Sareum Holdings plc (SAR) Earnings Call Transcript & Summary

My name is Tim Mitchell and I'm CEO and a founder of Sareum. Thank you for watching Sareum's BioTrinity presentation that will showcase our next-generation TYK2/JAK1 immunotherapeutics and their potential to treat autoimmune diseases, cancer and of particular current interest, the cytokine storm that is often the cause of death in COVID-19 patients. Sareum is an AIM listed company, so first, I need to show this disclaimer. Our business model is to take small molecule inhibitors into preclinical or early clinical development and license them all. This model has been validated by CHK1 kinase cancer program, working with CR U.K. funded organizations. We developed SRA737 and took it into Phase I studies before licensing it to Sierra Oncology in a $328 million deal. A month ago, we also licensed our FLT3 and Aurora kinase program to a Chinese specialty pharma company. 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 cell signaling enzymes, which are important for maintaining a healthy, well balanced immune system. And as such, a target of great interest to pharmaceutical companies. There has been good clinical validation for TYK2 and TYK2/JAK1 inhibitors from BMS and Pfizer in psoriasis. But we believe there's room for improvement. There are also Phase II trials ongoing, again on BMS and Pfizer's, TYK2 and TYK2/JAK1 inhibitors in several other autoimmune diseases, including lupus, ulcerative colitis, Crohn's disease and vitiligo with readouts expected later this year. Although the coronavirus outbreak may delay these timelines. JAK family kinases transmit extracellular signals from cytokines through the stat transcription factors. The cytokine binds through its receptor with each receptor being associated with one or more particular JAK kinase family members. And some of the key cytokines, their receptors and their associated JAKs are shown here. 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 is believed to be responsible for the FDA black box warnings for serious infections, lymphoma and thrombosis that are issued to tofacitinib and baricitinib. Sareum second-generation inhibitors target TYK2 and JAK1, which signal all therapeutically relevant cytokines shown here associated with autoimmune diseases, such as psoriasis, arthritis, IBD and lupus. These inhibitors are very selective against JAK2 and JAK3, so we would not expect to see the series of side effects that can arise from JAK2 and JAK3 inhibition. As well as autoimmune diseases, TYK2 is also associated with cancers, it's oncogenic in T-cell acute lymphoblastic leukemia, and excessive TYK2/JAK1 signaling is associated with several solid tumor types. Very interestingly, we also see the TYK2/JAK1 modulation of the local immune system results in significant tumor reduction in many cancer types. Viral diseases such as COVID-19 and flu can be fatal due to an overreaction of the body's immune system called a cytokine storm. TYK2 and JAK1 play an important role in the cytokine response, and I'll say more about this on a later slide. 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 distinctive TYK2/JAK1 kinase inhibitors, both the potent inhibitors of TYK2 and JAK1 and have selected over JAK2 and JAK3 and the rest of the kinase. We are dosing already twice daily in mouse models, but we believe we will be able to dose once-daily in any human studies. 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 tox studies, we've got up to 30 times the therapeutic dose without reaching an MTD and we're looking to increase this dose even higher in our dose-ranging studies. The synthetic route for SDC-1801 has been developed, and we are able to manufacture hundreds of grams scale quantities for preclinical tox and clinical studies. Here is a cancer immunotherapy effects of SDC-1802, our preclinical development candidate for cancer and immuno-oncology. Data that we presented at EORTC last year. In the right-hand plot, we see significant tumor reduction in the syngeneic model of pancreatic cancer in immunocompetent mice. In contrast, in the left-hand plot, there is very little effect in immunodeficient 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 lymphoma, and we also see additive effects in combination with standard of care chemo and targeted therapies with no additional talks. We're working our way through the preclinical tox studies on SDC-1802 and the manufacturing route, which is very similar to SDC-1801 is almost completed. I thought I'd say more about the TYK2/JAK1 and cytokine storm reaction to viral infections. And here is some literature evidence for 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. Some key cytokines found elevated in COVID-19 patients that have been admitted to intensive care include interleukins 2, 7 and 10 and granulocyte colony-stimulating factor. All of which signaled by JAK Family kinases. Novartis, Pfizer and Lilly have recently announced plans to trial their JAK1/2 or JAK1/3 inhibitors, ruxolitinib, tofacitinib and baricitinib in COVID-19 patients. Secondary bacterial infections, such as pneumonia, can also cause severe complications in patients with viral lung disease. Bacterial infections induce the cytokines, interleukin-1ß, and granulocyte-macrophage colony-stimulating factor, which have a beneficial protective effect against the bacterial infection. GM-CSF administration has been reported to improve the outcome in patients with pneumonia associated acute respiratory distress syndrome. Now unfortunately for patients, this IL-1ß GM-CSF pathway is blocked by virally induced interferons alpha and gamma. But as we saw earlier, TYK2 and JAK1 inhibition brought both interferon alpha and interferon gamma signaling, and this blockade has been shown to restore GM-CSF levels in lung infection models. The final piece of this quite complicated jigsaw is that GM-CSF signals via JAK2. So any JAK2 inhibition is unlikely to undo the effects of restoring GM-CSF levels here. This all points to a 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. 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 [email protected] e-mail shown here.