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Endocrinology

Systemic Immune Inflammation Index Predictor for Thyroiditis | IJGM – Dove Medical Press

Introduction

Subacute thyroiditis (SAT) is a self-limiting inflammatory thyroid gland disease and is characterized by a sudden onset of neck pain, fever, and thyrotoxicosis caused by follicular epithelial destruction.1,2 Females between the ages of 30 and 50 are particularly vulnerable. In recent years, significant progress has been demonstrated in SAT pathogenesis, epidemiology, and clinical courses. It is a known fact that, inflammation plays a significant role in the development of SAT. Pathogenesis of SAT depends on genetic background and triggering factors, such as several viral infections, vaccines, and some drugs.3 The disease severity may reach its peak within three to four days and continues with fluctuating intensity for three to six weeks. Pain lasts for a week to a few months. The American Thyroid Association guidelines recommend corticosteroids in moderate/severe SAT. In our clinical practice, either non-steroidal anti-inflammatory agents (NSAIDs) or 1632 mg methylprednisolone (MPS) treatment has been administered depending on the clinicians preference. Clinical diagnosis can be made based on history, physical examination, biochemical evidence of transient thyrotoxicosis, and reduced radio-iodine uptake on radioactive iodine uptake scan.4 A very high (>50 mm/h) erythrocyte sedimentation rate (ESR) is an additional distinctive diagnostic feature in subacute thyroiditis. C-reactive protein (CRP) may also be elevated in many cases. Thyroid ultrasonography demonstrates heterogeneously hypoechoic and suppressed vascular patterns.5

A complete blood cell count provides information on the number and morphology of various cells. Neutrophils, a part of the innate immune system, have been shown to increase and release inflammation mediators in inflammatory conditions such as SAT. However, the mechanism of lymphocytopenia in patients with SAT remains unclear. Virus infection of T cells6 and elevated cortisol levels7 may be potential factors leading to lymphopenia. Platelets are known to have regulatory effects on both the innate and adaptive immune systems and that the various cytokines they secrete in collaboration with neutrophils cause tissue destruction as a result of the activation of more and more neutrophils and platelets. It is involved in the pathogenesis of numerous acute and chronic inflammatory and autoimmune diseases.8,9

There is a growing interest in the discovery of new biomarkers as indicators of inflammation. Several new leukocyte-based inflammatory indicators, including the Systemic Immune Inflammation Index (SII), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and neutrophil-to-lymphocyte ratio (NLR), have recently been used as diagnostic and prognostic predictors of certain diseases. These indicators have also been investigated as biomarkers for inflammatory and rheumatic diseases. SII, which was first developed in 2014, is considered to be more predictive compared to NLR and PLR.10 Besides, it has been shown to be associated with oncological outcomes in several types of cancer.11,12 It is also believed that SII may reflect the balance between host immune and inflammatory conditions.

Considering the research on this matter, our study may be the first one demonstrating the role of SII in the diagnosis and estimating the recovery time of SAT considering treatment.

The primary purpose of the present study is to evaluate the clinical significance of SII regarding recovery time, hypothyroidism, and recurrence rate in patients with SAT and to compare it to other inflammatory markers. Therefore, clinicians may have an idea about the most effective therapeutic choice and its duration by estimating recovery time.

Sixty-nine SAT patients (52 females and 17 males) with no comorbidities and 59 healthy volunteers (43 females and 16 males) admitted to the Outpatient Department of Endocrinology and Metabolism Diseases, Erzurum Training and Research Hospital between November 2021 and June 2022 were involved in this study. SAT was confirmed by typical symptoms, physical examination, increased ESR, elevated free T4 (fT4), decreased TSH, decreased radioactive iodine uptake and presence of hypoechoic areas with blurred margins and decreased vascularization on thyroid ultrasound in all the patients. Considering age and gender factors, there was almost no difference between the patient and control groups. The patients were followed up on 612 months. Anti-inflammatory medication (indomethacin or 1632 mg MPS, depending on their clinical condition) was started for all patients. The dose titration and duration of treatment could be changed according to the patients clinical symptoms. The number of the patients administered indomethacin and MPS was 31 and 38, respectively. Patients below 18 years, pregnant women, patients with chronic diseases such as heart disease, renal failure, hematological diseases, cancer, or rheumatic diseases, and patients receiving medical treatment that may influence the blood system during the preceding three months were excluded from the study.

Biochemical and hematologic tests were studied. Complete blood count parameters white blood cells, platelet count, neutrophil, lymphocyte, and monocyte count were performed with a Sysmex XN 9000 brand autoanalyzer. Other biochemistry parameters were studied with a Cobas C 701 brand biochemistry autoanalyzer (Roche, Germany). TSH and fT4 were measured by the chemiluminescent immunoassay method (Beckman Coulter, DXI 800, Brea, CA, USA). Reference ranges were defined as fT4: 0.891.76 ng/dl, TSH: 0.554.78 mIU/L, ESR: 020 mm/h, and CRP: 05 mg/L.

Novel inflammation parameters were calculated using the formulas NLR = neutrophils / lymphocytes, PLR = platelets / lymphocytes, SII (neuthrophils platelets) / lymphocytes, SLR (ESR lymphocyte rate) = ESR / lymphocytes and CLR (CRP lymphocyte rate) = CRP / lymphocytes.

Theoretically, CRP level increases more rapidly than ESR in early-stage inflammatory diseases and begins to decrease more quickly than ESR. Therefore, we defined the time when the CRP level decreased to normal and the clinical symptoms of patients resolved as the recovery time.

SPSS 22.0 (SPSS Inc., Chicago, IL, USA) statistical software was used for all analyses. The variables were investigated through visual and analytic methods (KolmogorovSmirnov/ShapiroWilk test) to determine whether they were normally distributed or not. Students T-Test and the MannWhitney U-Test were used to compare normally and non-normally distributed variables, respectively. Descriptive analyses were presented using means and standard deviations for normally distributed variables, whereas medians and minimum-maximum were used for non-normally distributed variables. The chi-square test was used to compare categorical variables. On the other hand, the Spearman correlation coefficient was used. P value less than 0.05 was deemed statistically significant.

Table 1 displays the age and gender distributions of the patient and control groups. There was no significant difference in genders or mean ages between the two groups (p>0.05). Neutrophils, monocytes, ESR, CRP, SII, PLR, SLR, CLR, and NLR were found to be significantly higher at the time of diagnosis in the patient group compared to the control group, while LMR was found to be lower. The median recovery period in the study group was thirty-five days (Table 2).

Table 1 The Distribution of Gender and the Means and Standard Deviations of the ParticipantsAge

Table 2 The Medians, Minimum, and Maximum Ranges of Parameters of the SAT Patients at the Time of Diagnosis and Healthy Controls

According to the results of Spearman correlation analysis, a statistically significant positive correlation was detected in SII levels, compared to other inflammation markers like SLR. On the other hand, as expected, there was a statistically significant negative correlation between SII and LMR. Furthermore, our statistical analysis revealed a strong positive correlation between SII and SAT recovery time and a weak-moderate positive correlation between PLR and recovery time (Table 3). According to the correlation analysis between the recovery time and SII based upon the medication administered in the treatment of SAT, a strong positive correlation was detected only in the group given MPS, not in the group given NSAIDs (Table 4). Also, SII levels at the time of diagnosis were already higher in patients receiving MPS (Table 5).

Table 3 Recovery Time Correlations with Other Inflammatory Markers in Patients with Subacute Thyroiditis Using Spearman Correlation Analysis

Table 4 Correlation Analyses Between Systemic Immune Inflammation Index and Recovery Time in Terms of Medical Treatment in Patient Group

Table 5 Comparisons of Some Parameters According to the Type of SAT Treatment

There was no correlation between SII level and ESR, CRP, fT4, or age factor. Hypothyroidism developed in 12 out of 69 patients (17%) during 612 months follow-up period. No significant correlation was detected between the development of hypothyroidism and other parameters such as SII, NLR, LMR, PLR, fT4, CRP/lymphocyte, ESR/lymphocyte, recovery time, and gender factor. Over the course of the follow-up period, only eight (11%) patients in the MPS group had recurrence. No recurrence was observed in the NSAID group (Table 5).

SII levels did not differ between patients developing and not developing recurrence. TSH and ESR levels at the time of diagnosis were higher in patients with recurrence, compared to those without recurrence (Table 6). Considering gender factor, the recurrence rate was 11.8% for males and 11.5% for females.

Table 6 Comparisons of Laboratory Test Results and Recovery Time of the Patients with and Without Recurrence

Subacute thyroiditis is an inflammatory disease with a high inflammatory load that can progress to long-term severe clinical symptoms and significant comorbidity. As can be seen in our study, females between the ages of 30 and 40 are exposed to subacute thyroiditis more frequently, compared to males (a ratio of 3 to 5:1). This inflammatory disease may be diagnosed with medical history and clinical, laboratory, and imaging findings. In the early phase of SAT, almost all patients may have hyperthyroidism and elevated acute-phase reactants. ESR is one of the most widely used laboratory tools for detecting inflammatory syndromes like SAT. However, it is important to take into account all factors that may influence ESR values such as age and gender factors, the lifestyles of patients, and common metabolic abnormalities.13 Occasionally, value discrepancies may be observed between CRP and ESR due to their kinetic differences. To illustrate, CRP level increases faster than ESR level and begins to decrease more quickly. However, whether one over the other or one over two tests combined has a higher predictive value remains debatable.14 Therefore, studies investigating additional parameters to guide diagnosis and prognosis of subacute thyroiditis are ongoing. Although the diagnostic role of ESR and CRP was determined in patients with SAT pursuant to other studies, we found in our study that these parameters were not clinically effective for estimating the healing process.

Some blood cell-derived indexes, including SII, NLR, PLR, and LMR, have been proposed as biomarkers for various inflammatory and non-inflammatory diseases. As a result, we felt compelled to investigate the blood cell-derived indexes, considering the severity of inflammation, duration of the disease, and treatment in patients with SAT. Although there are many studies on various hemogram-related ratios of subacute thyroiditis in the literature, the number of the studies on subacute thyroiditis and SII is limited.15,16 In these studies, as in our study, SII level has elevated significantly in the patient group with SAT when compared to the control group. However, the current study differs from the other studies in question owing to being a prospective observational study. Apart from this, whether blood cell-based inflammatory markers, particularly SII, are associated with recovery time is one of the most significant research subjects, considering the scope of our study. We found that SII may have prognostic value in predicting the healing process as well as its diagnostic role.

ESR, CRP, SII, PLR, and NLR levels in this study were found to be higher in the patient group, whereas the LMR level was found to be lower. SII and other inflammation markers such as CLR and SLR showed a statistically significant positive correlation. All these parameters might be used to assist acute-phase reactants in detecting inflammatory burden at the time of diagnosis. In the study of Takaldiran et al, NLR and PLR levels were found to be higher in patients with SAT than in the control group, similar to our study.17 We also revealed that patients with higher SII levels had a significantly longer recovery period. We know that the types of treatment have a strong confounding effect on the correlation between SII and recovery time. For this reason, we also studied on the correlation between the recovery time and SII based on the treatment modalities performed. We determined that SII levels affected the recovery time with a strong positive correlation in the patients receiving MPS, not NSAID. Not surprisingly, SII levels were found to be higher in patients receiving MPS due to the presence of milder clinical conditions in patients treated with NSAIDs.

In clinical practice, it is important to decide the most effective and appropriate treatment in the acute phase of the disease through the combination of all parameters such as medical history, clinical, laboratory, and imaging findings, and the severity of the disease, which accurately assess the inflammatory burden of the disease in patients with SAT suffering from severe pain and hyperthyroidism symptoms in order not to cause loss of time.

Thyroid inflammation and hyperthyroidism are usually transient, lasting two to eight weeks. Euthyroidism, hypothyroidism, and finally restoration of normal thyroid functions are experienced following hyperthyroidism. Some patients may skip the hyperthyroid phase entirely and proceed directly from the hypothyroid phase to the recovery phase, which is diagnosed clinically in general. However, 5% to 15% of patients progress to persistent thypothyroidism, which requires levothyroxine treatment.18,19 As mentioned above, hypothyroidism is generally transient, but it may nevertheless be permanent. In our study, hypothyroidism developed in 17% of the patients, pursuant to the study results in the literature. However, no correlation was found between the development of hypothyroidism and hematological parameters. The relatively short follow-up period of only 612 months, which is critical for progression to relapse or hypothyroidism in our study, may have affected this correlation.

In our study, patients receiving MPS had a higher SAT recurrence rate (21%), and the total recurrence rate was 11% consistent with the literature.20 In addition, TSH levels at the time of diagnosis were higher in the recurrence group, while TSH levels were lower in the non-recurrence group in accordance with the literature.21,22 Since the recurrence rate of patients with clinically severe hyperthyroidism is lower, the duration of the treatment administered may be shorter, which reduces the possibility of side effects when compared to a longer treatment period.

SII is a widely available, low-cost, universal, non-invasive, and easy-to-reproduce method for detecting inflammation on SAT. As a result, predicting the prognosis and the duration of the disease in the SAT acute phase could provide benefits in the follow-up process, as well as in the selection of aggressive anti-inflammatory treatment. Although SAT is a benign, self-limiting disease, the severe inflammatory burden of the disease in the acute phase may be exhausting for both patients and physicians. According to the results of our study, estimating the duration of the recovery period by considering the level of SII at the time of the diagnosis has importance. As a high SII level indicates a longer recovery period, deciding whether an aggressive treatment with a higher anti-inflammatory effect as the initial treatment would prevent loss of time. On the other hand, a low SII level indicates a shorter recovery period, which means patients may complete the treatment process without suffering any complications and side effects of a more aggressive treatment. Additionally, we found that higher pre-treatment TSH and ESR values may be a risk factor for recurrence. In clinical practice, this result may help the clinician choose an appropriate treatment without increasing recurrence risk, which is already high in the case of high TSH and ESR levels. In addition, shortening the duration of treatment may be considered in patients at low risk of recurrence.

With all these clinical data, multicenter studies involving a large number of patients and years of follow-up are required for SAT.

ESR and CRP levels play a crucial role in the diagnosis of SAT; however, SII level may also be a parameter in order to give clinicians an idea not only on the diagnosis of the disease but also on its prognosis. As a practical biomarker, SII level may be a new diagnostic and prognostic tool for SAT. According to our point of view, more comprehensive studies with a long follow-up period and a large number of patients need to be conducted to contribute to the research on SAT in the literature.

SAT, Subacute thyroiditis; SII, Systemic Immune-Inflammation Index; TSH, thyroid stimulating hormone; NSAIDs, non-steroidal anti-inflammatory agents; MPS, methylprednisolone; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; PLR, platelet-to-lymphocyte ratio; LMR, lymphocyte-to-monocyte ratio; NLR, neutrophil-to-lymphocyte ratio; SLR, sedimentation-to-lymphocyte ratio; CLR, CRP-to-lymphocyte ratio.

The datasets analysed during the current study are available from the corresponding author on reasonable request.

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Erzurum Training and Research Hospital Ethics Committee (Decision KAEK 2022/07-72 Date: 06.06.2022). Written informed consent was obtained from all participants.

We would like to thank the Society of Endocrinology and Metabolism of Trkiye for their valuable contributions to the research process by providing data and to the translation process.

There is no specific funding related to this research.

The authors report no conflicts of interest.

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2. Grges J, Ulrich J, Keck C, Mller-Wieland D, Diederich S, Janssen OE. Long-term outcome of subacute thyroiditis. Exp Clin Endocrinol Diabetes. 2020;128:703708. doi:10.1055/a-0998-8035

3. Stasiak M, Lewiski A. New aspects in the pathogenesis and management of subacute thyroiditis. Rev Endocr Metab Disord. 2021;22:10271039. doi:10.1007/s11154-021-09648-y

4. Intenzo CM, Park CH, Kim SM, Capuzzi DM, Cohen SN, Green P. Clinical, laboratory, and scintigraphic manifestations of subacute and chronic thyroiditis. Clin Nucl Med. 1993;18(4):302306. doi:10.1097/00003072-199304000-00007

5. Vural , Paksoy N, Gk ND, Yazal K. Subacute granulomatous (De Quervains) thyroiditis: fine-needle aspiration cytology and ultrasonographic characteristics of 21 cases. Cytojournal. 2015;12:9. doi:10.4103/1742-6413.157479

6. Fois AG, Paliogiannis P, Scano V, et al. The Systemic Inflammation Index on admission predicts in-hospital mortality in COVID-19 patients. Molecules. 2020;25:5725. doi:10.3390/molecules25235725

7. Calapkulu M, Sencar ME, Sakiz D, et al. The prognostic and diagnostic use of hematological parameters in subacute thyroiditis patients. Endocrine. 2020;68:138143. doi:10.1007/s12020-019-02163-w

8. Wang J, Arase H. Regulation of immune responses by neutrophils. Ann N Y Acad Sci. 2014;1319:6681. doi:10.1111/nyas.12445

9. Hu B, Yang XR, Xu Y, et al. Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res. 2014;20(23):62126222. doi:10.1158/1078-0432.CCR-14-0442

10. Fest J, Ruiter R, Ikram MA, Voortman T, Van Eijck CHJ, Stricker BH. Reference values for white blood-cell-based inflammatory markers in the Rotterdam Study: a population-based prospective cohort study. Sci Rep. 2018;8(1):10566. doi:10.1038/s41598-018-28646-w

11. Yang R, Chang Q, Meng X, Gao N, Wang W. Prognostic value of Systemic immune-inflammation index in cancer: a meta-analysis. J Cancer. 2018;9(18):32953302. doi:10.7150/jca.25691

12. Zhong JH, Huang DH, Chen ZY. Prognostic role of systemic immune-inflammation index in solid tumors: a systematic review and meta-analysis. Oncotarget. 2017;8(43):7538175388. doi:10.18632/oncotarget.18856

13. Alende-Castro V, Alonso-Sampedro M, Vazquez-Temprano N, et al. Factors influencing erythrocyte sedimentation rate in adults: new evidence for an old test. Medicine. 2019;98(34):e16816. doi:10.1097/MD.0000000000016816

14. Feldman M, Aziz B, Kang GN, Opondo MA, Belz RK, Sellers C. C-reactive protein and erythrocyte sedimentation rate discordance: frequency and causes in adults. Transl Res. 2013;161(1):3743. doi:10.1016/j.trsl.2012.07.006

15. Keskin , Dileki EN, ZA, Cengiz D, Duran C. Can the systemic immune-inflammation index be used as a novel diagnostic tool in the diagnosis of subacute thyroiditis? Biomark Med. 2022;16(10):791797. doi:10.2217/bmm-2022-0095

16. He P, Yang H, Lai Q, et al. The diagnostic value of blood cell-derived indexes in subacute thyroiditis patients with thyrotoxicosis: a retrospective study. Ann Transl Med. 2022;10(6):322. doi:10.21037/atm-22-719

17. Takaldiran I, Omma T, nder E, et al. Neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and platelet-to-lymphocyte ratio in different etiological causes of thyrotoxicosis. Turk J Med Sci. 2019;49(6):16871692. doi:10.3906/sag-1901-116

18. Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med. 2003;348(26):26462655. doi:10.1056/NEJMra021194

19. Ross DS, Burch HB, Cooper DS, et al. American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26(10):13431421. doi:10.1089/thy.2016.0229

20. Sencar ME, Calapkulu M, Sakiz D, et al. An evaluation of the results of the steroid and non-steroidal anti-inflammatory drug treatments in subacute thyroiditis in relation to persistent hypothyroidism and recurrence. Sci Rep. 2019;9(1):16899. doi:10.1038/s41598-019-53475-w

21. Stasiak M, Tymoniuk B, Stasiak B, Lewiski A. The risk of recurrence of subacute thyroiditis is HLA-dependent. Int J Mol Sci. 2019;20(5):1089. doi:10.3390/ijms20051089

22. Bahadir T, Yilmaz M, Kilikan E. Factors affecting recurrence in subacute granulomatous thyroiditis. Arch Endocrinol Metab. 2022;66(3):286294. doi:10.20945/2359-3997000000473

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Systemic Immune Inflammation Index Predictor for Thyroiditis | IJGM - Dove Medical Press

Endocrinology

The impact of SARS-CoV-2 infection in pregnancy on infant growth – News-Medical.Net

A recently accepted article manuscript published in the Journal of Clinical Endocrinology and Metabolism discussed recent findings on the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy on infant growth.

Study:Whats past is prologue: growth in infants born from pregnancies complicated by SARS-CoV-2 infection. Image Credit:MIAStudio/Shutterstock.com

SARS-CoV-2 infection in pregnancy raises concerns about the potential risk of transmission to the fetus and the adverse uterine environment for the growing fetus.

The pressing need for research in this domain was recognized, leading to longitudinal studies on the impact of coronavirus disease 2019 (COVID-19) during pregnancy and the development of biorepositories.

COVID-19 can cause excess complications in pregnancy, such as prematurity, preeclampsia, gestational hypertension, and a proinflammatory systemic milieu, that may impact lifelong infant health.

A recent study compared longitudinal trajectories of length, weight, and body mass index (BMI) between infants with and without in-utero exposure to SARS-CoV-2.

The investigators excluded mothers vaccinated during the study period to decrease heterogeneity. The study found that SARS-CoV-2-exposed infants had lower BMI at birth, even when adjusted for gestational age and relevant covariates than those without exposure.

Notably, BMI increased rapidly in exposed infants in the first year of life after accounting for factors influencing BMI.

Also, this postnatal increase in BMI was the steepest in those born to those with severe COVID-19. Statistical analyses revealed that low birth weight mediated most effects of COVID-19 on postnatal BMI increase. Although minor changes in length were noticeable, they were not statistically significant.

Measuring infant length is challenging and could be more error-prone in clinical and research settings. Therefore, research data collection and larger samples may better appreciate the impact of exposure to SARS-CoV-2 on infant growth.

A multinational study on neonates with and without in-utero exposure to COVID-19 found that newborns were small. With weight, head circumference, and length being adversely impacted.

Previously, the authors of the present study observed that infants born with lower BMI had a rapid postnatal increase and noted that exposure to poverty or tobacco was associated with the postnatal BMI catch-up. Further, epidemiologic studies report associations between low birth weight and later catch-up with excess cardiometabolic risk during adulthood.

However, they do not establish a causal relationship between rapid gain in infant weight and adverse outcomes later in life. Socioeconomic disparities contributing to adverse health throughout the lifecycle may contribute to this pattern. Thus understanding the long-term risks associated with the rapid weight gain of infants exposed to COVID-19 in-utero is yet to be determined.

Thus, more research is necessary to understand how long the effects of antenatal COVID-19 persist in life after birth. Additionally, identifying protective factors might result in strategies to enhance preventive care in infants after in-utero SARS-CoV-2 exposure.

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Tarun is a writer based in Hyderabad, India. He has a Masters degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.

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Endocrinology

INDIA NEEDS A SPORTING CULTURE TO EXCEL IN THE WORLD … – Face2News

TWO DAYS CONFERENCE ON ENDOCRINOLOGY CONCLUDES.

Face2News/Chandigarh:

The two-days medical conference named EPIC (Empower Physicians with International Practices in advanced Diabetes Care), concluded here yesterday with a motivational keynote by the Padma Bhushan Olympian Abhinav Bindra.

Abhinav shared his lifes journey and how the sports changed his outlook towards life with various facets of life and character that helped him develop better self-respect, self-discipline, and self-confidence, and more importantly overcome the fear of failure.

One learns to listen to ones coach and other experts and self-analyse ones strengths and weaknesses, and hone the ability to stay in the moment, focussed and determined, through regular practice, he said, which everyone should try to be the best and get better than yesterday.

The conference concluded with a session on Work-Life balance by ex-IAS, author, and TEDx speaker Vivek Atray, who touched upon physical and mental fitness by advising patients to follow creative pursuits and manage their anger and stress through regular meditation, essential to managing the lifestyle disease like diabetes and obesity.

Abhinav responded to the doctors queries on stress, and anxiousness, he said that all conflicts emerge within and it is only through the practice of staying focussed on the moment to accomplish what one wants to do can make a difference.

When asked about the absence of more sportspeople winning medals for the country, Abhinav said that we need to develop a culture of sports with everyone happily participating in games joyfully, and celebrating it, which would encourage more youth to excel for better performance.

Abhinav Bindra along with EPICs organizing chairman Dr. Sanjay Kalra and secretary Dr. Sachin Mittal conferred Lifetime Achievement Award on two stalwarts in the field of endocrinology, Dr. B. S. Bhatia, Prof. Sarita Bajaj, for their contribution in the field.

Earlier the medical sessions covered various aspects of diabetic patients, wherein the cardiologists Dr. HK Bali, Dr Puneet Verma, Dr Rajneesh Mittal, Dr. Soumik Goswami, Dr. Anil Dhall, Dr. Neeraj Bhalla and Dr. Dilip Bhalla, underlined the need for early detection, prevention and treatment of cardio-renal damage to

Dr. Akshata Desai, Dr. Gurpreet Singh, Dr Mani Kant Singla, Dr Savita Kapila, Dr JK Mokta, Do Soham Mukherjee looked at the practical challenges and solutions in the use of insulin for diabetic patients.

The conference concluded with a session on Work-Life balance by ex-IAS, author, and TEDx speaker Vivek Atray, who touched upon physical and mental fitness by advising patients to follow creative pursuits and manage their anger and stress through regular meditation, essential to managing the lifestyle disease like diabetes and obesity.

Dr. Sachin Mittal, organising secretary, said that sensitization of general practitioners towards newer developments in endocrinology was essential and also how different organs affected by diabetes need to be taken care of at an early stage.

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INDIA NEEDS A SPORTING CULTURE TO EXCEL IN THE WORLD ... - Face2News

Endocrinology

Research suggests brain receptor linked to PCOS symptoms – Mirage News

Polycystic ovarian syndrome, or PCOS, can cause a range of symptoms, including disrupted menstrual cycles, abdominal obesity, cardiovascular disease, and type 2 diabetes. Its also one of the biggest causes of infertility in fact, many people dont discover they have the condition until they try to become pregnant.

One of the hallmarks of PCOS are elevated levels of hormones produced by the ovaries called androgens. Androgens play important roles in puberty and reproduction in people with ovaries and people with testes.

Researchers are trying to understand why PCOS develops and how androgens lead to negative symptoms. A recent study led by Alexandra Cara, Ph.D., a former graduate student in the U-M Medical Schools Department of Molecular and Integrative Physiology, used mouse models to take a closer look at hormonal receptors.

If you expose mice to androgens during two critical windows, before birth or around puberty, they will go on to develop different symptoms of PCOS, said Cara, now a postdoctoral research fellow at the University of California, Los Angeles. Some scientists believe prenatal exposure to androgens or endocrine-disrupting chemicals may lead to PCOS in humans as well.

The study, published in the journal Endocrinology, builds on earlier work in which researchers deleted the androgen receptors (which as their name suggests bind to androgens) in mice. They then exposed the animals to excess androgens before they were born. Without androgen receptors, the mice were protected from developing some symptoms of PCOS.

But, explains Cara, androgen receptors are located throughout the body, including the brain, and deleting them all still left the open question of which receptors were implicated for PCOS development.

Cara hypothesized that another type of receptor called the leptin receptor, studied extensively by her principal investigator Carol Elias, Ph.D., may be involved. Previous work found androgen receptors are highly expressed in certain populations of leptin receptor-expressing neurons in the hypothalamus part of the brain that controls the release of hormones. Leptin, a hormone produced by fat tissue, is involved in the regulation of appetite and metabolism.

We know that a subpopulation of people with PCOS are more likely to have diabetes and visceral obesity. We thought leptin could be a good link between metabolism and reproduction and might be influenced by androgen receptor-mediated androgen signaling, she said.

To test this hypothesis, the team exposed mice that had androgen receptors deleted from leptin receptor neurons to excess androgens prenatally. These mice had improvement in some PCOS symptoms including regulation of their estrous cycles (analogous to a menstrual cycle in humans.)

Cara hopes follow up studies will explore androgen exposure around puberty, as this type of model tends to mimic the weight gain found in some people with PCOS.

I hope these mouse studies can find better therapeutic targets for people with PCOS, Cara said. The first intervention offered is lifestyle modification, like diet and exercise, but as anyone with the condition would tell you, that doesnt help everything.

Even with body weight regulation and restoration of menstrual cycles, people can still struggle with getting pregnant. And while anti-androgen drugs can block the hormones in the body, you cant take them when trying to conceive, she noted.

Its hard to have a perfect model of PCOS, but this is the closest weve gotten so far, said Elias. Once we have a good idea what is causing PCOS and how it develops, things get easier to target.

Paper cited: Deletion of Androgen Receptor in LepRb Cells Improves Estrous Cycles in Prenatally Androgenized Mice, Endocrinology. DOI: 10.1210/endocr/bqad015

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Research suggests brain receptor linked to PCOS symptoms - Mirage News

Immunology

Genmab and argenx Enter Partnership to Advance Antibody Therapies in Immunology and Oncology – GlobeNewswire

Media Release

COPENHAGEN, Denmark; April 17, 2023

GenmabA/S(Nasdaq:GMAB) andargenx(Euronext & Nasdaq:ARGX) announced today that Genmabandargenxhave entered into a collaboration agreement to jointly discover, develop and commercialize novel therapeutic antibodies with applications in immunology, as well as in oncology therapeutic areas.Themultiyear collaboration will leverage the antibody engineering expertise and knowledge of disease biology of both companies to accelerate the identification and development of novel antibody therapeutic candidates with a goal to address unmet patient needs in immunology and cancer.

Genmabis entering the therapeutic area of immunologyand inflammationas asteppingstoneto achievingitsvision that by 2030, our knock-your-socks-offKYSOantibody medicines will be transforming the lives of people with cancer and other serious diseases, said Jan van de Winkel, Ph.D., Chief ExecutiveOfficer,Genmab. By partnering with argenx, we will be able to combine our deep knowledge of the biology and therapeutic power of antibodies and have an opportunity to address patients needs in oncology as well as in immunology and inflammation.

Our core mission is to innovate on behalf of patients by translating immunology breakthroughs into novel pipeline candidates. We do this through a model of co-creation which has led to eight molecules demonstrating human proof-of-concept in our pipeline, said Tim Van Hauwermeiren, Chief Executive Officer, argenx. Through our collaboration with Genmab, we are bringing together our combined antibody discovery, development and commercialization expertise to unlock insights on the disease pathways that we will address. This allows us to broaden our capabilities and maximize the opportunity to generate novel therapeutic antibodies within autoimmunity or cancer.

Collaboration DetailsAs per the agreement,argenxandGenmabwill each have access to the suites of proprietary antibody technologies of both companies to advance the identification of lead antibody candidates against differentiated disease targets. Under the terms of the agreement, argenx and Genmab will jointly discover, develop and commercialize products emerging from the collaboration while equally sharing costs as well as any potential future profits. The collaboration will initially focus on two differentiated targets, including one within immunology and one within cancer, with the potential to expand to more.

About Genmab Genmab is an international biotechnology company with a core purpose guiding its unstoppable team to strive towards improving the lives of patients through innovative and differentiated antibody therapeutics. For more than 20 years, its passionate, innovative and collaborative team has invented next-generation antibody technology platforms and leveraged translational research and data sciences, which has resulted in a proprietary pipeline including bispecific T-cell engagers, next-generation immune checkpoint modulators, effector function enhanced antibodies and antibody-drug conjugates. To help develop and deliver novel antibody therapies to patients, Genmab has formed 20+ strategic partnerships with biotechnology and pharmaceutical companies. By 2030, Genmabs vision is to transform the lives of people with cancer and other serious diseases with Knock-Your-Socks-Off (KYSO) antibody medicines.

Established in 1999, Genmab is headquartered in Copenhagen, Denmark with locations in Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo, Japan. For more information, please visit Genmab.com and follow us on Twitter.com/Genmab.

About argenxargenx is a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases. Partnering with leading academic researchers through its Immunology Innovation Program (IIP), argenx aims to translate immunology breakthroughs into a world-class portfolio of novel antibody-based medicines. argenx developed and is commercializing the first-and- only approved neonatal Fc receptor (FcRn) blocker in the U.S., Japan, and the EU. The Company is evaluating efgartigimod in multiple serious autoimmune diseases and advancing several earlier stage experimental medicines within its therapeutic franchises. For more information, visitwww.argenx.comand follow us onLinkedIn,Twitter,andInstagram.

Genmab Contacts

Media

Jyoti Sharma, Director, Communications T: +1 609 480 9844; E: jysh@genmab.com

Investor Relations

Andrew Carlsen, Vice President, Head of Investor RelationsT: +45 3377 9558; E: acn@genmab.com

argenx Contacts

Media

Erin Murphyemurphy@argenx.com

Investors

Beth DelGiaccobdelgiacco@argenx.com

Genmab Forward-looking Statements This Media Release contains forward looking statements. The words believe, expect, anticipate, intend and plan and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with pre-clinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmabs most recent financial reports, which are available on http://www.genmab.com and the risk factors included in Genmabs most recent Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at http://www.sec.gov. Genmab does not undertake any obligation to update or revise forward looking statements in this Media Release nor to confirm such statements to reflect subsequent events or circumstances after the date made or in relation to actual results, unless required by law.

Genmab A/S and/or its subsidiaries own the following trademarks: Genmab; the Y-shaped Genmab logo; Genmab in combination with the Y-shaped Genmab logo; HuMax; DuoBody; DuoBody in combination with the DuoBody logo; HexaBody; HexaBody in combination with the HexaBody logo; DuoHexaBody and HexElect.

argenx Forward-looking StatementsThe contents of this announcement include statements that are, or may be deemed to be, forward- looking statements. These forward-looking statements can be identified by the use of forward- looking terminology, including the terms believes, hope, estimates, anticipates, expects, intends, may, will, or should and include statements argenx makes regarding the impact of the transitionof the chief operatingofficer; its launchstrategytomake VYVGARTavailable inthe EU, China, Canadaandselect otherregions;the VYVGARTmulti-dimensional expansionstrategy; its expansionthroughpotential regulatoryapprovals andlaunches and the planned launchof SC efgartigimod, ifapproved;the timingofdata readoutsandnew clinical efficacydata; theregulatory reviews andregulatoryapproval timinginthe United States,EU andJapan forSCefgartigimod forthe treatment ofgMG andthe long-term safety andtolerability ofSC efgartigimod; thetherapeutic potentialof itsproduct candidates; the intendedresults of itsstrategy andits collaborationpartners,advancement of, andanticipated clinical developmentandregulatorymilestonesandplans, including the timing of planned clinical trials; and the design of future clinical trials and the timing and outcome of regulatory filings and regulatory approvals. By their nature, forward-looking statements involverisksanduncertainties, andreadersarecautionedthatanysuchforward-lookingstatementsarenotguaranteesoffutureperformance.argenxsactualresultsmaydiffermateriallyfrom thosepredictedbytheforward-lookingstatementsasaresultofvariousimportantfactors, includingtheeffectsoftheCOVID-19pandemic,inflationanddeflationandthecorrespondingfluctuationsininterestrates;regionalinstabilityandconflicts,suchastheconflictbetweenRussiaandUkraine,argenxsexpectationsregardingtheinherentuncertainties associatedwithcompetitivedevelopments,preclinicalandclinicaltrialandproductdevelopmentactivitiesandregulatoryapprovalrequirements;argenxsrelianceoncollaborationswiththirdparties;estimatingthecommercialpotentialof argenxsproductcandidates;argenxsabilitytoobtainandmaintainprotectionofintellectualpropertyfor itstechnologiesanddrugs; argenxslimitedoperatinghistory;andargenxsabilitytoobtainadditionalfundingforoperationsandtocompletethedevelopmentandcommercializationofitsproductcandidates.Afurtherlistanddescriptionofthese risks, uncertainties andotherrisks canbe foundin argenxsU.S. Securities andExchange Commission(SEC)filings andreports, includingin argenxsmostrecent annual report onForm20-Ffiled with the SEC as well assubsequent filingsandreports filed byargenxwith theSEC.Giventhese uncertainties,the readeris advised not toplace any undue reliance onsuchforward-lookingstatements.Theseforward-lookingstatements speak onlyas ofthe dateof publicationof this document. argenx undertakesnoobligationto publicly update or revisethe informationinthis pressrelease, including any forward-looking statements, except as may be required by law.

Media Releaseno.04CVR no. 2102 3884LEI Code 529900MTJPDPE4MHJ122

Genmab A/SKalvebod Brygge 431560 Copenhagen VDenmark

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Genmab and argenx Enter Partnership to Advance Antibody Therapies in Immunology and Oncology - GlobeNewswire

Immunology

Mercks $10.8 billion takeover of Prometheus gives it a foothold in immunology – MarketWatch

Merck & Co.s $10.8 billion acquisition of Prometheus Biosciences Inc., which it announced Sunday, is a strategic positive that will help the drug company diversify its portfolio and reduce the risk of an overreliance on its cancer drug Keytruda, analysts said Monday.

San Diego, Calif.-based Prometheus RXDX is a clinical-stage biotechnology company focusing on autoimmune treatments, such as PRA023, a treatment under development for illnesses such as ulcerative colitis and Crohns disease.

This transaction adds further diversity to our overall portfolio and is an important building block in strengthening the sustainable innovation engine that will drive our long-term success, Merck Chief Executive Rob Davis told analysts on a call to discuss the deal, according to a FactSet transcript.

BofA analysts said diversity is a key goal for Merck, given that Keytruda is expected to account for more than 45% of total revenue by 2025.

Whilewe wouldnt expect todays proposed transaction to meaningfully move Mercks shareson Monday given its relative size, we see the deal as a strategic positive and another step in the right direction to diversify Keytruda concentration risk, analysts led by Geoff Meacham wrote in a note to clients.

Also see:Moderna, Merck combo cancer-vaccine treatment shows significant promise

BofA has a buy rating on Merck MRK

Prometheus had a market cap of about $5.42 billion as of Fridays close. Its stock is up 3.7% year to date but has skyrocketed 225% over the past 12 months, with much of the gains coming afterPRA023 advanced to Phase 3 clinical trialsin December. The news of the Merck deal with its 70% premium sent the stock up 69% on Monday.

PRA023 is an antibody that binds TL1A,a target associated with both intestinal inflammation and fibrosis, said the BofA analysts. Phase 2 studies have demonstrated the best-in-class potential for the drug, which is a potential disrupter in the inflammatory and immunology space and has a pipeline that stretches beyond inflammatory bowel disease, or IBD, they wrote.

Read now: Merck and Eisai report disappointing results from trials of combination treatment for melanoma and colorectal cancer

IBD is the umbrella term used to describe diseases including Crohns and ulcerative colitis, both of which cause chronic inflammation of the gastrointestinal tract, leading to diarrhea, rectal bleeding, abdominal pain, fatigue and weight loss.

Prometheus has a roughly $5 billion potential by 2030, the analysts said, although they noted that with Phase 3 studies to be launched this year, there is still a lot of wood to chop before commercialization, which is expected by 2026.

Stifel analysts led by Annabel Samimy said: We see Merck as having captured a plum asset with potentially little competition (due to exposure overlap amongst most other large pharma) adding a strong franchise in immune-mediated/fibrotic conditions to its current focus areas in oncology, infectious disease, and cardio-metabolic disorders.

Stifel is not anticipating any major antitrust issues to arise, given that the deal is Mercks first foray into the immune-mediated space, while other big drug companies, including Bristol Myers Squibb Co. BMY , AbbVie Inc. ABBV , Pfizer Inc. PFE and Johnson & Johnson

See now: Moderna is developing a vaccine against the tick-borne Lyme disease, in a first for the company

Guggenheim analysts led by Yatin Suneja said the deal is the cherry on top of its Best Idea for 2023, which was to buy Prometheus stock.

PRA023 is a potential game changer that could break through the efficacy ceiling that has plagued the [IBD] space for years, they wrote. The deal is not just good for Merck, either Prometheus gets the global infrastructure and resources of a big pharma company to help push through Phase 3 trials.

Given the big opportunity for 2023 in IBD, we see this valuation as reasonable and dont expect any competing offers, they wrote.

Guggenheim has a buy rating on Merck.

Mercks stock was down 0.5% Monday but has gained 3.4% in the year to date, while the S&P 500 SPX has gained 7.8%.

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Mercks $10.8 billion takeover of Prometheus gives it a foothold in immunology - MarketWatch

Immunology

Merck to buy Prometheus Biosciences for US$10.8b – theSundaily

Merck will pay US$200 per share for the California-based biotechnology company that specialises in treatments for autoimmune diseases. That represents a 75% premium to the US$114.01 closing price for Prometheus shares on Friday.

This is allowing us to move into immunology in a strong way and will allow us sustainable growth, we think, well into the 2030s given the long patent life, Merck chief executive Robert Davis said in an interview.

Davis said the Prometheus drug, PRA023, being developed to treat ulcerative colitis, Crohns disease, and other autoimmune conditions, could be a multibillion-dollar seller for Merck. He said the recent release of encouraging Phase II clinical trial results drove Merck to pounce.

Weve been watching their clinical development programme for a while, Davis said.

If the deal closes in the third quarter of this year as hoped, Merck could launch a late-stage ulcerative colitis study of the drug in the fourth quarter or first quarter of 2024, Davis said.

Merck has been looking for deals to protect itself from eventual revenue loss as patents on its blockbuster cancer immunotherapy Keytruda begin to expire toward the end of the decade. The company reported nearly US$21 billion in Keytruda sales last year.

Davis said revenue from the Prometheus acquisition could start to roll in around the time Keytruda patents could potentially expire.

Davis compared the deal to one he struck in 2021 for Acceleron, which allowed Merck to quickly build out its pipeline of cardiovascular drugs.

I believe now we have a very strong portfolio in the cardiometabolic space. We see this acquisition of Prometheus building out a similar portfolio in the immunology space, Davis said, adding that Merck brings scale, global reach and significant capital to deploy.

Last summer, Merck was reportedly in talks to buy cancer focused biotech Seagen Inc, but rival Pfizer Inc ended up striking a US$43 billion deal for Seagen last month.

Davis said Merck would continue to be opportunistic on acquisitions, but is agnostic about size.

We look where we see the most compelling science, and where that science aligns with value we move, he said, noting that the company is not interested in large transformative or cost-synergy driven deals.

Mercks talks with Prometheus were first reported by The Wall Street Journal.

The company in February forecast 2023 earnings below Wall Street estimates and a steep decline in sales of its Covid-19 antiviral treatment. - Reuters

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Merck to buy Prometheus Biosciences for US$10.8b - theSundaily

Immunology

Nektar Therapeutics Announces Strategic Reprioritization and Cost Restructuring Plan – Yahoo Finance

-- Pipeline focus will prioritize programs in immunology, including REZPEG and several immunology research programs --

-- Development of NKTR-255 in diffuse large B-cell lymphoma and bladder cancer to continue as strategic partnering options are pursued --

-- Cost restructuring plan reduces San Francisco-based workforce by approximately 60% and extends cash runway into the middle of 2026 --

-- Company to announce financial results for the first quarter of 2023 after close of U.S.-based financial markets on May 9, 2023 --

SAN FRANCISCO, April 17, 2023 /PRNewswire/ --Nektar Therapeutics (Nasdaq: NKTR) today announced a strategic reprioritization and cost restructuring plan that includes a new pipeline focus on immunology, as well as several cost reduction initiatives, which the company expects will significantly reduce future operating expenses and extend its cash runway into the middle of 2026.

(PRNewsfoto/Nektar Therapeutics)

Key elements of the new plan include:

Prioritize REZPEG development: Nektar intends to work with Eli Lilly to ensure the continuation of REZPEG development whether it is under the existing Eli Lilly agreement or Nektar regains the rights to REZPEG. The Phase 1b data for REZPEG in atopic dermatitis previously presented at the EADV meeting in September 2022 showed that a dose-dependent improvement was observed in key efficacy measures of mean change in EASI, EASI-75, vIGA-AD scores, and Itch NRS 4-point improvement ratesover placebo with 12 weeks of treatment. These improvements were observed for an additional 36 weeks following the 12-week treatment period. These proof-of-concept data show REZPEG's ability to stimulate Tregs to target an immune system imbalance resulting in an improvement of disease activity in patients. The Phase 1b data were recently highlighted in a talk by Eric Lawrence Simpson, MD, FAAD at the 2023 American Academy of Dermatology (AAD) Annual Meeting on March 17, 2023 in the scientific session covering atopic dermatitis, as a potential future remittive therapy.

Continue development of lead oncology asset, NKTR-255, while seeking a strategic development partner: As part of the strategic reprioritization, Nektar will continue its Phase 2 study of NKTR-255 in combination with cell therapies and the Phase 2 JAVELIN Bladder Medley Study with partner Merck KGaA while it explores strategic partnership options for NKTR-255. NKTR-255 is an investigational IL-15 receptor agonist designed to boost antitumor immunity by increasing the proliferation and survival of natural killer and memory CD8+ T cells and may have broad potential applicability across oncology indications.

Continue core research programs in immunology: Nektar will continue to advance two preclinical pipeline candidates in auto-immune diseases including a new PEG-Colony Stimulating Factor (CSF1) program and a separate TNFR2 agonist antibody being developed in collaboration with Biolojic Design. The company plans to file an IND for at least one of these programs in 2024.

Implement a cost restructuring plan: As part of the strategic reprioritization, Nektar also plans to reduce its San Francisco-based workforce by approximately 60%. Once the cost restructuring plan has been fully completed, the company is expected to have approximately 55 employees based in San Francisco. The company anticipates that its Huntsville manufacturing facility, which supports several large pharmaceutical partners, will continue to operate with its current staff. The restructuring also includes actions to reduce additional operating costs and is expected to be substantially completed by June 2023.

Story continues

"Following a comprehensive review of our portfolio, we have made the decision to prioritize the advancement of our immunology programs," said Howard W. Robin, President and CEO of Nektar. "We intend to work with Eli Lilly either to continue REZPEG's development in the clinic under our existing agreement or to regain the rights to REZPEG for Nektar. We believe the strong data generated for this asset demonstrates its potential as a remittive therapy in atopic dermatitis and sets the stage to move quickly into a Phase 2b study. REZPEG would be positioned as a novel potential therapeutic in a significant, growing biologic treatment landscape."

"The strategic initiative we announced today is intended to further streamline our operations and to extend considerably our cash runway into the middle of 2026," continued Robin. "Although the actions we are taking today are difficult, we are incredibly grateful for the contributions of the employees departing Nektar."

Nektar had cash, cash equivalents, and marketable securities of approximately $456 million as of March 31, 2023. These significant reductions in the company's operating expenses, including personnel-related costs and external expenses, are expected to extend the company's cash runway into the middle of 2026. Projected annual savings from the headcount reduction will be fully realized in 2024 and represent an annual savings of approximately $30 million. Nektar expects non-recurring cash payments of approximately $8 million, primarily in the second quarter of 2023 associated principally with the workforce reduction.

Executive Management Changes

As part of this initiative, Nektar also announced several changes to its executive team:

Dr.Brian Kotzin, Nektar's Chief Medical Officer, will be stepping down from his full-time role but will continue to serve in an ongoing role as a strategic advisor to the company. Dr. Mary Tagliaferri, current Chief Development Officer, will assume the role of Chief Medical Officer.

Jillian Thomsen will be stepping down from her role as Chief Financial Officer (CFO) and will depart the company in June following a transition period. The company has appointed Sandra Gardiner to the role of acting CFO. Sandra is a skilled business and finance executive with over 30 years of financial and accounting experience. She is a partner at FLG Partners, a leading CFO services firm in Silicon Valley.

Kevin Brodbeck, Nektar's SVP of Technical Operations, will depart the company in June following a transition period. Ken Franke, current VP of Biologics Development & Manufacturing will assume Kevin's responsibilities.

The company thanks its departing executives for their contributions to Nektar.

Conference Call Details to Announce First Quarter 2023 Financial Results:

Nektar will announce its financial results for the first quarter 2023 on Tuesday, May 9, 2023, after the close of U.S.-based financial markets. Howard W. Robin, President and Chief Executive Officer, will host a conference call to review the results beginning at 5:00 p.m. Eastern Time/2:00 p.m. Pacific Time.

The press release and live audio-only webcast of the conference call can be accessed through a link that is posted on the Home Page and Investors section of the Nektar website: http://ir.nektar.com/. The web broadcast of the conference call will be available for replay through June 4, 2023.

To access the conference call, please pre-register at Nektar Earnings Call Registration. All registrants will receive dial-in information and a PIN allowing them to access the live call.

About Nektar Therapeutics

Nektar Therapeutics is a biopharmaceutical company with a robust, wholly owned R&D pipeline of investigational medicines in immunology and oncology as well as a portfolio of approved partnered medicines. Nektar is headquartered in San Francisco, California, with additional manufacturing operations in Huntsville, Alabama. Further information about the company and its drug development programs and capabilities may be found online at http://www.nektar.com.

About Rezpegaldesleukin (REZPEG)

Autoimmune and inflammatory diseases cause the immune system to mistakenly attack and damage healthy cells in a person's body. A failure of the body's self-tolerance mechanisms enables the formation of the pathogenic T lymphocytes that conduct this attack. REZPEG is an investigational, potential first-in-class T regulatory cell stimulator that may address this underlying immune system imbalance in people with many autoimmune and inflammatory conditions. It is designed to target the interleukin-2 receptor complex in the body in order to stimulate proliferation of powerful inhibitory immune cells known as regulatory T cells. By activating these cells, REZPEG may act to bring the immune system back into balance. REZPEG is being developed as a self-administered injection for a number of autoimmune and inflammatory diseases.

About NKTR-255

NKTR-255 is a biologic that targets the IL-15 pathway in order to activate the body's innate and adaptive immunity. Through optimal engagement of the IL-15 receptor complex, NKTR-255 is designed to enhance functional NK cell populations and formation of long-term immunological memory, which may lead to sustained and durable anti-tumor immune response.

Preclinical findings suggest NKTR-255 has the potential to synergistically combine with antibody-dependent cellular cytotoxicity molecules as well as to enhance CAR-T therapies. A Phase 2/3 study is underway that combines NKTR-255 with approved CAR-T cell therapies in patients with diffuse large B-cell lymphoma, which is currently recruiting (NCT05664217).

There are two ongoing investigator sponsored trials (ISTs) evaluating NKTR-255 following treatment with a CAR-T cell therapy. Fred Hutchinson Cancer Center is conducting a Phase 1 study evaluating NKTR-255 in combination with CD19 CAR-T cell therapy in patients with relapsed or refractory large B-cell lymphoma (NCT05359211), and Stanford University is conducting a Phase 1 study evaluating NKTR-255 in combination with CD19/22 CAR-T cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (NCT03233854).

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements which can be identified by words such as: "will," "may," "advance," "support," "develop," "provide," "expect," "aim," "potential" and similar references to future periods. Examples of forward-looking statements include, among others, statements regarding the therapeutic potential of, and future development plans for rezpegaldesleukin, NKTR-255 and our other drug candidates in research programs, the prospects and plans for our collaborations with other companies, the timing of the initiation of clinical studies and the data readouts for our drug candidates, our expectations regarding our 2023 cost restructuring plan and reduction in our San Francisco-based workforce, including the anticipated cost savings and non-recurringcash payment related to, and the timing for completion of, the cost restructuring plan, and our expected working capital and cash runway. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results to differ materially from those indicated in the forward-looking statements include, among others: (i) our statements regarding the therapeutic potential of rezpegaldesleukin, NKTR-255 and our other drug candidates are based on preclinical and clinical findings and observations and are subject to change as research and development continue; (ii) rezpegaldesleukin, NKTR-255 and our other drug candidates are investigational agents and continued research and development for these drug candidates is subject to substantial risks, including negative safety and efficacy findings in ongoing clinical studies (notwithstanding positive findings in earlier preclinical and clinical studies); (iii) rezpegaldesleukin, NKTR-255 and our other drug candidates are in various stages of clinical development and the risk of failure is high and can unexpectedly occur at any stage prior to regulatory approval; (iv) the timing of the commencement or end of clinical trials and the availability of clinical data may be delayed or unsuccessful due to challenges caused by the COVID-19 pandemic, regulatory delays, slower than anticipated patient enrollment, manufacturing challenges, changing standards of care, evolving regulatory requirements, clinical trial design, clinical outcomes, competitive factors, or delay or failure in ultimately obtaining regulatory approval in one or more important markets; (v) we may not achieve the expected cost savings we expect from our 2022 corporate restructuring and reorganization plan or our 2023 cost restructuring plan and we may undertake additional restructuring and cost-saving activities in the future, (vi) patents may not issue from our patent applications for our drug candidates, patents that have issued may not be enforceable, or additional intellectual property licenses from third parties may be required; and (vii) certain other important risks and uncertainties set forth in our Annual Report on Form 10-K filed with the Securities and Exchange Commission on February 28, 2023. 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. We undertake no obligation to update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

Contact:

For Investors:Vivian Wu of Nektar Therapeutics628-895-0661

For Media:David Rosen of Argot Partners(212) 600-1902david.rosen@argotpartners.com

Cision

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Nektar Therapeutics Announces Strategic Reprioritization and Cost Restructuring Plan - Yahoo Finance

Immunology

Merck Strengthens Immunology Pipeline with Acquisition of … – Merck

April 16, 2023 6:00 am ET

PRA023 is a novel, late-stage candidate for ulcerative colitis and Crohns disease and other autoimmune conditions

Prometheus Biosciences comprehensive data set enables target discovery and precision medicine approach in inflammation and immunology

RAHWAY, N.J. & SAN DIEGO--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Prometheus Biosciences, Inc. (Prometheus) (Nasdaq: RXDX) today announced that the companies have entered into a definitive agreement under which Merck, through a subsidiary, has agreed to acquire Prometheus for $200.00 per share in cash for a total equity value of approximately $10.8 billion.

At Merck, we are committed to delivering on our purpose to save and improve lives and continue to identify and secure opportunities where compelling science and value creation align, said Robert M. Davis, chairman and chief executive officer, Merck. The agreement with Prometheus will accelerate our growing presence in immunology where there remains substantial unmet patient need. This transaction adds diversity to our overall portfolio and is an important building block as we strengthen the sustainable innovation engine that will drive our growth well into the next decade.

Prometheus is a clinical-stage biotechnology company pioneering a precision medicine approach for the discovery, development, and commercialization of novel therapeutic and companion diagnostic products for the treatment of immune-mediated diseases. The companys lead candidate, PRA023, is a humanized monoclonal antibody (mAb) directed to tumor necrosis factor (TNF)-like ligand 1A (TL1A), a target associated with both intestinal inflammation and fibrosis.

Prometheus was established to revolutionize the treatment of immune-mediated diseases through the application of a powerful precision medicine approach, said Mark McKenna, chairman and chief executive officer of Prometheus Biosciences. This agreement with Merck, a leader in biopharmaceutical research and development, allows Prometheus to maximize the potential for PRA023, while continuing to apply our technology and expertise to fuel further discoveries to address the needs of patients with immune disorders.

Prometheus is developing PRA023 for the treatment of immune-mediated diseases including ulcerative colitis (UC), Crohns disease (CD), and other autoimmune conditions. In December 2022, the company announced positive results for PRA023 from ARTEMIS-UC, a Phase 2, placebo controlled, study evaluating safety and efficacy in patients with moderate to severely active UC and APOLLO-CD a Phase 2A, open-label, study evaluating safety and efficacy in patients with moderate to severe CD. The findings were recently presented at the 18th Congress of European Crohns and Colitis Organisation (ECCO).

By applying a portfolio of powerful analytic tools to a comprehensive collection of IBD samples, Prometheus identified important disease insights that have now yielded a promising late-stage candidate, said Dr. Dean Y. Li, president, Merck Research Laboratories. I look forward to working with the talented Prometheus team to establish a new paradigm of precision treatment for immune diseases.

Under the terms of the acquisition agreement, Merck, through a subsidiary, will acquire all of the outstanding shares of Prometheus. The acquisition is subject to Prometheus Biosciences shareholder approval. The closing of the proposed transaction will be subject to certain conditions, including the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and other customary conditions. The transaction is expected to close in the third quarter of 2023.

A copy of the merger agreement pursuant to the transaction will be filed with the Securities and Exchange Commission (SEC) and will be publicly available. In addition, Merck and Prometheus will file annual, quarterly and current reports and other information with the SEC, which are available to the public from commercial document-retrieval services and at the SECs website at http://www.sec.gov. Copies of the documents filed with the SEC by Merck may be obtained at no charge on Mercks internet website at http://www.merck.com or by contacting Merck at 126 East Lincoln Avenue P.O. Box 2000, Rahway, NJ 07065 USA, or (908) 740-4000. Copies of the documents filed with the SEC by Prometheus may be obtained at no charge on Prometheus internet website at https://www.prometheusbiosciences.com or by contacting Prometheus at 3050 Science Park Road, San Diego, CA 92121 or (646) 241-4400.

Advisors

Morgan Stanley & Co. LLC acted as financial advisor to Merck in this transaction and Paul, Weiss, Rifkind, Wharton & Garrison LLP as its legal advisors. Centerview Partners LLC and Goldman Sachs & Co. LLC acted as financial advisors to Prometheus and Latham & Watkins LLP as the companys legal advisor.

About inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a term used to collectively describe Crohns disease and ulcerative colitis. These conditions are characterized by chronic inflammation of the gastrointestinal (GI) tract. Prolonged inflammation results in damage to the tissues lining the GI tract.Both ulcerative colitis and Crohn's disease usually are characterized by diarrhea, rectal bleeding, abdominal pain, fatigue and weight loss.

About PRA023

PRA023 is a humanized monoclonal antibody directed to tumor necrosis factor (TNF)-like ligand 1A (TL1A). PRA023 binds both soluble and membrane associated human TL1A with high affinity and specificity. Prometheus is developing PRA023 for the treatment of immune-mediated diseases including UC, CD, and other autoimmune conditions.

About Prometheus Biosciences

Prometheus Biosciences, Inc. is a clinical-stage biotechnology company pioneering a precision medicine approach for the discovery, development, and commercialization of novel therapeutic and companion diagnostic products for the treatment of immune-mediated diseases. The companys precision medicine platform, Prometheus360, combines proprietary machine learning-based analytical approaches with one of the worlds largest gastrointestinal bioinformatics databases to identify novel therapeutic targets and develop therapeutic candidates to engage those targets.

Investor Call

Merck will hold an investor call on Monday, April 17, at 8:00 a.m. EDT to discuss this proposed acquisition. Journalists who wish to ask questions are requested to contact a member of Mercks Media Relations team at the conclusion of the call. To listen to the call, please visit https://www.merck.com/investor-relations/events-and-presentations/.

About Merck

At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world - and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit http://www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

This news release of Merck & Co., Inc., Rahway, N.J., USA includes statements that are not statements of historical fact, or forward-looking statements, including with respect to Mercks proposed acquisition of Prometheus. Such forward-looking statements include, but are not limited to, the ability of Merck and Prometheus to complete the transactions contemplated by the merger agreement, including the parties ability to satisfy the conditions to the consummation of the merger contemplated thereby and the other conditions set forth in the merger agreement, statements about the expected timetable for completing the transaction, Mercks and Prometheuss beliefs and expectations and statements about the benefits sought to be achieved in Mercks proposed acquisition of Prometheus, the potential effects of the acquisition on both Merck and Prometheus, the possibility of any termination of the merger agreement, as well as the expected benefits and success of Prometheuss product candidates. These statements are based upon the current beliefs and expectations of Mercks management and are subject to significant risks and uncertainties. There can be no guarantees that the conditions to the closing of the proposed transaction will be satisfied on the expected timetable or at all, with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include, but are not limited to, uncertainties as to the timing of the merger; the risk that competing offers or acquisition proposals will be made; the possibility that various conditions to the consummation of the merger contemplated thereby may not be satisfied or waived (including the failure to obtain the requisite vote by Prometheuss stockholders); the effects of disruption from the transactions contemplated by the merger agreement and the impact of the announcement and pendency of the transactions on Prometheuss business; the risk that stockholder litigation in connection with the merger may result in significant costs of defense, indemnification and liability; general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Mercks ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Mercks patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Mercks 2022 Annual Report on Form 10-K and Mercks other filings with the Securities and Exchange Commission (SEC) available at the SECs Internet site (www.sec.gov).

Forward-Looking Statements of Prometheus Biosciences

Prometheus cautions readers that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on Prometheus current beliefs and expectations. Such forward-looking statements include but are not limited to statements regarding the companys plans to advance PRA023 into Phase 3 trials in UC and CD, including the timing thereof. The inclusion of forward-looking statements should not be regarded as a representation by Prometheus that any of its plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: topline results Prometheus reports are based on preliminary analysis of key efficacy and safety data, and such data may change following a more comprehensive review of the data related to the clinical trial and such topline data may not accurately reflect the complete results of a clinical trial; interim results of a clinical trial do not predict final results and the clinical outcomes may materially change following more comprehensive reviews of the data, as follow-up on the outcome of any particular patient continues and as more patient data become available, including from Cohort 2 of the ARTEMIS-UC trial; potential delays in the commencement, enrollment and completion of clinical trials and preclinical studies; the results of clinical trials are not necessarily predictive of future results; Prometheus dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; Prometheus ability to develop diagnostics for its therapeutic product candidates; unexpected adverse side effects or inadequate efficacy of its product candidates that may limit their development, regulatory approval and/or commercialization, or may result in recalls or product liability claims; planned future trials of PRA023 may not support regulatory registration; regulatory developments in the United States and foreign countries; Prometheus ability to maintain undisrupted business operations due to the COVID-19 pandemic, including delaying or otherwise disrupting its preclinical studies, clinical trials, manufacturing and supply chain; and other risks described in the companys prior press releases and filings with the Securities and Exchange Commission (SEC), including under the heading Risk Factors in Prometheus most recent annual report on Form 10-K and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Prometheus undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

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