 and JAK3 inhibition. So we believe there are clear opportunities here for Sareum. There are no TYK2 selective products on the market, and there are no TYK2 inhibitors in clinical trials for cancer, giving us a first-in-class opportunity. Sareum is developing 2 distinct TYK2/JAK1 kinase inhibitors. Both are potent inhibitors of TYK2 and JAK1 and are selected over JAK2 and JAK3 and the rest of the kinome. We're dosing orally twice daily in mouse models, what we believe we'll be able to dose once-daily in any human studies. We're aiming to complete IND-enabling studies on SDC-1801 in the next few months and file for clinical trial approval shortly after. There are some data on SDC-1801, our preclinical candidate for autoimmune diseases. We've got dose-dependent efficacy in rheumatoid arthritis models. And we see similar efficacy in psoriasis, ulcerative colitis and lupus models with this and closely related compounds. In preclinical safety studies, we're dosing at over 30x the therapeutic levels before seeing any dose-limiting tops. The synthetic group for SDC-1801 has been developed, and we're able to manufacture hundreds of gram scale quantities for pivotal tox and clinical studies. Here is a cancer immunotherapy effect of SDC-1801, our preclinical development candidate for cancer and immuno-oncology, data that we presented at EORTC in 2019. In the right-hand plot, we see significant tumor reduction in the syngeneic model of pancreatic cancer in immune-content mice. In contrast, in the left-hand plot, there is very little effect in immune-deficient mice. So the efficacy must be through immune system modulation. We also see similar effects in models of kidney, colon and skin cancers as well as in lymphoma. And we also see additive effects in combination with standard of care chemo and targeted therapies with no additional tox. We're working our way through the preclinical tox studies of SDC-1802. And the manufacturing route, which is very similar to SDC-1801, is almost completed. Moving on to the role of TYK2 and JAK1 in the cytokine storm over reaction to viral infections. We've noted a growing body of literature evidence to support the potential of a selective TYK2/JAK1 inhibitor to be an effective therapy here. COVID-19 and other viral diseases can be fatal due to the cytokine storm overreaction of the immune system that can severely damage the lungs and other organs and be made worse by secondary bacterial pneumonia. Most of the key cytokines found elevated in COVID-19 patients that have been admitted to intensive care, including interleukins 2, 7 and 10 and GCSF, signaled by JAK family kinases. Novartis, Pfizer and Lilly have recently announced plans to trial their JAK1 JAK2 or JAK1 JAK3 inhibitors, ruxolitinib, tofacitinib and baricitinib in COVID-19 patients, and reduced mortality and time to recovery was reported from the baricitinib trial. Viral lung diseases can also lead to secondary bacterial infections such as pneumonia, causing further complications in patients with severe COVID-19. There's good evidence in the literature that TYK2 and JAK1 inhibition should restore the body's protection against these bacterial infections, whereas the JAK inhibition by baricitinib, et cetera, is likely to downgrade this defense to bacterial infection. This all points to TYK2/JAK1 inhibitor that is selective against JAK2, being optimally beneficial here, and that's exactly what we've got with our SDC-1801, SDC-1802, and other TYK2/JAK1 inhibitors. We've recently been awarded a grant from UKRI to investigate our TYK2/JAK1 inhibitors in cellular and animal models of COVID in secondary bacterial infection, and we expect to complete these studies by the middle of this year. Okay. That's my presentation completed. Thank you again for watching. We'd be very happy to discuss licensing and funding opportunities with you further. So please contact me on the tim.mitchell@sareum.co.uk e-mail shown here.