IL1R1

NEW YORK, March 13, 2024 /PRNewswire/ -- A certain variant of a key anti-inflammatory gene protects men under age 75 from severe illness and death when hospitalized from Covid-19, a genetic analysis of their blood shows. According to the study authors, the protective gene in question, an interleukin-1 receptor antagonist (IL1RN) variant, appears to tamp down inflammation. Inflammation is the body's normal reaction to infection, but when unchecked, inflammation can go too far and damage tissues as part of many diseases, including in severe cases of infection with the pandemic virus SARS-CoV-2. Published as a "major article" in The Journal of Infectious Diseases online March 13, the study showed that 124 men between the ages of 19 and 74 who possessed the IL1RN variant, called rs419598, were less likely to become severely ill after hospitalization for Covid-19, and 80% less likely to die from the disease. IL1RN is expressed naturally in the body. Different types of interleukin genes are known to dial inflammation up or down in the context of arthritis, and researchers say the results of the current study suggest that a similar dynamic influences the interleukin-1-related inflammation seen in Covid-19 patients. The findings, from researchers at NYU Grossman School of Medicine, stand out because historically more men than women are known to die from Covid-19, and the IL1RN rs419598 variant appears to selectively protect only men up to age 74, but not beyond that as age-related chronic illnesses unfold. The research team used sequencing technologies for the study to determine the presence of specific genes or variations in the letter code that makes up genes in blood samples from 2,589 men and women hospitalized for Covid-19 at NYU Langone's Tisch Hospital in Manhattan from March 2020 to March 2021. More than half of the men and women in the study were older than age 60 and obese, factors that are known to increase the risk of death from the viral infection. Overall, more men than women (240 men, at 60.5%; and 157 women, at 39.5%) died from their disease, with women 20% less likely to die than men. "Our study results show that among hospitalized patients, while women are still overall less likely than men to die from Covid-19, those men age 74 and younger who possess the IL1RN gene variant rs419598 are much less likely to suffer the severe inflammation tied to SARS-CoV-2 infection and less likely to die from the disease," said study colead investigator and molecular biologist Mukundan Attur, PhD. Attur is an associate professor in the Department of Medicine at NYU Langone Health. Among the study's other findings was that average blood levels of the anti-inflammatory protein IL-1Ra, coded by IL1RN, were 14 times higher in 181 hospitalized men than in healthy male study controls from the general population, and 10 times as high in 178 hospitalized women than in healthy females. However, researchers say the increased levels of IL-1Ra in women did not result in any statistically significant reductions in death. "Our analysis offers substantial evidence of the biological link between the severe inflammation seen in SARS-CoV-2 and that which occurs in rheumatoid arthritis," said study senior investigator Steven Abramson, MD, the Frederick H. King Professor of Internal Medicine at NYU Langone. Abramson, a rheumatologist who also serves as chair of the Department of Medicine and chief academic officer at NYU Langone, says previous research has shown that such rheumatoid inflammation is lower in people who possessed one of the three IL1RN variants analyzed in the study. More importantly, Abramson says, the new research suggests that restraining the interleukin-1 biological pathway, which is in part tamped down by the anti-inflammatory protein IL-1Ra, could help prevent the severe inflammation seen in SARS-CoV-2 infection. Further research, he says, is warranted into whether IL-1-inhibiting therapies, such as the IL1 receptor antagonists anakinra, canakinumab, and rilonacept, are effective against Covid infection. Abramson already has plans to investigate if the IL-1 pathway plays a role in long Covid, when people experience new or lingering symptoms, such as fatigue and "brain fog," months after recuperating from their initial infection. Abramson points out that the new study adds to the growing scientific evidence about the biological factors that contribute to gender differences seen in deaths from Covid-19, which are known to vary widely across the United States. Funding support for this study was provided by National Institutes of Health grants P30CA016087 and R21AR078466. Besides Abramson and Attur, other NYU Langone researchers involved in this study are co-lead investigators Christopher Petrilli, MD, and Samrachana Adhikari, PhD, and study co-investigators Eduardo Iturrate, MD; Xiyue Li, MS; Stephanie Tuminello, MPH; Nan Hu, MS; Aravinda Chakravarti, PhD; and David Beck, MD, PhD. STUDY LINK: Media Inquiries: David March 212-404-3528 [email protected] SOURCE NYU Langone Health System

Preliminary fourth quarter 2023 total revenue of approximately $35.7 million which includes record TAVALISSE® net product sales of $25.7 million and REZLIDHIA® net product sales of $3.9 million Strategic alliance with MD Anderson to advance REZLIDHIA in AML and other cancers Collaboration with CONNECT to evaluate REZLIDHIA in a Phase 2 clinical trial in glioma SOUTH SAN FRANCISCO, Calif., Jan. 8, 2024 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today provided a business update including preliminary total revenue for the fourth quarter of 2023, ongoing activity from the commercial portfolio, including TAVALISSE® (fostamatinib disodium hexahydrate) tablets and REZLIDHIA® (olutasidenib) capsules, and upcoming catalysts for 2024. "2023 was a year of significant growth across our commercial hematology-oncology portfolio. We grew TAVALISSE net product sales nearly 24% over 2022 and successfully achieved more than $10 million of REZLIDHIA revenue during its first full year of launch. This enabled us to generate more than $104 million of total net product sales this year," said Raul Rodriguez, Rigel's president and CEO. "Also, our recent collaborations with MD Anderson and CONNECT will allow us to evaluate the potential of REZLIDHIA as a possible therapy in a broad range of IDH1-mutant cancers. As we head into the future, we are focused on commercial execution, the advancement of our hematology-oncology pipeline, and our plan to reach financial breakeven." Commercial and Preliminary Financial Update In the fourth quarter of 2023, a total of 2,671 bottles of TAVALISSE were sold in the U.S., of which, 2,463 bottles were shipped directly to patients and clinics, representing the highest daily bottles shipped to patients and clinics in a quarter since launch. While Rigel is still determining final results for the fourth quarter of 2023, it expects to report net product sales of TAVALISSE of $25.7 million for the fourth quarter compared to $21.9 million for the same period of 2022. In the fourth quarter of 2023, a total of 308 bottles of REZLIDHIA were sold in the U.S., of which, 278 bottles were shipped directly to patients and clinics. While Rigel is still determining final results for the fourth quarter of 2023, it expects to report net product sales of REZLIDHIA of $3.9 million for the fourth quarter compared to $0.9 million for the same period of 2022. Overall, Rigel expects to report net product sales of $104.3 million in 2023, representing 36% growth over 2022. Contract revenues for the fourth quarter of 2023 are expected to be approximately $6.1 million, consisting of $6.0 million in contract revenue from collaborations and $0.1 million in government contract revenue. Contract revenue from collaborations is expected to include $3.7 million of revenue from Grifols S.A., related to delivery of drug supplies and earned royalties, as well as $2.2 million of revenue from Kissei Pharmaceutical Co., Ltd. and $0.1 million of revenue from Medison Pharma Trading AG, related to delivery of drug supplies. For the fourth quarter of 2023, Rigel expects to report total revenue of approximately $35.7 million. Rigel expects to report cash, cash equivalents, and short-term investments of approximately $56.9 million as of December 31, 2023, compared to $58.2 million as of December 31, 2022. The above information is preliminary, has not been audited, and is subject to change upon the audit of Rigel's financial statements for the year ended December 31, 2023. Rigel expects to provide complete fourth quarter and full year 2023 financial results in March 2024. Q4 Business Update Rigel and The University of Texas MD Anderson Cancer Center (MD Anderson) recently announced a multi-year strategic development collaboration to expand the evaluation of REZLIDHIA (olutasidenib) in acute myeloid leukemia (AML) and other hematologic cancers. Under the strategic collaboration, Rigel and MD Anderson will evaluate the potential of olutasidenib to treat newly diagnosed and relapsed or refractory (R/R) patients with AML, higher-risk myelodysplastic syndromes (MDS), and advanced myeloproliferative neoplasms (MPN), in combination with other agents. The collaboration will also support the evaluation of olutasidenib as monotherapy in lower-risk MDS and maintenance therapy in post-hematopoietic stem cell transplant (HSCT) patients. Rigel will provide $15 million in time-based milestone payments and study material over the five-year collaboration. Rigel and CONNECT recently announced a collaboration to evaluate REZLIDHIA (olutasidenib) in combination with temozolomide as maintenance therapy in patients with high-grade glioma (HGG) harboring an isocitrate dehydrogenase-1 (IDH1) mutation. Under the collaboration, CONNECT will include olutasidenib in CONNECT's TarGeT-D, a molecularly guided Phase 2 umbrella clinical trial for HGG. The Rigel-sponsored arm will study post-radiotherapy administration of olutasidenib in combination with temozolomide followed by olutasidenib monotherapy as maintenance treatment in newly diagnosed pediatric and young adult patients (<39 years old) with IDH1 mutation positive HGG, including diffuse intrinsic pontine glioma (DIPG), an aggressive brain tumor with limited treatment options. Rigel will provide funding up to $3 million and study material over the four-year collaboration. In December 2023, Rigel presented four posters highlighting data from the Company's commercial and clinical-stage hematology-oncology portfolio at the 65th American Society of Hematology Annual Meeting and Exposition. Included was a poster, Abstract #2888, reporting post hoc analyses in a subset of patients with mIDH1 R/R AML or MDS that were R/R to HSCT, ivosidenib, or venetoclax. The analyses suggest that olutasidenib alone or in combination with azacitidine may induce complete remissions in these patients. Rigel continues to advance its open-label, Phase 1b clinical trial of R2891, an investigational, potent, and selective IRAK1/4 inhibitor, in patients with lower-risk myeloid dysplastic syndrome (LR-MDS) who are refractory/resistant to prior therapies. The primary endpoint for this trial is safety with key secondary endpoints including preliminary efficacy and evaluation of pharmacokinetic properties. Rigel is currently enrolling patients in the third cohort. About ITP In patients with ITP (immune thrombocytopenia), the immune system attacks and destroys the body's own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPO-RAs), and splenectomy. However, not all patients respond to existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP. About AML Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that in the United States alone, there were about 20,380 new cases, most in adults, in 2023.2 Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.3 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.4 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need. About R289 R289 is a prodrug of R835, an IRAK1/4 dual inhibitor, which has been shown in preclinical studies to block inflammatory cytokine production in response to toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family signaling. TLRs and IL-1Rs play a critical role in the innate immune response and dysregulation of these pathways can lead to various inflammatory conditions. Chronic stimulation of both these receptor systems is thought to cause the pro-inflammatory environment in the bone marrow responsible for persistent cytopenias in lower-risk MDS patients.5 About TAVALISSE® Indication TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Important Safety Information Warnings and Precautions Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required. Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to ≥3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation. Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE. Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation. TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose. Drug Interactions Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose. It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406. Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug. Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug. Adverse Reactions Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%). Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia. Please see for Full Prescribing Information. To report side effects of prescription drugs to the FDA, visit or call 1-800-FDA-1088 (800-332-1088). TAVALISSE is a registered trademark of Rigel Pharmaceuticals, Inc. About REZLIDHIA® INDICATION REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Differentiation Syndrome REZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis. If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms. Differentiation syndrome may recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction based on recurrence. Hepatotoxicity REZLIDHIA can cause hepatotoxicity, presenting as increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood alkaline phosphatase, and/or elevated bilirubin. Of 153 patients with relapsed or refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients; 13% experienced grade 3 or 4 hepatotoxicity. One patient treated with REZLIDHIA in combination with azacitidine in the clinical trial, a combination for which REZLIDHIA is not indicated, died from complications of drug-induced liver injury. The median time to onset of hepatotoxicity in patients with relapsed or refractory AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to 17 months). The most common hepatotoxicities were elevations of ALT, AST, blood alkaline phosphatase, and blood bilirubin. Monitor patients frequently for clinical symptoms of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Obtain baseline liver function tests prior to initiation of REZLIDHIA, at least once weekly for the first two months, once every other week for the third month, once in the fourth month, and once every other month for the duration of therapy. If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue REZLIDHIA based on recurrence/severity. ADVERSE REACTIONS The most common (≥20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis. DRUG INTERACTIONS Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers. Avoid concomitant use of REZLIDHIA with sensitive CYP3A substrates unless otherwise instructed in the substrates prescribing information. If concomitant use is unavoidable, monitor patients for loss of therapeutic effect of these drugs. LACTATION Advise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose. GERIATRIC USE No overall differences in effectiveness were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase in incidence of hepatotoxicity and hypertension was observed in patients ≥65 years of age. HEPATIC IMPAIRMENT In patients with mild or moderate hepatic impairment, closely monitor for increased probability of differentiation syndrome. Click here for Full Prescribing Information, including Boxed WARNING. To report side effects of prescription drugs to the FDA, visit or call 1-800-FDA-1088 (800-332-1088). REZLIDHIA is a registered trademark of Rigel Pharmaceuticals, Inc. About Rigel Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Founded in 1996, Rigel is based in South San Francisco, California. For more information on Rigel, the Company's marketed products and pipeline of potential products, visit . R289 is an investigational compound not approved by the FDA. The American Cancer Society. Key Statistics for Acute Myeloid Leukemia (AML). Revised January 12, 2023. Accessed Feb. 15, 2023: Leukaemia Care. Relapse in Acute Myeloid Leukaemia (AML). Version 3. Reviewed October 2021. Accessed Feb 15, 2023: Thol F, Schlenk RF, Heuser M, Ganser A. How I treat refractory and early relapsed acute myeloid leukemia. Blood (2015) 126 (3): 319-27. doi: Sallman DA et al. Unraveling the Pathogenesis of MDS: The NLRP3 Inflammasome and Pyroptosis Drive the MDS Phenotype. Front Oncol. June 16, 2016. DOI: Forward Looking Statements This press release contains forward-looking statements relating to, among other things, expected commercial and financial results for the fourth quarter and fiscal year ended December 31, 2023, expectations related to the potential and market opportunity of olutasidenib as therapeutics for R/R AML and other conditions, the commercialization of fostamatinib or olutasidenib in the U.S. and international markets, and Rigel's ability to further develop its clinical stage product candidates and Rigel's partnering and collaboration efforts, including the progress of Phase 1b clinical trial of R289 for the treatment of lower-risk myeloid dysplastic syndrome, olutasidenib's evaluation in acute myeloid leukemia (AML) and other hematologic cancers, and in newly diagnosed pediatric and young adult patients with high-grade glioma (HGG) harboring an isocitrate dehydrogenase-1 (IDH1) mutation. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements can be identified by words such as "plan", "potential", "may", "expects", "will" and similar expressions in reference to future periods. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Rigel's current beliefs, expectations, and assumptions and hence they inherently involve significant risks, uncertainties and changes in circumstances that are difficult to predict and many of which are outside of our control. Therefore, you should not rely on any of these forward-looking statements. Actual results and the timing of events could differ materially from those anticipated in such forward looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the commercialization and marketing of fostamatinib or olutasidenib; risks that the FDA, European Medicines Agency, PMDA or other regulatory authorities may make adverse decisions regarding fostamatinib or olutasidenib; risks that clinical trials may not be predictive of real-world results or of results in subsequent clinical trials; risks that fostamatinib or olutasidenib may have unintended side effects, adverse reactions or incidents of misuses; the availability of resources to develop Rigel's product candidates; market competition; as well as other risks detailed from time to time in Rigel's reports filed with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 and subsequent filings. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. Rigel does not undertake any obligation to update forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise, and expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein, except as required by law. Contact for Investors & Media: Investors: Rigel Pharmaceuticals, Inc. 650.624.1232 ir@rigel.com Media: David Rosen Argot Partners 212.600.1902 david.rosen@argotpartners.com View original content to download multimedia: SOURCE Rigel Pharmaceuticals, Inc. Company Codes: NASDAQ-NMS:RIGL

Company’s focus on advancing first-in-class oral degraders with biologics-like activity to address areas of significant patient need and market potential STAT6 oral degrader KT-621, with dupilumab-like activity, expected to enter Phase 1 clinical trial in the second half of 2024 TYK2 oral degrader KT-294, with a TYK2 loss-of-function profile and expected biologics-like activity, planned to enter Phase 1 clinical trial in the first half of 2025 IRAK4 oral degrader KT-474 (SAR444656) expected to complete enrollment in both Phase 2 HS and AD studies in fourth quarter of 2024, with topline data expected in the first half of 2025 Company to hold virtual Immunology R&D Day webcast today at 10:00 AM ET WATERTOWN, Mass., Jan. 04, 2024 (GLOBE NEWSWIRE) -- Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage biopharmaceutical company advancing a new class of small molecule medicines using targeted protein degradation (TPD), today will share an overview of its strategy to build the industry leading immunology pipeline of oral degrader medicines that target validated pathways and demonstrate efficacy comparable to biologic therapies. As part of its strategy, Kymera is unveiling two new programs that each have the potential to address multiple immune-mediated diseases, each with considerable market potential. The new programs target STAT6, the obligate and specific transcription factor of the IL-4/13 pathway, and TYK2, the key scaffolding kinase of the IL-23/IFN pathways. These represent two essential signaling nodes in genetically and clinically validated pathways driving inflammation in autoimmune diseases that are undrugged or inadequately drugged with other technologies. Kymera will share its immunology strategy, including market insights, program updates, new preclinical data and development timelines, at its virtual R&D Day this morning. “We believe that Kymera is on the way to revolutionizing the treatment of complex immuno-inflammatory diseases by leveraging our disease agnostic platform to build a best-in-industry pipeline of oral immunology medicines with biologics-like efficacy and enormous market potential,” said Nello Mainolfi, Ph.D., Founder, President and CEO, Kymera Therapeutics. “With critical insights from our KT-474 program, a unique target selection strategy and the ability to block key, validated pathways with a degrader approach that has the potential to be superior to traditional small molecules and comparable to approved biologics, we can deliver on our vision to create transformative therapies that will expand the number of patients who can be treated.” The R&D Day presentation will focus on three first-in-class oral degrader immunology programs, including Kymera’s new, wholly-owned STAT6 (KT-621) and TYK2 (KT-294) degraders and its IRAK4 degrader (KT-474): KT-621 (STAT6): STAT6 is an essential transcription factor specific to the IL-4/IL-13 signaling pathway and the central driver of Type 2 inflammation in allergic diseases. STAT6 is a genetically validated target and the pathway has been clinically validated by approved IL-4/IL-13-targeting biologics, including dupilumab. In preclinical studies, KT-621, Kymera’s first-in-class oral STAT6 degrader, demonstrated full inhibition of the IL-4/IL-13 pathway in all relevant human cell contexts with picomolar potency that was superior to dupilumab, and equivalent or superior efficacy to dupilumab in multiple preclinical efficacy studies. In addition, at low oral doses, KT-621 demonstrated near full in vivo STAT6 degradation and was well-tolerated in multiple preclinical toxicity studies. KT-621, a once daily oral small molecule degrader with a preclinical biologics-like efficacy profile, has the potential to have broad activity across multiple diseases, including atopic dermatitis, asthma, chronic obstructive pulmonary disorder, eosinophilic esophagitis and chronic rhinosinusitis with nasal polyps, among others. The Company expects to initiate a Phase 1 clinical trial in the second half of 2024 and report the Phase 1 results in 2025. KT-294 (TYK2): TYK2 is a member of the Janus Kinase (JAK) family required for Type I interferon (IFN), IL-12 and IL-23 signaling with both genetic and clinical validation in autoimmune and inflammatory diseases. TYK2 has a well-established scaffolding function that plays a key role in cytokine receptor surface expression and activation. In preclinical studies, KT-294, Kymera’s first-in-class oral TYK2 degrader, demonstrated picomolar to nanomolar potencies across all relevant human cell contexts evaluated, representing what Kymera believes is the only approach to TYK2 targeting that has the potential to recapitulate the human loss-of-function biology of near full pathway inhibition of Type I IFN, IL-12 and IL-23, while also sparing IL-10. Degradation of TYK2 has the potential to overcome the challenges of small molecule inhibitors, which have limitations due to lack of selectivity, limited target engagement, and/or lack of potent activity against Type I IFN. KT-294, a once daily oral small molecule degrader with a potential biologics-like efficacy profile, has the opportunity to address conditions such as inflammatory bowel disease, psoriasis, psoriatic arthritis and lupus, among others. Kymera intends to initiate a Phase 1 clinical trial in the first half of 2025 and report the Phase 1 results in 2025. KT-474/SAR444656 (IRAK4): KT-474 is a first-in-class IRAK4 degrader in Phase 2 clinical trials for the treatment of hidradenitis suppurativa (HS) and atopic dermatitis (AD). IRAK4 is a key scaffolding protein of the myddosome complex that mediates signaling through IL-1 receptors (IL-1R) and toll-like receptors (TLR), which play a crucial role in inflammation across multiple autoimmune diseases. In a Phase 1 trial published last November in Nature Medicine, KT-474 demonstrated robust degradation of IRAK4 in the blood and skin of healthy volunteers and patients with HS and AD, which was associated with a systemic anti-inflammatory effect and preliminary evidence of clinical activity. Enrollment in both Phase 2 trials is ongoing and anticipated to be completed in the fourth quarter of 2024, with topline data expected in the first half of 2025. Kymera is collaborating with Sanofi on the development of KT-474. Kymera R&D Day DetailsKymera will host a webcast to discuss its emerging immunology pipeline from 10:00 a.m. – 12:00 p.m. ET, Thursday, January 4, 2024. To join the webcast please use this link. The slide presentation will be available after the prepared remarks and before the question and answer section of the webcast in the “News and Events ” section of the Investors section of the Company’s website at www.kymeratx.com. The replay of the event will be available shortly after the conclusion of the meeting. About Kymera Therapeutics Kymera is a clinical-stage biotechnology company pioneering the field of targeted protein degradation (TPD) to develop medicines that address critical health problems and have the potential to dramatically improve patients’ lives. Kymera is deploying TPD to address disease targets and pathways inaccessible with conventional therapeutics. Having advanced the first degrader into the clinic for immunological diseases, Kymera is focused on delivering oral small molecule degraders to provide a new generation of convenient, highly effective therapies for patients with these conditions. Kymera is also progressing degrader oncology programs that target undrugged or poorly drugged proteins to create new ways to fight cancer. Founded in 2016, Kymera has been recognized as one of Boston’s top workplaces for the past several years. For more information about our science, pipeline and people, please visit www.kymeratx.com or follow us on X (formerly Twitter) or LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements by Kymera Therapeutics regarding its: strategy, business plans and objectives for our clinical stage degrader programs; plans and timelines for the preclinical and clinical development of its product candidates, including the therapeutic potential, clinical benefits and safety thereof; expectations regarding timing, success and data announcements of current ongoing preclinical and clinical trials; the ability to initiate new clinical programs; and Kymera’s financial condition and expected cash runway into the first half of 2026. The words "may," “might,” "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," “expect,” "estimate," “seek,” "predict," “future,” "project," "potential," "continue," "target" and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: the timing and anticipated results of our current and future preclinical studies and clinical trials, supply chain, strategy and future operations; the delay of any current and future preclinical studies or clinical trials or the development of Kymera Therapeutics' drug candidates, including those for KT-474, KT-621, and KT-294; the risk that the results of current preclinical studies and clinical trials may not be predictive of future results in connection with current or future preclinical and clinical trials; Kymera Therapeutics' ability to successfully demonstrate the safety and efficacy of its drug candidates; the timing and outcome of the Kymera Therapeutics' planned interactions with regulatory authorities; obtaining, maintaining and protecting its intellectual property; the risks associated with pandemics or epidemics; and Kymera Therapeutics' relationships with its existing and future collaboration partners. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in the Annual Report on Form 10-K for the period ended December 31, 2022, and Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2023, as well as discussions of potential risks, uncertainties, and other important factors in Kymera Therapeutics' subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Kymera Therapeutics' views only as of today and should not be relied upon as representing its views as of any subsequent date. Kymera Therapeutics explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Investor Contact: Justine KoenigsbergVice President, Investor Relationsinvestors@kymeratx.com857-285-5300Media Contact:Todd CooperSenior Vice President, Corporate Affairsmedia@kymeratx.com857-285-5300