New Phase 3b data on Lilly's Taltz (ixekizumab) and Zepbound (tirzepatide) advance understanding of the interconnected immune and metabolic biology in adults with psoriasis and obesity

Exploratory data presented at Fall Clinical 2026 showed broader biomarker changes with Taltz and Zepbound vs. Taltz alone as early as Week 12 in first-of-its-kind TOGETHER-PsO study

INDIANAPOLIS, Oct. 9, 2026 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced new exploratory data from the TOGETHER-PsO Phase 3b clinical trial evaluating the concomitant use of Taltz (ixekizumab) and Zepbound (tirzepatide) compared with Taltz alone in adults with moderate-to-severe plaque psoriasis and obesity or overweight with at least one additional weight-related comorbid condition. The prespecified analysis, presented at the 2026 Fall Clinical Dermatology Conference in Las Vegas, provides new insights suggesting an immunometabolic relationship between psoriasis and obesity. These data showed that when Taltz and Zepbound were used together, changes were observed in more psoriasis disease-associated and metabolic biomarkers compared to Taltz monotherapy. In the U.S., approximately 61% of people with psoriasis also have obesity or overweight with at least one weight-related comorbidity. 1

"People living with psoriasis and obesity carry a compounded burden that extends beyond what is visible, yet these conditions are too often viewed through separate treatment lenses," said Mark Genovese, M.D., senior vice president of Lilly Immunology development. "The broader biomarker changes observed with Taltz and Zepbound, including those associated with skin clearance, may point to a meaningful relationship between immune and metabolic biology. Along with previously reported clinical outcomes, these findings support a more comprehensive approach to psoriasis care that also addresses obesity for people managing both conditions."

This analysis examined circulating proteins and gene expression in the blood to better understand the biological change observed when patients were treated concomitantly with Taltz and Zepbound vs. Taltz alone. At Week 36, observed changes in psoriasis-specific, immune and metabolic biomarkers in both the Taltz and Zepbound and Taltz monotherapy treatment arms were consistent with the known biological effects of each medicine when used for their approved indications. Notably, Taltz and Zepbound used together were associated with broader biomarker responses compared to Taltz alone as early as Week 12. This included changes in more proteins (482 vs. 140 differentially expressed proteins) and genes (467 vs. 16 differentially expressed genes) by Week 36.

Further, the analysis showed greater reductions in inflammatory immune activity with Taltz and Zepbound compared with Taltz alone, including changes related to neutrophils, a type of immune cell involved in inflammation. Changes in a subset of neutrophil-associated markers mediated a portion of the additional Psoriasis Area and Severity Index (PASI) response seen with Taltz and Zepbound vs. Taltz alone.

"This analysis provides new insights into the potential connected immune and metabolic biology in people with psoriasis and obesity," said James G. Krueger, M.D., Ph.D., Professor and Laboratory Head, The Rockefeller University. "What is most compelling is these findings identified differences in inflammatory pathways when patients received concomitant treatment with Taltz plus Zepbound for both conditions. These data at the intersection of psoriasis and obesity highlight immunometabolic health as an important area for continued scientific research."

These data follow previously reported results from TOGETHER-PsO, which showed that Taltz and Zepbound used together delivered superior skin clearance and clinically meaningful weight reduction compared with Taltz alone at the Week 36 primary endpoint. Improvements were maintained or further improved through Week 52, with safety consistent with the known profile of each respective medicine.

About the TOGETHER-PsO trial TOGETHER-PsO (NCT06588283) is a 52-week Phase 3b, randomized, multicenter, assessor-blinded, open-label study assessing the efficacy and safety of concomitant administration of Taltz and Zepbound compared with Taltz alone in adults with moderate-to-severe plaque psoriasis and obesity or overweight (BMI ≥30 kg/m², or ≥27 to <30 kg/m²) with at least one additional weight-related comorbid condition. A total of 274 participants were randomized 1:1 to receive either Taltz alone or concomitantly with Zepbound, both administered subcutaneously. Patients in both arms received counseling on a reduced-calorie diet and increased physical activity. The primary endpoint is to assess the proportion of participants achieving both Psoriasis Area and Severity Index (PASI) 100 and ≥10% weight reduction at Week 36.

About Taltz (ixekizumab) Taltz is a monoclonal antibody that selectively binds with interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Taltz inhibits the release of pro-inflammatory cytokines and chemokines. Taltz is approved to treat adults with active psoriatic arthritis and adults and children 6 years and older with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Additionally, Taltz is approved for adults with active ankylosing spondylitis, and adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation.

About Zepbound (tirzepatide) injection Zepbound (tirzepatide) is the first and only dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist obesity medication. Zepbound tackles an underlying cause of excess weight. It reduces appetite and how much you eat. Zepbound is indicated for adults with obesity, or some adults who are overweight and also have at least one weight-related medical problem, to lose weight and keep it off. Additionally, Zepbound is FDA-approved to treat adults with moderate-to-severe obstructive sleep apnea and obesity. Zepbound should be used with a reduced calorie diet and increased physical activity.

• People 6 years of age and older with moderate to severe plaque psoriasis who may benefit from taking injections or pills (systemic therapy) or treatment using ultraviolet or UV light (phototherapy).

• Adults with active psoriatic arthritis.

• Adults with active ankylosing spondylitis.

• Adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation.

It is not known if Taltz is safe and effective in children for conditions other than plaque psoriasis or in children under 6 years of age.

Warnings - Taltz affects the immune system. It may increase your risk of infections, some people have had serious infections, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have been hospitalized from these infections. Do not use Taltz if you have any symptoms of infection, unless your doctor tells you to. If you have a symptom after starting Taltz, call your doctor right away.

Your doctor should check you for TB before you start Taltz, and watch you closely for signs of TB during and after treatment with Taltz. If you have TB, or had it in the past, your doctor may treat you for it before you start Taltz.

Do not use Taltz if you have had a serious allergic reaction to ixekizumab or any other ingredient in Taltz, such as: swelling of your eyelids, lips, mouth, tongue or throat, trouble breathing, feeling faint, throat or chest tightness, or skin rash. Get emergency help right away if you have any of these reactions. See the Medication Guide that comes with Taltz for a list of ingredients.

Severe skin reactions that look like eczema can happen during treatment with Taltz from days to months after your first dose and can sometimes lead to hospitalization. Your doctor may temporarily stop treatment with Taltz if you develop severe skin reactions. Tell your doctor if you have any of the following: redness or rash, itching, patches, your skin is dry or feels like leather, blisters or abrasions that ooze or become crusty, small bumps or plaques with scale or crusting.

Crohn's disease or ulcerative colitis (inflammatory bowel disease) can start or get worse with Taltz use. Tell your doctor if you have any of these symptoms or if they get worse: stomach pain, diarrhea, and weight loss.

You should not get live vaccines while taking Taltz. You should get the vaccines you need before you start Taltz.

• Injection site reactions

• Nausea

• Upper respiratory infections

• Fungal skin infections

Tell your doctor if you have any side effects. You can report side effects at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Are you being treated for an infection?

• Do you have an infection that does not go away or keeps coming back?

• Do you have TB or have you been in close contact with someone with TB?

• Do you have possible symptoms of an infection such as fever, cough, sores, diarrhea, or other symptoms? Ask your doctor about other possible symptoms.

• Do you have Crohn's disease or ulcerative colitis?

• You need any vaccines or have had one recently.

• You take prescription or over-the-counter medicines, vitamins, or herbal supplements.

• You are pregnant or planning to become pregnant. It is not known if Taltz can harm an unborn baby.

• Pregnancy Exposure Registry: There is a pregnancy registry to collect information about women who are exposed to Taltz during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. If you become pregnant while taking Taltz, you are encouraged to enroll in the pregnancy registry by calling 1-800-284-1695 or by visiting online at http://www.pregnancyregistry.lilly.com.

• You are breastfeeding or planning to breastfeed. It is not known if Taltz passes into breastmilk.

How to take See the instructions for use that come with Taltz. There you will find information about how to store, prepare, and inject Taltz. Adults may self-inject after receiving training from a healthcare provider.

For children 6 to 17 years of age:

• If your child's healthcare provider decides that you may give Taltz injections at home, you should receive training on the right way to prepare and inject Taltz. Do not try to give Taltz to your child until you have been shown how to inject Taltz. Children should not inject themselves with Taltz. You or an adult caregiver should prepare and give Taltz injections to your child.

Learn more Taltz is a prescription medicine available as a 80 mg/mL, 40 mg/0.5mL, 20 mg/0.25mL injection. For more information, call 1-800-545-5979 or go to taltz.lilly.com.

This summary provides basic information about Taltz but does not include all information known about this medicine. Read the information that comes with your prescription each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other healthcare provider about Taltz and how to take it. Your doctor is the best person to help you decide if Taltz is right for you.

IX CON BS 20AUG2024

U.S. ZEPBOUND INDICATIONS AND SAFETY SUMMARY WITH WARNINGS Zepbound ® (ZEHP-bownd) is an injectable prescription medicine used with a reduced-calorie diet and increased physical activity to help adults with:

• obesity, or some adults with overweight who also have weight-related medical problems, to lose excess body weight and keep the weight off.

• moderate-to-severe obstructive sleep apnea (OSA) and obesity to improve their OSA.

Zepbound contains tirzepatide and should not be used with other tirzepatide-containing products or any GLP-1 receptor agonist medicines. It is not known if Zepbound is safe and effective for use in children.

Warnings - Zepbound may cause tumors in the thyroid, including thyroid cancer. Watch for possible symptoms, such as a lump or swelling in the neck, hoarseness, trouble swallowing, or shortness of breath. If you have any of these symptoms, tell your healthcare provider.

• Do not use Zepbound if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC).

• Do not use Zepbound if you have Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

• Do not use Zepbound if you have had a serious allergic reaction to tirzepatide or any of the ingredients in Zepbound.

KwikPen ®: Do not share your KwikPen with other people, even if the pen needle has been changed. You may give other people a serious infection or get a serious infection from them.

Severe stomach problems. Stomach problems, sometimes severe, have been reported in people who use Zepbound. Tell your healthcare provider if you have stomach problems that are severe or will not go away.

Dehydration leading to kidney problems. Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems. It is important for you to drink fluids to help reduce your chance of dehydration. Tell your healthcare provider right away if you have nausea, vomiting, or diarrhea that does not go away.

Gallbladder problems. Gallbladder problems have happened in some people who use Zepbound. Tell your healthcare provider right away if you get symptoms of gallbladder problems, which may include pain in your upper stomach (abdomen), fever, yellowing of skin or eyes (jaundice), or clay-colored stools.

Inflammation of the pancreas (pancreatitis). Stop using Zepbound and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without nausea or vomiting. You may feel the pain from your abdomen to your back.

Serious allergic reactions. Stop using Zepbound and get medical help right away if you have any symptoms of a serious allergic reaction, including swelling of your face, lips, tongue or throat, problems breathing or swallowing, severe rash or itching, fainting or feeling dizzy, or very rapid heartbeat.

Low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use Zepbound with medicines that can cause low blood sugar, such as a sulfonylurea or insulin.

Signs and symptoms of low blood sugar may include dizziness or light-headedness, sweating, confusion or drowsiness, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability, mood changes, hunger, weakness or feeling jittery.

Food or liquid getting into the lungs during surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). Zepbound may increase the chance of food getting into your lungs during surgery or other procedures. Tell all your healthcare providers that you are taking Zepbound before you are scheduled to have surgery or other procedures.

Common side effects The most common side effects of Zepbound include nausea, diarrhea, vomiting, constipation, stomach (abdominal) pain, indigestion, injection site reactions, feeling tired, allergic reactions, belching, hair loss, and heartburn. These are not all the possible side effects of Zepbound. Talk to your healthcare provider about any side effect that bothers you or doesn't go away.

Tell your doctor if you have any side effects. You can report side effects at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Your healthcare provider should show you how to use Zepbound before you use it for the first time.

• Talk to your healthcare provider about low blood sugar and how to manage it. Tell your healthcare provider if you are taking medicines to treat diabetes including an insulin or sulfonylurea.

• If you take birth control pills by mouth, talk to your healthcare provider before you use Zepbound. Birth control pills may not work as well while using Zepbound. Your healthcare provider may recommend another type of birth control for 4 weeks after you start Zepbound and for 4 weeks after each increase in your dose of Zepbound.

Review these questions with your healthcare provider: ❑ Do you have other medical conditions, including problems with your pancreas, or severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems digesting food? ❑ Do you take diabetes medicines, such as insulin or sulfonylureas? ❑ Do you have a history of diabetic retinopathy? ❑ Are you scheduled to have surgery or other procedures that use anesthesia or deep sleepiness (deep sedation)? ❑ Do you take any other prescription medicines or over-the-counter drugs, vitamins, or herbal supplements? ❑ Are you pregnant, plan to become pregnant, breastfeeding, or plan to breastfeed? Zepbound may harm your unborn baby. Tell your healthcare provider if you become pregnant while using Zepbound. Zepbound may pass into your breast milk. You should talk with your healthcare provider about the best way to feed your baby while using Zepbound.

• Pregnancy Exposure Registry: There is a pregnancy exposure registry for women who have taken Zepbound during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry, or you may call 1-844-524-0039 or email at [email protected] or visit https://pregnancyregistry.lilly.com/zepbound.

• Read the Instructions for Use that come with Zepbound.

• Use Zepbound exactly as your healthcare provider says.

• Use Zepbound with a reduced-calorie diet and increased physical activity.

• Inject Zepbound under the skin (subcutaneously) of your stomach (abdomen), thigh, or have another person inject in the back of the upper arm. Do not inject ZEPBOUND into a muscle (intramuscularly) or vein (intravenously).

• Use Zepbound 1 time each week, at any time of the day.

• Change (rotate) your injection site with each weekly injection. Do not use the same site for each injection.

If you take too much Zepbound, call your healthcare provider, call the Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.

This summary provides basic information about Zepbound but does not include all information known about this medicine. Read the information that comes with your prescription each time your prescription is filled. This information does not take the place of talking with your healthcare provider. Be sure to talk to your healthcare provider about Zepbound and how to take it. Your healthcare provider is the best person to help you decide if Zepbound is right for you.

ZP CON BS 01SEP2026

Zepbound ®, its delivery device base and KwikPen ® are registered trademarks owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.

About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram, and LinkedIn. P-LLY

Trademarks and Trade Names All trademarks or trade names referred to in this press release are the property of the company, or, to the extent trademarks or trade names belonging to other companies are referenced in this press release, the property of their respective owners. Solely for convenience, the trademarks and trade names in this press release are referred to without the ® and ™ symbols, but such references should not be construed as any indicator that the company or, to the extent applicable, their respective owners will not assert, to the fullest extent under applicable law, the company's or their rights thereto. We do not intend the use or display of other companies' trademarks and trade names to imply a relationship with, or endorsement or sponsorship of us by, any other companies.

Cautionary Statement Regarding Forward-Looking Statements This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Taltz (ixekizumab) as a treatment for psoriasis and Zepbound (tirzepatide) as a treatment for adults with obesity or overweight, and potential comprehensive treatment strategies for patients with psoriasis and obesity, and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development and commercialization. Among other things, there is no guarantee that future study results will be consistent with the results to date, or that Lilly will execute its strategies as planned. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

• Armstrong et al, Addressing the Obesity-Psoriasis Connection: Prevalence, Incidence, and Comorbidity Insights from a Large US Population of 19.9 Million (2018-2024). Presented at Maui Derm, 2026.

Kathleen Ritchie; [email protected] (Media)

Michael Czapar; [email protected] (Investors)