Phase IIA, Single-Arm, Open- Label, Clinical Trial of Calcipotriene Plus 5-fluorouracil Immunotherapy for Skin Cancer Prevention in Organ Transplant Recipients

This phase IIA study evaluates the effects of calcipotriene plus 5- fluorouracil immunotherapy for skin cancer prevention in organ transplant recipients. Precancerous skin lesions, actinic keratoses (AK), may put organ transplant recipients at higher than average risk of developing skin cancer. Topical calcipotriene is a form of vitamin D and is used to treat psoriasis and topical 5- fluorouracil is a chemotherapy agent applied to the skin. The combination of calcipotriene plus 5- fluorouracil topical cream, which activates the immune cells against cancer, may help prevent skin cancer in organ transplant recipients who have precancerous skin lesions.

Start Date18 Aug 2024

Sponsor / Collaborator

National Cancer Institute

CTRI/2024/01/061889 / Not yet recruitingPhase 3

Comparative Evaluation of Vishataila & its modified form as an ointment with Calcipotriol ointment (0.005%) in the treatment of Dushivishjanya Kitibha Kushtha (Chronic Plaque Psoriasis). - NIL

Start Date01 Feb 2024

Sponsor / Collaborator

Mahatma Gandhi Ayurved College Hospital & Research Centre

ChiCTR2300077162 / SuspendedPhase 4

Sequential Therapy of Calcipotriol Ointment and Fluticasone Propionate Cream in Pediatric Psoriasis Patients: Efficacy Observation

Start Date01 Nov 2023

Sponsor / Collaborator-

100 Clinical Results associated with Calcipotriene

100 Translational Medicine associated with Calcipotriene

100 Patents (Medical) associated with Calcipotriene

1,507

Literatures (Medical) associated with Calcipotriene

31 Dec 2024·The Journal of dermatological treatment

Comparison of various excimer laser (EL) combination therapies for vitiligo: a systematic review and network meta-analysis

Review

Author: Li, XinHong ; Sun, Xiao ; Mu, ZengYi ; Shi, Lei ; Wang, XinYue ; Hu, Yue ; Li, ChanXiu ; Wang, YaPing

AIM:

This study aimed to compare the efficacy and safety of excimer laser (EL)-based combination regimens in improving repigmentation.

METHODS:

A comprehensive search was conducted in PubMed, Web of Science, Cochrane Library, and Embase on July 1, 2023, to include randomized controlled trials of EL combination treatments for vitiligo that met the criteria. The primary outcome measure was a repigmentation rate ≥ 75%, and the secondary outcome measures were a repigmentation rate of ≤ 25% and adverse events.

RESULTS:

Eleven studies involving 348 patients were included. Network Meta-Analysis showed that EL combined with antioxidants (SUCRA = 98.8%), EL combined with calcipotriol (SUCRA = 59.8%) and EL combined with tacalcitol (SUCRA = 59.6%) were the three optimal interventions achieving repigmentation rates ≥ 75%. EL alone (SUCRA = 77.6%), EL combined with tacalcitol (SUCRA = 61.7%) and EL combined with antioxidants (SUCRA = 57.2%) were the three interventions with the highest rates of treatment failure. Adverse events in all groups mainly included erythema, burning sensation and hyperpigmentation. Based on the results of the current study, EL combination therapies were safe with mild adverse events.

CONCLUSION:

EL combined with antioxidants was the preferred regimen for vitiligo, whereas EL alone was the regimen with the highest rate of treatment failure in vitiligo.

01 Apr 2024·Journal of ethnopharmacology

The therapeutic efficacy and mechanism action of Si Cao formula in the treatment of psoriasis: A pilot clinical investigation and animal validation

Article

Author: Fei, Xiaoya ; Ding, Xiaojie ; Li, Miao ; Song, Jiankun ; Luo, Ying ; Zheng, Qi ; Xie, Shaoqiong ; Wu, Xinxin ; Luo, Yue ; Li, Bin ; Kuai, Le ; Wang, Ruiping ; Jiang, Wencheng ; Ma, Xin ; Shen, Fang

ETHNOPHARMACOLOGICAL RELEVANCE:

Psoriasis is a chronic inflammation and relapsing disease that affected approximately 100 million individuals worldwide. In previous clinical study, it was observed that the topical application of Si Cao Formula (SCF) ameliorated psoriasis skin lesions and reduced the recurrence rate of patients over a period of three months. However, the precise mechanism remains unclear.

AIM OF THE STUDY:

The objective of this study was to assess the effectiveness and safety of SCF in patients diagnosed with psoriasis and explore the molecular mechanisms that contribute to SCF's therapeutic efficacy in psoriasis treatment.

MATERIALS AND METHODS:

A randomized, controlled, and pilot clinical study was performed. This study assessed 30 individuals diagnosed with mild to moderate plaque psoriasis. 15 of them underwent local SCF treatment, the others received calcipotriol intervention. The outcome measure focused on Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and recurrence rate. In addition, IMQ-induced psoriasis-like mice model were used to assess the impact of SCF on ameliorating epidermal hyperplasia, suppressing angiogenesis, and modulating immune response. Furthermore, we performed bioinformatics analysis on transcriptome data obtained from skin lesions of mice model. This analysis allowed us to identify the targets and signaling pathways associated with the action of SCF. Subsequently, we conducted experimental validation to confirm the core targets.

RESULTS:

Our clinical pilot study demonstrated that SCF could ameliorate skin lesions in psoriasis patients with comparable efficacy of calcipotriol in drop of PASI and DLQI scores. SCF exhibited a significantly reduced recurrence rate within 12 weeks (33.3%). Liquid Chromatography Mass Spectrometry (LC-MS) identified 41 active constituents of SCF (26 cations and 15 anions). Animal experiments showed SCF ameliorates the skin lesions of IMQ-induced psoriasis like mice model and suppresses epidermal hyperkeratosis and angiogenesis. There were 845 up-regulated and 764 down-regulated DEGs between IMQ and IMQ + SCF groups. GO analysis revealed that DEGs were linked to keratinization, keratinocyte differentiation, organic acid transport epidermal cell differentiation, and carboxylic acid transport interferon-gamma production. KEGG pathway analysis showed that SCF may play a vital part through IL-17 and JAK/STAT signaling pathway. In addition, SCF could reduce the number of positive cells expressing PCNA, CD31, pSTAT3, CD3, and F4/80 within the epidermis of psoriatic lesions, as well as the expression of Il-17a and Stat3 in IMQ-induced psoriasis mice.

CONCLUSIONS:

Our research suggests that SCF serves as a reliable and efficient local approach for preventing and treating psoriasis. The discovery of plausible molecular mechanisms and therapeutic targets associated with SCF may support its broad implementation in clinical settings.

Allergologia et immunopathologia

Resveratrol modulates the Nrf2/NF-κB pathway and inhibits TSLP-mediated atopic march

Article

Author: He, Quan ; Zhang, Liuchao ; Jiang, Jingxian ; Liu, Weihua ; Chen, Zi ; Wei, Guangfei ; Zhou, Linfu

Background: Resveratrol has been found to have anti-inflammatory and anti-allergic properties. The effects of resveratrol on thymic stromal lymphopoietin (TSLP)-mediated atopic march remain unclear. Purpose: To explore the potential role of resveratrol in TSLP-mediated atopic march. Methods: The atopic march mouse model was established by topical application of MC903 (a vitamin D3 analog). Following the treatment with resveratrol, airway resistance in mice was discovered by pulmonary function apparatus, and the number of total cells, neutrophils, and eosinophils in bronchoalveolar lavage fluid was counted. The histopathological features of pulmonary and ear skin tissues, inflammation, and cell infiltration were determined by hematoxylin and eosin staining. The messenger RNA (mRNA) levels of TSLP, immunoglobulin E, interleukin (IL)-4, IL-5, and IL-13 were measured by real-time quantitative polymerase chain reaction. The protein expression of nuclear factor kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling-associated molecules (p-p65, p65, p-I kappa B kinase alpha (IκBα), IκBα, Nrf2, and TSLP) in lung and ear skin tissues were assessed by Western blot analysis. Results: Resveratrol attenuated airway resistance and infiltration of total cells, eosinophils, and neutrophils in both lung and ear skin tissues. Resveratrol ameliorates serum inflammatory markers in allergic mice. Moreover, the phosphorylation levels of NF-κB pathway-related proteins were significantly reduced by administration of resveratrol in allergic lung and ear skin tissues. Similarly, the protein expression of TSLP in both lung and ear skin tissues was reduced by resveratrol, and Nrf2, a protector molecule, was increased with resveratrol treatment. Conclusion: Resveratrol attenuates TSLP-reduced atopic march through ameliorating inflammation and cell infiltration in pulmonary and ear skin tissues by inhibiting the abnormal activation of NF-κB signaling pathway.

News (Medical) associated with Calcipotriene

20 May 2024

·www.prnewswire.com

Studies Show Linked Biological Pathways Driving Skin Inflammation

NEW YORK, May 20, 2024 /PRNewswire/ -- A certain biological pathway, a set of linked reactions in the body, drives the inflammation seen in the skin disease psoriasis, a new study finds. The work could lead to improved therapies for all inflammatory skin diseases, including atopic and allergic dermatitis and a type of boil called hidradenitis suppurativa, say the study authors. Inflammation is the body's natural response to irritation and infection, but when out of control, it can lead to the reddish, flaky, itchy lesions that come with these skin diseases. Led by researchers at NYU Langone Health, the new study found that the interleukin-17 (IL-17) pathway, whose activity is blocked by existing anti-inflammatory drugs, activates a protein called hypoxia inducible factor 1-alpha (HIF-1-alpha) in psoriasis. Researchers say that IL-17 has long been known to be active in inflammation, but the role of HIF-1-alpha has until now been unclear. The research team also found that HIF-1-alpha let inflamed skin cells more actively break down sugar for energy, supporting their metabolism and leading to the production of a waste product called lactate. When consumed by inflammatory T cells, lactate triggered production of IL-17, fueling even more inflammation. Publishing in the journal Immunity online May 20, the findings show that in human skin tissue samples from people with psoriasis, measures of gene activity around IL-17 and HIF-1-alpha were similar, suggesting that these factors are interconnected. Experiments in mice treated to develop psoriasis found that subsequent treatment with an experimental drug that blocks the action of HIF-1-alpha, called BAY-87-2243, resolved inflammatory skin lesions. Further, skin samples from 10 patients successfully treated with anti-inflammatory drug etanercept showed diminished activity for both IL-17 and HIF-1-alpha, suggesting to researchers that when IL-17 is blocked, so is HIF-1-alpha. "Our study results broadly show that activation of HIF-1-alpha is at the crux of metabolic dysfunction observed in psoriasis and that its action is triggered by IL-17, another key inflammatory-signaling molecule," said corresponding study author Shruti Naik, PhD, associate professor at NYU Grossman School of Medicine in the Departments of Pathology and Medicine, and the Ronald O. Perelman Department of Dermatology. Further experiments were performed on skin samples from five patients with psoriasis whose healthy and inflamed skin was separately treated with either BAY-87-2243 or an existing combination of topical drugs (calcipotriene and betamethasone dipropionate). Researchers then compared differences in inflammatory gene activity as a measure of impact and found that the HIF-1-alpha inhibitor had a greater effect than existing topical drugs. Specifically, skin samples that responded to HIF-1-alpha therapy had 2,698 genes that were expressed differently, while standard-of-care–treated samples had 147 differently expressed genes. Genetic analysis of skin samples from another 24 psoriatic patients treated with the IL-17A–blocking drug secukinumab showed only decreased, not heightened, gene activity connected to HIF-1-alpha when compared to HIF-1-alpha gene activity in nine healthy patients with no psoriatic disease. Researchers say this indicates HIF-1-alpha's blocked action was codependent on blockage of IL-17. Additional experiments in mice showed that blocking sugar (glucose) uptake in the skin slowed psoriatic disease growth by limiting glucose metabolism, or glycolysis. Both the number of immune T cells tied to inflammation and the cell levels of IL-17 also decreased. The researchers found further that levels of lactate, the main byproduct of glycolysis, in psoriatic skin cell cultures dropped once exposed to the glycolysis-inhibiting drug 2-DG. Directly targeting lactate production in psoriatic mice using a topical skin cream containing lactate dehydrogenase, which breaks down lactate, also slowed disease progression in the skin, with reduced numbers of inflammatory gamma-delta T cells and reduced IL-17 activity. Gamma-delta T cells were shown to take up lactate and use it to produce IL-17. "Our findings suggest that blocking either HIF-1-alpha's action or its glycolytic metabolic support mechanisms could be effective therapies for curbing the inflammation," added Naik, who is also the associate director for NYU Langone's Judith and Stewart Colton Center for Autoimmunity. "Evidence of HIF-1-alpha's depressed action, or downregulation, could also serve as a biomarker, or molecular sign, that other anti-inflammatory therapies are working," said study co-senior investigator Jose U. Scher, MD, the Steere Abramson Associate Professor of Medicine in the Department of Medicine at NYU Grossman School of Medicine. Scher, who also serves as director of NYU Langone's Psoriatic Arthritis Center and the Judith and Stewart Colton Center for Autoimmunity, says the team plans to develop experimental drugs that can block HIF-1-alpha and lactate action in the skin "to end the underlying vicious cycle of IL-17–driven inflammation in skin disease. Our research fundamentally expands the scope of feasible therapeutic options." Naik points out that while many available therapies for psoriasis, including steroids and immunosuppressive drugs, reduce inflammation and symptoms, they do not cure the disease. She said further experiments are needed to refine which experimental drug works best, with respect to HIA-1-alpha inhibition, before clinical trials could start. Indeed, Naik and study co-lead investigators Ipsita Subudhi and Piotr Konieczny have a patent application pending (U.S. application number 63/540,794) for inflammatory skin disease therapies derived from their work on HIA-1-alpha inhibition. More than 8 million Americans and 125 million worldwide are estimated to have psoriatic disease. The condition affects men and women equally. Funding support for the studies was provided by National Institutes of Health grants P30AR075043, R01AR080436, R01AI168462, UC2AR081029, K22AI135099, K99AR083536, T32AR069515, TL1TR001447, UL1TR001445, and DP2AR079173. Additional funding was provided by the National Psoriasis Foundation, the Judith and Stewart Colton Center for Autoimmunity, the Beatrice Snyder Foundation, the Riley Family Foundation, the American Association of Immunologists, the International Human Frontier Science Program, the Charles H. Revson Foundation, and the Pew-Stewart Scholar Award 00034119, as well as the New York Stem Cell Foundation. Naik serves on the advisory boards of Seed Inc. and as a consultant for BiomX. She also receives research funding from Takeda Pharmaceuticals. Scher has served as a consultant for Janssen, Pfizer, UCB, and BMS. He also receives research funding from Janssen and Pfizer. All of these arrangements are being managed in accordance with the policies and practices of NYU Langone Health. Besides Naik, Scher, Subudhi, and Konieczny, other NYU Langone investigators were Aleksandr Prystupa, Rochelle Castillo, Erica Sze-Tu, Yue Xing, Daniel Rosenblum, Ilana Reznikov, Ikjot Sidhu, Cynthia Loomis, Catherine Lu, and Aristotelis Tsirigos. Other study co-investigators were Niroshana Anandasabapathy, at Weill Cornell Medicine; Mayte Suarez-Farinas, at the Icahn School of Medicine at Mount Sinai; and Johann Gudjonsson, at the University of Michigan. Contact: Gregory Williams, [email protected] SOURCE NYU Langone Health

Clinical Result

02 May 2024

·www.globenewswire.com

Kymera Therapeutics Announces First Quarter 2024 Financial Results and Provides a Business Update

KT-474/SAR444656 (IRAK4) Phase 2 clinical trials ongoing in HS and AD with data expected in the first half of 2025 KT-621 (STAT6) expected to start Phase 1 in the second half of 2024 and KT-294 (TYK2) expected to start Phase 1 in the first half of 2025, both with Phase 1 data in 2025 KT-253 (MDM2) and KT-333 (STAT3) Phase 1 dose escalation studies ongoing with clinical data updates at ASCO and EHA, respectively Well-capitalized with $745 million in cash as of March 31, 2024, and runway into the first half of 2027 Company to hold call and webcast today at 8:30 a.m. ET WATERTOWN, Mass., May 02, 2024 (GLOBE NEWSWIRE) -- Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage biopharmaceutical company advancing a new class of small molecule medicines using targeted protein degradation (TPD), today reported financial results for the first quarter ended March 31, 2024, and provided business highlights and updates on its pipeline of protein degraders. “This was an important quarter for Kymera as we are poised to expand our clinical pipeline with an increased focus on immunology. With our STAT6 and TYK2 oral degrader programs, we believe we can significantly impact the way complex immuno-inflammatory diseases are managed with medicines that have the potential to offer biologics-like efficacy with the convenience of oral, daily pills,” said Nello Mainolfi, PhD, Founder, President, and CEO. “Building on our prior scientific achievements in both immunology and oncology, we have established a strong foundation and an industry-leading pipeline positioning Kymera to deliver first-in-class therapies to patients around the world.” Business Highlights, Recent Developments and Upcoming Milestones KT-474/SAR444656 IRAK4 Degrader Enrollment is ongoing in the two randomized, placebo-controlled Phase 2 trials being conducted by Sanofi, evaluating KT-474 for the treatment of hidradenitis suppurativa (HS) and atopic dermatitis (AD). Topline data is expected to be reported in the first half of 2025. KT-621 STAT6 Degrader Kymera unveiled its first-in-class oral STAT6 degrader, KT-621, at its Immunology R&D Day in January 2024. KT-621 is a once daily, oral STAT6 degrader with the potential to deliver dupilumab-like activity in multiple diseases including atopic dermatitis, asthma, and chronic obstructive pulmonary disorder (COPD), among others. The Company expects to initiate a Phase 1 clinical trial with KT-621 in the second half of 2024 and report the Phase 1 results in the first half of 2025.In March 2024, Kymera presented a poster highlighting preclinical data for KT-621 at the American Academy of Dermatology (AAD) Annual Meeting. Preclinical findings showed that KT-621 was exquisitely selective for STAT6 over other STATs and fully blocked IL-4/IL-13 functions in key human TH2 cellular assays with picomolar potency that was superior to dupilumab. At low daily oral doses, KT-621 demonstrated near full in vivo STAT6 degradation in disease-relevant tissues that was well-tolerated. In an MC903-induced atopic dermatitis mouse model, KT-621 demonstrated robust degradation of STAT6 in spleen and marked reduction of total serum IgE comparable to the activity of dupilumab. These data demonstrate the potential of KT-621 for the treatment of atopic dermatitis and other allergic diseases.The Company plans to share new additional KT-621 preclinical data at upcoming medical meetings, including the American Thoracic Society International Conference, being held May 17-22, 2024, in San Diego, CA, and Digestive Disease Week, being held May 18-21, 2024, in Washington, DC. KT-294 TYK2 Degrader Kymera unveiled its first-in-class oral TYK2 degrader, KT-294, at its Immunology R&D Day in January 2024. KT-294 is a once daily, oral TYK2 degrader with the potential to deliver biologics-like activity in conditions such as inflammatory bowel disease, psoriasis, psoriatic arthritis, and lupus, among others. The Company expects to initiate a Phase 1 clinical trial with KT-294 in the first half of 2025 and report the Phase 1 results in the second half of 2025.In March 2024, Kymera presented a poster highlighting preclinical data for KT-294 at the AAD Annual Meeting. In preclinical testing, KT-294 demonstrated picomolar degradation potency and potent inhibition of the IL-23, IL-12 and Type I IFN pathways, showing its potential to recapitulate the biology of human TYK2 loss-of-function mutations. KT-294 did not impact any of the other Janus kinase (JAK) proteins and therefore, unlike the TYK2 small molecule inhibitor deucravacitinib, spared IL-10 signaling, a feature important in the treatment of inflammatory bowel disease. In addition, in preclinical studies, TYK2 degradation led to superior inhibition of the Type I IFN pathway compared to TAK-279, which is relevant to the treatment of interferonopathies like lupus. This biological differentiation of KT-294 compared to TYK2 small molecule inhibitors, combined with its ability to provide deep and sustained TYK2 knockdown in vivo with low daily oral doses, has the potential to deliver a best-in-class TYK2 profile.The Company plans to share additional preclinical data at upcoming medical meetings. KT-253 MDM2 Degrader The dose escalation portion of the Phase 1a clinical trial in liquid and solid tumors is ongoing. Kymera will present KT-253 clinical data updates in a poster at the upcoming American Society of Clinical Oncology (ASCO) meeting being held May 31 – June 4, 2024, in Chicago, Illinois. The Company expects to complete the MDM2 Phase 1a study and share the full data set later in 2024 at a medical meeting.Kymera is also developing a biomarker-based patient selection strategy for subsequent development beyond Phase 1a and will present data at a medical meeting this year. KT-333 STAT3 Degrader In April 2024 at the American Association for Cancer Research (AACR) Annual Meeting, Kymera presented new preclinical data in a late-breaking research session showing the structural and molecular mechanisms underlying the anti-tumor activity of its novel STAT3 degrader, KT-333, and for the first time, disclosed VHL as the ideal E3 ligase for potent, selective, rapid, and consistent STAT3 degradation in cancer models.The dose escalation portion of the Phase 1a clinical trial in liquid and solid tumors is ongoing. Kymera will present KT-333 clinical data updates in a poster at the upcoming European Hematology Association (EHA) meeting being held June 13-16, 2024, in Madrid, Spain. The Company expects to complete the Phase 1a study and share the full data set later in 2024 at a medical meeting. Corporate Updates In January 2024, the Company announced the closing of its upsized underwritten equity offering, resulting in net proceeds of approximately $301 million. With these proceeds, the Company extended its cash runway into the first half of 2027.In February 2024, Kymera relocated to its new corporate headquarters in Watertown, MA, to support the growing organization and scale critical research and development capabilities to enable the expansion and progress of the Company’s innovative pipeline.Juliet Williams, PhD, Head of Research, presented the opening keynote at the Society of Laboratory Automation and Screening (SLAS) Annual Meeting in February 2024, discussing Kymera’s industry-leading research and portfolio of degraders.Nello Mainolfi, PhD, Founder, President and CEO, presented in a Major Symposium at the AACR Annual Meeting in April 2024 highlighting the Company’s unique target selection strategy and strong preclinical to clinical translation observed with its first-in-class oncology programs. Program Background Information For more information on Kymera’s pipeline visit our website. Financial Results Collaboration Revenues: Collaboration revenues were $10.3 million for the first quarter of 2024, compared to $9.5 million for the same period of 2023. Collaboration revenues in the first quarter of 2024 were all attributable to the Company’s Sanofi collaboration. Research and Development Expenses: Research and development expenses were $48.8 million for the first quarter of 2024, compared to $42.2 million for the same period of 2023. This increase was primarily due to increased expenses related to the investment in the Company’s platform and discovery programs, as well as an increase in occupancy and related costs due to continued growth in the research and development organization. Stock based compensation expenses included in R&D were $6.1 million for the first quarter of 2024, compared to $4.7 million for the same period in 2023. General and Administrative Expenses: General and administrative expenses were $14.4 million for the first quarter of 2024, compared to $12.6 million for the same period of 2023. The increase in annual expense was primarily due to increase in legal and professional service fees in support of the Company’s growth and an increase in personnel, facility, occupancy, and other expenses from an increase in headcount to support growth as a public company. Stock based compensation expenses included in G&A were $5.9 million for the first quarter of 2024 compared to $4.7 million for the same period in 2023. Net Loss: Net loss was $48.6 million for the first quarter of 2024 compared to a net loss of $40.9 million for the same period of 2023. Cash and Cash Equivalents: As of March 31, 2024, Kymera had approximately $745 million in cash, cash equivalents, and investments. Kymera expects that its cash and cash equivalents will provide the Company with an anticipated cash runway into the first half of 2027. Its existing cash is expected to take the Company beyond the Phase 2 data for KT-474, as well as additional proof-of-concept data for KT-253 and KT-333, and several clinical inflection points for its STAT6 and TYK2 programs while Kymera continues to identify opportunities to accelerate growth and expand its pipeline, technologies and clinical indications. Conference Call Kymera will host a conference call and webcast today, May 2, 2024, at 8:30 a.m. ET. To access the conference call via phone, please dial +1 (833) 630-2127 or +1 (412) 317-1846 (International) and ask to join the Kymera Therapeutics call. A live webcast of the event will be available under News and Events in the Investors section of the Company’s website at www.kymeratx.com. A replay of the webcast will be archived and available following the event for three months. About Kymera TherapeuticsKymera is a clinical-stage biotechnology company pioneering the field of targeted protein degradation (TPD) to develop medicines that address critical health problems and have the potential to dramatically improve patients’ lives. Kymera is deploying TPD to address disease targets and pathways inaccessible with conventional therapeutics. Having advanced the first degrader into the clinic for immunological diseases, Kymera is focused on delivering oral small molecule degraders to provide a new generation of convenient, highly effective therapies for patients with these conditions. Kymera is also progressing degrader oncology programs that target undrugged or poorly drugged proteins to create new ways to fight cancer. Founded in 2016, Kymera has been recognized as one of Boston’s top workplaces for the past several years. For more information about our science, pipeline and people, please visit www.kymeratx.com or follow us on X (previously Twitter) or LinkedIn. Cautionary Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements by Kymera Therapeutics regarding its: strategy, business plans and objectives for its clinical programs; plans and timelines for the preclinical and clinical development of its product candidates, including the therapeutic potential, clinical benefits and safety thereof; expectations regarding timing, success and data announcements of current ongoing preclinical and clinical trials; the ability to initiate new clinical programs; and Kymera's financial condition and expected cash runway into the first half of 2027. The words "may," "might," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "expect," "estimate," "seek," "predict," "future," "project," "potential," "continue," "target" and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: the timing and anticipated results of our current and future preclinical studies and clinical trials, supply chain, strategy and future operations; the delay of any current and future preclinical studies or clinical trials or the development of Kymera Therapeutics' drug candidates; the risk that the results of current preclinical studies and clinical trials may not be predictive of future results in connection with current or future preclinical and clinical trials, including those for KT- 474/SAR444656, KT-621, KT-294, KT-333 and KT-253; Kymera Therapeutics' ability to successfully demonstrate the safety and efficacy of its drug candidates; the timing and outcome of the Kymera Therapeutics' planned interactions with regulatory authorities; obtaining, maintaining and protecting its intellectual property; the risks associated with pandemics or epidemics; and Kymera Therapeutics' relationships with its existing and future collaboration partners. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in the Annual Report on Form 10-K for the period ended December 31, 2023, and most recent Quarterly Report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in Kymera Therapeutics' subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Kymera Therapeutics' views only as of today and should not be relied upon as representing its views as of any subsequent date. Kymera Therapeutics explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. KYMERA THERAPEUTICS, INC. Consolidated Balance Sheets (In thousands, except share and per share amounts) (Unaudited) March 31, 2024 December 31, 2023 Assets Cash, cash equivalents and marketable securities $744,934 $436,315 Property and equipment, net 49,336 48,134 Right-of-use assets, operating lease 49,329 52,945 Other assets 24,652 38,365 Total assets $868,251 $575,759 Liabilities and Stockholders’ Equity Deferred revenue $46,394 $54,651 Operating lease liabilities 84,732 82,096 Other liabilities 25,922 44,041 Total liabilities 157,048 180,788 Total stockholders’ equity 711,203 394,971 Total liabilities and stockholders’ equity $868,251 $575,759 KYMERA THERAPEUTICS, INC.Consolidated Statements of Operations(In thousands, except share and per share amounts)(Unaudited) Three Months Ended March 31, 2024 2023 Collaboration Revenue$10,287 $9,466 Operating expenses: Research and development$48,819 $42,227 General and administrative 14,374 12,565 Impairment of long-lived assets 4,925 — Total operating expenses 68,118 54,792 Loss from operations (57,831) (45,326)Other income (expense): Interest and other income 9,343 4,453 Interest and other expense (69) (55)Total other income 9,274 4,398 Net loss attributable to common stockholders$(48,557) $(40,928)Net loss per share attributable to common stockholders, basic and diluted$(0.69) $(0.70)Weighted average common stocks outstanding, basic and diluted 70,770,320 58,187,038 Investor & Media Contact: Justine KoenigsbergVice President, Investor Relationsinvestors@kymeratx.commedia@kymeratx.com 857-285-5300

Phase 1AACRFinancial StatementPhase 2ASCO

14 Mar 2024

·www.prnewswire.com

Psoriasis in America - Insights into Psoriasis Patient Demographics, Quality of Life, Information-seeking Behaviors, HCP Engagement and Treatment Experiences

DUBLIN, March 14, 2024 /PRNewswire/ -- The "Psoriasis in America 2023: Understanding the Psoriasis Patient Experience" report has been added to ResearchAndMarkets.com's offering. Approximately 7.5 million people in the United States have psoriasis. This Psoriasis in America report provides a comprehensive look at life for those living with psoriasis. Using detailed quantitative data, it gives a full picture of the psoriasis patient experience - from symptoms to treatment to HCP relationships to quality of life - so you can make informed, strategic decisions, identify opportunities, and understand potential challenges. The report offers an in-depth look at the psoriasis patient experience. This large-scale, patient-reported data leverages vital quantitative insights essential to understanding key touchpoints in the psoriasis patient journey, including condition management, HCP engagement, quality of life, treatment experience and satisfaction, and much more. This report lifts the curtain on life with psoriasis, giving stakeholders an actionable look at the behaviors, attitudes, perceptions, needs, and experiences of people living with the condition. Data can be used to inform strategic decisions, including product communications, competitive assessments, concept development, landscape analyses, patient journey overlays, and forecasting inputs. This report also addresses important questions that stakeholders may not even know to ask while offering valuable insights into must-have patient-reported data points not available anywhere else. Add-on custom data analysis opportunities are also available for an additional cost - please see the report following purchase for more information. The analyst reaches millions of people through its portfolio of 45+ condition-specific online health communities - including PlaquePsoriasis.com - to provide information, connection, and support to patients and caregivers in the U.S. This report includes a deep-dive into: Psoriasis patient demographics Age, gender, ethnicity, marital status, children, employment status, income, location, insurance, and other health conditions Impact of psoriasis on quality of life Severity, impact on quality of life, symptoms experienced, and what patients wish others better understood Information-seeking behaviors Information sources used, plus topics of interest HCP engagement Primary HCP seen for condition, satisfaction with HCP, and discussion about brands aware of/not used Psoriasis treatment awareness and experiences Aided awareness of specific treatments, treatment experience, satisfaction with current treatments, perceived control with current treatment plan, and interest/participation in clinical trials Key questions answered in this report: To what extent do people say psoriasis impacts their overall quality of life? What's the average number of flares in the past year? What do patients wish others understood about psoriasis? What percentage of patients see a specialist for psoriasis treatment? What treatments have the highest aided brand awareness among patients? What percentage of patients use a biologic? How many patients feel their psoriasis is well-controlled on their current treatment plan? What percentage of patients are likely to switch or add new treatments in the next six months? What medications have patients discussed with their HCP? What are the top online resources people with psoriasis use to find information? What kinds of content and information do patients search for? What percentage of patients search for information on treatment options? Methodology Psoriasis in America consists of: A 20-minute online quantitative survey, covering demographics, comorbidities, quality of life/impact, HCP interactions, as well as treatment awareness, experiences, and discussions Qualitative patient insights from open-ended responses Additional details: Fielded: January 16, 2023 to April 14, 2023 Convenience sample of 490 respondents diagnosed with psoriasis Respondents are age 18+, living in the U.S., and are recruited from proprietary online health communities and recruiting partners Key Topics Covered: Respondent Demographics Research Highlights Condition Status and Quality of Life Severity and Exacerbations Symptoms Experienced Impact on Quality of Life Qualitative Patient Insights Information-Seeking Behaviors Resources Used to Manage Health Types of Content/Information Sought Treatment Awareness and Experiences Primary HCP Seen for Psoriasis Care Aided Brand Awareness of Treatments Treatment Usage Condition Control on Current Treatment and Clinical Trial Interest Treatment Discussions with HCP Appendix with All Data Charts and Distributions Brands and treatments mentioned in this report include: Topical corticosteroid (such as hydrocortisone) BRYHALIT (halobetasol propionate) lotion DesOwen (desonide) SERNIVOT (betamethasone dipropionate) SORILUXT Foam (calcipotriene) TACLONEX (calcipotriene and betamethasone) TAZORAC (tazarotene) VECTICAL (calcitriol) VTAMA (tapinarof) ZITHRANOLT-RR (anthralin) ZORYVET (roflumilast) Acitretin (SORIATANE) ARAVA (leflunomide) Azathioprine (such as IMURAN, AZASAN) Cyclosporine (such as Sandimmune, NEORAL, RESTASIS) Methotrexate (eg, Rheumatrex), also sometimes given as an injection OTEZLA (apremilast) PLAQUENIL (hydroxychloroquine) RINVOQ (upadacitinib) SOTYKTUT (deucravacitinib) Sulfasalazine (Azulfidine) XELJANZ/XELJANZ XR (tofacitinib citrate) AMJEVITAT (adalimumab-atto) Hide until launched in US AVSOLA (infliximab-axxq) CIMZIA (certolizumab) COSENTYX (secukinumab) CYLTEZO (adalimumab-adbm) Hide until launched in US ENBREL (etanercept) ERELZIT (etanercept-szzs) Hide until launched in US HULIO (adalimumab-fkjp) Hide until launched in US HUMIRA (adalimumab) HYRIMOZ (adalimumab-adaz) Hide until launched in US ILUMYAT (tildrakizumab-asmn) INFLECTRA (infliximab-dyyb) IXIFIT (infliximab-qbtx) Hide until launched in US ORENCIA (abatacept) REMICADE (infliximab) RENFLEXIST (infliximab-abda) SIMPONI (golimumab) SIMPONI ARIA (golimumab for infusion) SILIQT (brodalumab) SKYRIZI (risankizumab-rzaa) STELARA (ustekinumab) TALTZ (ixekizumab) TREMFYA (guselkumab) For more information about this report visit About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends. Media Contact: Research and Markets Laura Wood, Senior Manager [email protected] For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716 Logo: SOURCE Research and Markets

100 Deals associated with Calcipotriene

External Link

KEGG	Wiki	ATC	Drug Bank
D01125	Calcipotriene	D05AX02	DB02300

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Psoriasis vulgaris	JP	Leo Pharma, Inc.	18 Jan 2000
Plaque psoriasis	US	LEO Pharma A/S	29 Dec 1993
Psoriasis	-	Leo Pharma, Inc.	01 Jan 1990

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03308799 (Biospace) Manual	Phase 3	Skin Pigmentation	-	Calcipotriene+Betamethasone Dipropionate/Calcipotriene (Patients with skin of color (Fitzpatrick IV-VI))	uokoxcxnoi(sgweycbmdp) = yiputinovj lsvmntaoel (gfylyqeknm ) View more	Positive	15 Sep 2022
EADV2022	Phase 3	Plaque psoriasis	-	Calcipotriene (CAL) and betamethasone dipropionate (BDP) cream	tfzpyxdybi(qetecvcqbk) = spuhyywzwv eewirigzgx (ilkhqseznl ) View more	-	07 Sep 2022
				Vehicle	tfzpyxdybi(qetecvcqbk) = potshtgwtf eewirigzgx (ilkhqseznl ) View more
phase 3 (EADV2022)	Phase 3	Plaque psoriasis	796	Calcipotriene and betamethasone dipropionate cream	iqyqsidnlb(jpbcwrrbiv) = bbzfnbanes fglnkijzcg (lwlqgwyyln ) View more	Positive	07 Sep 2022
				Calcipotriene and betamethasone dipropionate gel	iqyqsidnlb(jpbcwrrbiv) = muivjulxot fglnkijzcg (lwlqgwyyln ) View more
EADV2022	Phase 3	Psoriasis of scalp	-	CAL/BDP cream	omljzfbekf(zygnvlkydg) = izvciexibr weoednmwqe (ikadudaamv ) View more	-	07 Sep 2022
				Vehicle cream	omljzfbekf(zygnvlkydg) = jssstuwugz weoednmwqe (ikadudaamv ) View more
Pubmed Manual	Not Applicable	Psoriasis vulgaris	166	Calcipotriene+LEO90100	znicoswlyr(uwfdrhtopr) = linvmwwckb qivhgnkysb (axogjjrawx, 3.0) View more	Positive	18 Jul 2022
EADV 12022 \| EADV 22022	Not Applicable	Plaque psoriasis	-	Calcipotriol 50 µg/g plus betamethasone dipropionate 0.5 mg/g aerosol foam	wzewhbntuq(jbvosmmdfe) = ikptanhcij mwyrsoykol (rhpahohzxy )	-	12 May 2022
				Calcipotriol 50 µg/g plus betamethasone dipropionate 0.5 mg/g cream	wzewhbntuq(jbvosmmdfe) = erimdwoeml mwyrsoykol (rhpahohzxy )
NCT02899962 (PSO-LONG trial, Pubmed \| J Am Acad Dermatol) Manual	Phase 3	Plaque psoriasis	545	Cal/BD foam	stsdoeanja(jteuioriws) = irxrpcpdnv lubxjgutif (iadytsklnx ) View more	Superior	01 May 2021
				vehicle foam	stsdoeanja(jteuioriws) = kifzirzcdf lubxjgutif (iadytsklnx ) View more
NCT02387853 (Pubmed \| J Eur Acad Dermatol Venereol) Manual	Phase 2	Plaque psoriasis	106	Cal/BD foam	sxnzujdkfv(hjqxlaohyf) = tbybruqjwo nnlgicnevc (iqgpltyhbh ) View more	Positive	01 Sep 2020
NCT01694433 (CTgov)	Phase 2/3	Acne Vulgaris	66	Calcipotriene (Calcipotriene Cream)	wmyzmslvcu(musvzritru) = mwglksomhz inywxaexuv (fozbdstztx, eerzocrbzw - ewlthhjcdg) View more	-	07 May 2019
				placebo (Placebo)	wmyzmslvcu(musvzritru) = oowjegkkno inywxaexuv (fozbdstztx, uqjpkekewj - brkwlajkot) View more
NCT02411643 (CTgov)	Early Phase 1	Scleroderma, Localized	2	topical calcipotriene 0.005% ointment	icgrutirhn(zhyffqtsut) = nkrsncxtdc owrgnwybzi (hzoyhqqtsw, aqyacpjxao - pgnbosbrhb) View more	-	13 Sep 2018

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