Epidermal growth factor receptor (EGFR) signaling plays a key role in regulating epidermal cell proliferation, survival, and differentiation. Keratins form a scaffold with epidermal desmosomes that involves ErbB/ EGFR signaling and keratin deficiency makes keratinocytes more sensitive to EGFR activation. Erlotinib, an EGFR inhibitor, was approved 20 years ago for cancer treatment and is generally used at 150 mg daily in adults >50 kg. While gastrointestinal and cutaneous side effects commonly occur at doses of 150 mg, adverse events occur less often at lower doses. We first reported erlotinib as effective for Olmsted syndrome, a rare hereditary EDD with painful PPK that results from variants in TRPV3. Erlotinib is now the treatment of choice for children and adults with Olmsted syndrome. Erlotinib is thought to inhibit formation of a complex that includes TRPV3, EGFR, and its primary skin-based ligand, TGF-a, which in turn regulates keratinocyte proliferation and differentiation. High-throughput screening to identify compounds that stabilize keratin filaments have also pointed to the EGFR pathway for targeting. Reviews and recent case reports have suggested the benefit of erlotinib for PC,
Given these preliminary data, we hypothesize that EGFR activation is a characteristic feature of keratinopathies. Further, we expect that oral low-dose erlotinib will improve the scaling and skin thickening of the spectrum of keratinopathies and be tolerated by most patients. For those who experience pain, particularly from plantar involvement, we predict that erlotinib therapy will improve mobility and pain. Finally, we aim to find the mechanism by which erlotinib improves the phenotypes of the various keratinopathies to better understand these disorders and predict response. We will look specifically at the impact on differentiation vs. hyperproliferation and barrier function, as well as the immune modulatory effects of the erlotinib using a multi-omics approach.

Start Date01 Dec 2025

Sponsor / Collaborator

Northwestern University

[+1]

NCT04172779

/ Not yet recruitingPhase 2IIT

Phase IIa Single-arm Clinical Trial of Hepatocellular Carcinoma Chemoprevention With Low-dose Erlotinib in Patients With Liver Cirrhosis

This phase IIa trial studies long-term low-dose erlotinib hydrochloride treatment to assess its efficacy and safety to prevent development of hepatocellular carcinoma in patients with liver cirrhosis.

Start Date01 Jul 2025

Sponsor / Collaborator

The University of Texas Southwestern Medical Center

[+1]

NCT06483555

/ Not yet recruitingPhase 1/2IIT

Subjects With Advanced Basal-like Pancreatic Adenocarcinoma Treated With Gemcitabine, Erlotinib and Nab-paclitaxel (PANGEA) Versus Subjects With Classical Pancreatic Adenocarcinoma Treated With Triplet Standard of Care Therapy.

This study explores the best dose of the combination treatment for subjects with advanced unresectable or metastatic basal-like subtype pancreatic adenocarcinoma. For that reason, the safety, efficacy, and tolerability, as well as preliminary estimates of anti-tumor effects of low-dose epidermal growth factor receptor EGFR inhibitors in combination with bi-weekly gemcitabine/nab-paclitaxel (GnP) will be examined in subjects with advanced basal-like pancreatic adenocarcinoma.
The Purity Independent Subtyping of Tumors (PurIST) will determine the type of cancer either "basal type" or "classical". If cancer subtype-based first-line chemotherapy in combination with erlotinib will be safe and tolerable in subjects with advanced unresectable or metastatic pancreatic adenocarcinoma of the basal-like subtype as defined by PurIST, as well as provide a preliminary assessment of treatment response in basal-like subjects. This study will also follow a subset of subjects with classical subtypes that are treated per standard of care on oxaliplatin-based triplet chemotherapy.

Start Date01 Mar 2025

Sponsor / Collaborator

UNC Lineberger Comprehensive Cancer Center

100 Clinical Results associated with Erlotinib Hydrochloride

100 Translational Medicine associated with Erlotinib Hydrochloride

100 Patents (Medical) associated with Erlotinib Hydrochloride

7,741

Literatures (Medical) associated with Erlotinib Hydrochloride

06 Jan 2025·Cancer Prevention Research

Phase II Clinical Chemoprevention Trial of Weekly Erlotinib before Bladder Cancer Surgery

Article

Author: Messing, Edward ; Scarlett, Cameron O. ; Barroilhet, Lisa ; Lozar, Taja ; Saltzstein, Daniel R. ; Kim, KyungMann ; Huang, Wei ; Ricke, William A. ; House, Margaret ; Schmitz, Natalie S. ; Shore, Neal ; DeShong, Katina ; Downs, Tracy M. ; Havighurst, Thomas C. ; Bailey, Howard H. ; Bivalacqua, Trinity J. ; Wollmer, Barbara ; Parnes, Howard L. ; Twaroski, Kyleigh ; Green, Heather

Abstract:

We performed a clinical trial in patients with non–muscle-invasive (NMI) urothelial cancer randomized (2:1) to the EGFR tyrosine kinase inhibitor erlotinib or placebo (either orally once weekly × 3 doses prior to scheduled surgery) to assess for a difference in EGFR phosphorylation in tumor-adjacent normal urothelium <24 hours post–study dose and tolerance of weekly erlotinib therapy. Thirty-seven volunteers (6 female/31 male; mean age 70; 35 White/2 non-White) with confirmed or suspected NMI urothelial cancer were enrolled into either erlotinib (n = 24; 900 mg-13, 600 mg-11) or placebo (n = 13). IHC assessment of phosphorylated and total EGFR in tumor-adjacent normal urothelium (20 erlotinib and 9 placebo subjects) or tumor (21 erlotinib and 11 placebo subjects) at study end showed no significant difference between those receiving erlotinib or placebo. This was also true for other assessed tissue biomarkers (phosphorylated ERK, ERK, E-cadherin, p53, and Ki67). Adverse events were more common, in a dose-related fashion, in participants receiving erlotinib, e.g., 38% experienced grade 1 with rare grade 2 diarrhea and skin toxicity versus 8% in placebo. Clinically insignificant but statistically significant (P = 0.001) elevations in serum total bilirubin and creatinine were observed in participants receiving erlotinib. Serum erlotinib and metabolite concentrations (OSI-420) confirmed compliance in all subjects receiving erlotinib and did not significantly differ between the 600 and 900 mg doses. Despite compelling preclinical and clinical data for targeted EGFR inhibition in bladder cancer prevention, these data do not support the use of weekly erlotinib therapy to prevent progression of NMI bladder cancer.Prevention Relevance: We evaluated the potential of erlotinib in preventing cancer by performing a randomized, double-blind, placebo-controlled trial of weekly erlotinib therapy in participants undergoing surgical removal of suspected noninvasive bladder neoplasia. Weekly erlotinib therapy was tolerated with common grade 1 to 2 toxicities but without evidence of beneficial effect upon urothelial tissue.See related Spotlight, p. 7

06 Jan 2025·Cancer Prevention Research

Passing the Torch forward: Moving beyond EGFR Inhibition in NMIBC Prevention

Article

Author: Lin, Chia-Chi ; Wu, Tsung-Che

Abstract:

The study by Downs and colleagues targets patients with non–muscle-invasive bladder cancer (NMIBC) to explore secondary/tertiary cancer prevention strategies. Utilizing a “window-of-opportunity” design, erlotinib was evaluated for its effect on EGFR phosphorylation, although the unconventional dosing regimen failed to demonstrate efficacy. New opportunities in NMIBC prevention include targeting FGFR3 mutations with emerging FGFR inhibitors. A future trial design could focus on clinical outcomes such as tumor response and NMIBC recurrence while also evaluating FGFR3 inhibition in both tumor and adjacent normal bladder epithelia.See related article by Downs et al., p. 31

03 Jan 2025·Cancer diagnosis & prognosis

Association of Pretreatment Albumin-bilirubin Grade With Hepatotoxicity and Efficacy in EGFR-TKIs Therapy for NSCLC

Article

Author: Hayakawa, Yuji ; Nagamatsu, Hidetsugu ; Mase, Hiroki ; Araya, Tomoyuki ; Arihara, Hiroki ; Kita, Toshiyuki

Background/Aim: The albumin-bilirubin (ALBI) grade is an assessment tool for hepatic function and prognosis in patients with hepatocellular carcinoma (HCC). However, its significance in patients with non-small cell lung cancer (NSCLC) treated with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) remains unclear. We retrospectively investigated the relationship between pre-treatment ALBI grade and hepatotoxicity and treatment efficacy in patients with NSCLC receiving EGFR-TKIs. Patients and Methods: We analyzed data from 182 patients with NSCLC treated with EGFR-TKIs. Patients were categorized into ALBI grades 1/2a and 2b/3 groups. We examined the association between ALBI grade, hepatotoxicity, and time to treatment failure (TTF) using univariate and multivariate analyses. Results: In the univariate Kaplan-Meier analysis, ALBI grade was not associated with hepatotoxicity (log-rank p=0.56). This finding was consistent with the multivariate analysis of patients treated with gefitinib and erlotinib (n=158). However, In the univariate Kaplan-Meier analysis, the median TTF for the ALBI grade 1/2a group was 10.6 months, compared to 5.8 months for the ALBI grade 2b/3 group (hazard ratio=1.66, 95% confidence interval=1.19-2.33, p=0.003). Multivariate analysis confirmed that ALBI grade 2b/3 (hazard ratio=1.64, 95% confidence interval=1.16-2.30, p<0.01) was independently associated with shortened TTF. Conclusion: Pretreatment ALBI grade classification can predict efficacy in patients with NSCLC treated with EGFR-TKIs.

110

News (Medical) associated with Erlotinib Hydrochloride

07 Jan 2025

·www.prnewswire.com

RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) show statistically significant and clinically meaningful improvement in overall survival versus osimertinib

Median overall survival improvement expected to exceed one year First and only regimen with a survival benefit over current standard of care in first-line treatment of EGFR-mutated lung cancer RARITAN, N.J., Jan. 7, 2025 /PRNewswire/ -- Johnson & Johnson (NYSE:JNJ) today announced positive topline results for the gold standard endpoint in cancer treatment of overall survival (OS) from the Phase 3 MARIPOSA study, evaluating RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) as a first-line therapy for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations. The chemotherapy-free combination regimen met the final pre-specified secondary endpoint of OS and demonstrated clinically meaningful and statistically significant improvement in OS versus the current standard of care osimertinib. Improvement in median OS is expected to exceed one year. Unlike progression-free survival (PFS), which tracks the time a treatment keeps a patient's cancer from progressing, OS helps patients understand the impact therapy could have on the ability to live longer from the start of treatment. Extending life expectancy is the most meaningful indicator of a treatment's impact. "The combination of these two agents previously demonstrated an improvement in progression-free survival, but this does not always capture the impact on the entire treatment course. Evaluation of overall survival can better demonstrate the benefit of a first-line treatment regimen," said Stephen Liu, M.D.*, Associate Professor of Medicine at Georgetown University School of Medicine and Director of Thoracic Oncology and Head of Developmental Therapeutics at Georgetown's Lombardi Comprehensive Cancer Center. "Seeing this increase in overall survival in a trial with mature data is powerful and reaffirms that first-line treatment with RYBREVANT and LAZCLUZE can lead to better patient outcomes." "Every milestone in clinical trials and every approval of a new drug or regimen brings hope and progress for EGFR-positive patients and their families," said Marcia Horn**, President of International Cancer Advocacy Network. "These topline data from the MARIPOSA trial offer renewed optimism in the journey to extend life for EGFR-mutated patients, adding another important option for patients and oncologists." "These new findings reinforce the clinically meaningful impact this chemotherapy-free regimen can have for patients worldwide with non-small cell lung cancer and represent the first overall survival benefit over the current standard of care," said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson Innovative Medicine. "With less than 20 percent of patients living beyond five years, an incredible unmet need remains for EGFR-positive lung cancer. These MARIPOSA results show RYBREVANT plus LAZCLUZE can extend survival beyond the current standard of care, providing patients with more time and hope in their fight against this devastating disease. Extending median overall survival by more than a year could be transformative for these patients." Results from the final OS analysis build upon previously reported data from the interim analysis and positive results from the PFS analysis. MARIPOSA, which enrolled 1,074 patients, is a randomized, Phase 3 study evaluating RYBREVANT® in combination with LAZCLUZE™ versus osimertinib as a first-line treatment of patients with EGFR-mutated NSCLC. The study's primary endpoint was PFS (using RECIST v1.1 guidelines***) as assessed by blinded independent central review (BICR). Secondary endpoints included OS, objective response rate (ORR), duration of response (DOR), second progression-free survival (PFS2) and intracranial PFS. The safety profile of RYBREVANT® plus LAZCLUZE™ was generally consistent with the profiles of the individual treatments. Adverse event rates were consistent in this arm as compared to other RYBREVANT® regimens. Venous thromboembolic events were observed with the combination. Subsequent studies showed that administering oral anticoagulant medicines prophylactically during the initial four months of the RYBREVANT® and LAZCLUZE™ regimen significantly reduced the risk of thrombosis. Due to the impact of these data on patient care, these OS results will be presented at an upcoming major medical meeting, and will be shared with global health authorities. RYBREVANT® combined with LAZCLUZE™ is approved in the United States and Europe for the first-line treatment of patients with EGFR-mutated NSCLC based on the MARIPOSA Phase 3 study. About RYBREVANT® RYBREVANT® (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, is approved in the U.S., Europe and other markets around the world as monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.1 RYBREVANT® is approved in the U.S., Europe and other markets around the world in combination with chemotherapy (carboplatin and pemetrexed) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test. RYBREVANT® is approved in the U.S. and Europe in combination with LAZCLUZE™ (lazertinib) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, as detected by an FDA-approved test. RYBREVANT® is approved in the U.S., Europe and other markets around the world in combination with chemotherapy (carboplatin and pemetrexed) for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitors (TKI). The National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC§ prefer next-generation sequencing–based strategies over polymerase chain reaction–based approaches for the detection of EGFR exon 20 insertion variants. The NCCN Guidelines include: Amivantamab-vmjw (RYBREVANT®) plus lazertinib (LAZCLUZE™) as a Category 1 recommendation for first-line therapy in patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations.2†‡ Amivantamab-vmjw (RYBREVANT®) plus chemotherapy as a Category 1 recommendation for patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations who experienced disease progression after treatment with osimertinib.2†‡ Amivantamab-vmjw (RYBREVANT®) plus chemotherapy as a Category 1 recommendation for first-line therapy in treatment-naive patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion mutation-positive advanced NSCLC.2†‡ Amivantamab-vmjw (RYBREVANT®) as a Category 2A recommendation for patients that have progressed on or after platinum-based chemotherapy with or without an immunotherapy and have EGFR exon 20 insertion mutation-positive NSCLC.2†‡ For more information, visit: . About LAZCLUZE ™ In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of LAZCLUZE™ (marketed as LACLAZA in Korea). LAZCLUZE™ is an oral, third-generation, brain-penetrant EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild-type EGFR. An analysis of the efficacy and safety of LAZCLUZE™ from the Phase 3 LASER301 study was published in The Journal of Clinical Oncology in 2023. About Non-Small Cell Lung Cancer Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 percent of all lung cancer cases.3,4 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.5 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.6 EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients.5,6,7,8,9,10 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.11 The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent.12,13 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation.14 Patients with EGFR exon 20 insertion mutations have a real-world five-year overall survival (OS) of eight percent in the frontline setting, which is worse than patients with EGFR ex19del or L858R mutations, who have a real-world five-year OS of 19 percent.15 IMPORTANT SAFETY INFORMATION1,16 Before you receive RYBREVANT® as a single agent or in combination, tell your healthcare provider about all of your medical conditions, including if you: have a history of lung or breathing problems. are pregnant or plan to become pregnant. RYBREVANT® and LAZCLUZE™ can harm your unborn baby. Females who are able to become pregnant: Your healthcare provider should do a pregnancy test before you start treatment with RYBREVANT® or RYBREVANT® in combination with LAZCLUZE™. You should use effective birth control (contraception) during treatment and for 3 months after your final dose of RYBREVANT®. For patients receiving LAZCLUZE™: You should use effective birth control (contraception) during treatment and for 3 weeks after your last dose of LAZCLUZE™. Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RYBREVANT® or LAZCLUZE™. Males who have female partners who are able to become pregnant: You should use effective birth control during treatment and for 3 weeks after your last dose of LAZCLUZE™. are breastfeeding or plan to breastfeed. It is not known if RYBREVANT® passes into your breast milk. Do not breastfeed during treatment and for 3 months after your last dose of RYBREVANT®. It is not known if LAZCLUZE™ passes into your breast milk. Do not breastfeed during treatment and for 3 weeks after your last dose of LAZCLUZE™. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. LAZCLUZE™ may affect the way other medicines work, and other medicines may affect how LAZCLUZE™ works. You should not start or stop any medicine before you talk with your healthcare provider that prescribed LAZCLUZE™. How will I receive RYBREVANT®? RYBREVANT® will be given to you by your healthcare provider by intravenous infusion into your vein. Your healthcare provider will decide the time between doses as well as how many treatments you will receive. Your healthcare provider will give you medicines before each dose of RYBREVANT® to help reduce the risk of infusion-related reactions. RYBREVANT® may be given in combination with the medicines carboplatin and pemetrexed. If you have any questions about these medicines, ask your healthcare provider. If your treatment with RYBREVANT® is given in combination with LAZCLUZE™ (lazertinib), you should take your dose of LAZCLUZE™ by mouth anytime before your infusion with RYBREVANT®. If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. How should I take LAZCLUZE™? Take LAZCLUZE™ exactly as your healthcare provider tells you to take it. Take LAZCLUZE™ one (1) time each day. On the day RYBREVANT® is also given, take LAZCLUZE™ anytime before receiving the RYBREVANT® infusion. You can take LAZCLUZE™ with or without food. Swallow LAZCLUZE™ tablets whole. Do not crush, cut, or chew the tablets. If you miss a dose of LAZCLUZE™ and: it has been less than 12 hours, take the missed dose. it has been more than 12 hours, skip the dose and take your next dose at your regularly scheduled time. If you vomit a dose of LAZCLUZE™, do not take an extra dose. Take your next dose at your regularly scheduled time. LAZCLUZE™ may be given in combination with other anti-cancer medicines. If you have any questions about these medicines, ask your healthcare provider. What should I avoid while receiving RYBREVANT® and/or LAZCLUZE™? RYBREVANT® and RYBREVANT® in combination with LAZCLUZE™ can cause skin reactions. You should limit your time in the sun during and for 2 months after your treatment with RYBREVANT® and/or LAZCLUZE™. Wear protective clothing and use sunscreen during treatment with RYBREVANT® and/or LAZCLUZE™. What are the possible side effects of RYBREVANT® or LAZCLUZE™? RYBREVANT® and LAZCLUZE™ may cause serious side effects, including: infusion-related reactions. Infusion-related reactions are common with RYBREVANT® and can be severe or serious. Tell your healthcare provider right away if you get any of the following symptoms during your infusion of RYBREVANT®: lung problems. RYBREVANT® may cause lung problems that may lead to death. LAZCLUZE™ may also cause lung problems that may lead to death. Symptoms may be similar to those symptoms from lung cancer. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including shortness of breath, cough, or fever. blood clot problems. Blood clots are a serious, but common side effect of RYBREVANT®, when given together with LAZCLUZE™, may cause blood clots in the veins of your legs (deep vein thrombosis) or lungs (pulmonary embolism) that may lead to death. Your healthcare provider will start you on medicine to prevent blood clots for the first 4 months of treatment. Tell your healthcare provider right away if you have any signs and symptoms of blood clots, including swelling, pain or tenderness in the leg, sudden unexplained chest pain, or shortness of breath. skin problems. RYBREVANT® can cause severe rash; including blisters, peeling, skin pain and sores, redness, raised acne-like bumps, itching, and dry skin. LAZCLUZE™ may cause severe rash including redness, raised acne-like bumps, itching, and dry skin. You may use alcohol-free (isopropanol-free, ethanol-free) moisturizing cream to reduce the risk of skin problems. Tell your healthcare provider right away if you get any skin reactions. Your healthcare provider may treat you with a medicine(s) or send you to see a skin specialist (dermatologist) if you get skin reactions during treatment with RYBREVANT® or LAZCLUZE™. See "What should I avoid while receiving RYBREVANT® and/or LAZCLUZE™?" eye problems. RYBREVANT® may cause eye problems. LAZCLUZE™ may also cause eye problems. Tell your healthcare provider right away if you get symptoms of eye problems which may include: Your healthcare provider may send you to see an eye specialist (ophthalmologist) if you get new or worsening eye problems during treatment with RYBREVANT® or LAZCLUZE™. You should not use contact lenses until your eye symptoms are checked by a healthcare provider. The most common side effects of RYBREVANT® in combination with LAZCLUZE™ (lazertinib) include: The most common side effects of RYBREVANT® when given in combination with carboplatin and pemetrexed include: The most common side effects of RYBREVANT® when given alone: LAZCLUZE™ may cause fertility problems in males and females, which may affect your ability to have children. Talk to your healthcare provider if this is a concern for you. Your healthcare provider may temporarily stop, decrease your dose, or completely stop your treatment with RYBREVANT® or LAZCLUZE™ if you have serious side effects. These are not all of the possible side effects of RYBREVANT® or LAZCLUZE™. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. General information about the safe and effective use of RYBREVANT®: Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your healthcare provider or pharmacist for information about RYBREVANT® that is written for health professionals. General information about the safe and effective use of LAZCLUZE™: Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use LAZCLUZE™ for a condition for which it was not prescribed. Do not give LAZCLUZE™ to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about LAZCLUZE™ that is written for health professionals. Please read full Prescribing Information for RYBREVANT®. Please read full Prescribing Information for LAZCLUZE™. About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at or at . Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC, and Janssen Biotech, Inc., are Johnson & Johnson companies. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of RYBREVANT® (amivantamab-vmjw) and LAZCLUZE™ (lazertinib). The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc. and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc. nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. *Dr. Liu has served as a consultant to J&J; he has not been paid for any media work. **Marcia Horn has not been paid for any media work. ***RECIST (version 1.1) refers to Response Evaluation Criteria in Solid Tumors, which is a standard way to measure how well solid tumors respond to treatment and is based on whether tumors shrink, stay the same or get bigger. †See the NCCN Guidelines for detailed recommendations, including other treatment options. ‡The NCCN Guidelines for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories. §The NCCN Content does not constitute medical advice and should not be used in place of seeking professional medical advice, diagnosis or treatment by licensed practitioners. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. Source: Johnson & Johnson 1 RYBREVANT® Prescribing Information. Horsham, PA: Janssen Biotech, Inc. 2 Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.9.2024 © National Comprehensive Cancer Network, Inc. All rights reserved. To view the most recent and complete version of the guideline, go online to NCCN.org. Accessed December 2024. 3 The World Health Organization. Cancer. . Accessed December 2024. 4 American Cancer Society. What is Lung Cancer? . Accessed December 2024. 5 Oxnard JR, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013 Feb;8(2):179-84. doi: 10.1097/JTO.0b013e3182779d18. 6 Bauml JM, et al. Underdiagnosis of EGFR Exon 20 Insertion Mutation Variants: Estimates from NGS-based Real World Datasets. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore. 7 Pennell NA, et al. A phase II trial of adjuvant erlotinib in patients with resected epidermal growth factor receptor-mutant non-small cell lung cancer. J Clin Oncol. 37:97-104. 8 Burnett H, et al. Epidemiological and clinical burden of EGFR exon 20 insertion in advanced non-small cell lung cancer: a systematic literature review. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore. 9 Zhang YL, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48):78985-78993. 10 Midha A, et al. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity. Am J Cancer Res. 2015;5(9):2892-2911. 11 American Lung Association. EGFR and Lung Cancer. . Accessed December 2024. 12 Howlader N, et al. SEER Cancer Statistics Review, 1975-2016, National Cancer Institute. Bethesda, MD, , based on November 2018 SEER data submission, posted to the SEER web site. 13 Lin JJ, et al. Five-year survival in EGFR-mutant metastatic lung adenocarcinoma treated with EGFR-TKIs. J Thorac Oncol. 2016 Apr;11(4):556-65. 14 Arcila, M. et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013 Feb; 12(2):220-9. 15 Girard N, et al. Comparative clinical outcomes for patients with NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore. 16 LAZCLUZE™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc. SOURCE Johnson & Johnson WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultPhase 3Drug ApprovalLicense out/in

30 Dec 2024

·pipelinereview.com

European Commission approves RYBREVANT®▼ (amivantamab) in combination with LAZCLUZE®▼ (lazertinib) for the first-line treatment of patients with EGFR-mutated advanced non-small cell lung cancer

This multitargeted, chemotherapy-free combination demonstrated superiority over osimertinib monotherapy for the first-line treatment of patients with EGFR-mutated NSCLC 1 In the Phase 3 MARIPOSA study, amivantamab plus lazertinib significantly reduced the risk of disease progression or death by 30 percent versus osimertinib monotherapy 1 BEERSE, Belgium I Decemer 30, 2024 I Janssen-Cilag International NV, a Johnson & Johnson company, today announced that the European Commission (EC) has approved a Type II variation extension of indication for RYBREVANT ® ▼ (amivantamab), in combination with LAZCLUZE ® ▼ (lazertinib), for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or exon 21 L858R substitution mutations. “For people living with advanced NSCLC harbouring EGFR mutations, new treatment options are urgently needed in the first-line setting,” said Enriqueta Felip, M.D., Ph.D, head of the thoracic cancer unit at Vall d’Hebron University Hospital, Barcelona, Spain*. “The amivantamab and lazertinib combination has shown significant progression-free survival improvements in patients with previously untreated EGFR-mutated advanced NSCLC, including those with brain metastases, compared to osimertinib monotherapy. This approval by the European Commission offers the potential to broaden first-line treatment options and provide a new standard of care for eligible patients.” Lung cancer is Europe’s biggest cancer killer, with NSCLC accounting for 85 percent of all lung cancer cases. 2,3 EGFR mutation-positive NSCLC refers to a subtype of lung cancer based on specific mutations in the EGFR gene. 4 While there are different types of EGFR mutations, EGFR ex19del and EGFR exon 21 L858R are the most common, accounting for approximately 85-90 percent of mutations. 4 Patients are often treated with targeted therapies known as EGFR tyrosine kinase inhibitors (TKIs). 5 However, treatment resistance or disease reoccurrence remains a significant challenge and there is an urgent need for alternative, novel targeted therapies earlier in the treatment pathway to address resistance and improve survival outcomes. 6,7 “This approval marks significant progress for those living with the devastating impact of EGFR-mutated non-small cell lung cancer, who too often face a poor prognosis and limited treatment options,” said Henar Hevia, Ph.D., Senior Director, EMEA Therapeutic Area Lead, Oncology. “The combination of amivantamab and lazertinib exemplifies the potential of targeted precision medicine, offering a tailored approach that addresses the underlying genetic drivers of the disease, and avoids or delays the need for chemotherapy.” The EC approval is supported by results from the Phase 3 MARIPOSA ( NCT04487080 ) study, evaluating amivantamab in combination with lazertinib compared to osimertinib as first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or exon 21 L858R substitution mutations. 1 The study, which was featured during a Presidential Symposium session at the 2023 European Society of Medical Oncology (ESMO) Congress, met its primary endpoint of progression-free survival (PFS), and at median follow-up of 22 months, amivantamab plus lazertinib reduced the risk of disease progression or death by 30 percent compared to osimertinib (median PFS: 23.7 months versus 16.6 months; hazard ratio [HR]=0.70; 95 percent confidence interval [CI], 0.58–0.85; P <0.001) as assessed by blinded independent central review (BICR). 1 The median duration of response (DOR) was longer for patients receiving amivantamab plus lazertinib compared to osimertinib, with a nine-month improvement in median DOR (25.8 vs. 16.8 months). 1 The safety profile of the combination of amivantamab and lazertinib was consistent with previous reports from Phase 1-2 studies, with mostly Grade 1 or 2 adverse events (AEs). 1 Toxicity was largely manageable with dose interruptions and reductions, along with supportive care measures commonly used in the treatment of patients with NSCLC. 1 The most common treatment emergent adverse events (TEAEs) of any grade were paronychia (68 percent), infusion-related reactions (63 percent), and rash (62 percent). 1 Amivantamab plus lazertinib had higher rates of EGFR- and MET-related AEs and venous thromboembolism compared to osimertinib, except diarrhoea, for which rates were higher for osimertinib. 1 The commonest grade 3 or higher TEAEs were rash (15 percent), paronychia (11 percent) and dermatitis acneiform (8 percent). 1 The rate of discontinuation of all study treatments due to treatment-related AEs for the amivantamab combination was 10 percent. 1 The rate of interstitial lung disease (including pneumonitis) was less than three percent in both arms. 1 An EC decision on a Marketing Authorisation (MA) for lazertinib for the corresponding combination regimen indication is pending, following a Committee for Medicinal Products for Human Use (CHMP) positive opinion last month. 8 – ENDS – Notes to editors About the MARIPOSA Study MARIPOSA ( NCT04487080 ), which enrolled 1,074 patients, is a randomised, Phase 3 study evaluating amivantamab in combination with lazertinib versus osimertinib and versus lazertinib alone in first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or exon 21 L858R substitution mutations. 1 The primary endpoint of the study is PFS (using RECIST v1.1 guidelines ‡ ) as assessed by BICR. 1 Secondary endpoints include overall survival (OS), overall response rate (ORR), duration of response (DOR), second progression free survival (PFS2) and intracranial PFS. 1 The MARIPOSA study required all patients to have serial brain imaging with magnetic resonance imaging (MRI), which is important for a disease where almost 30 percent of patients develop brain metastases. 1,9 The primary endpoint of PFS in MARIPOSA included these central nervous system (CNS) events detected by serial brain MRIs. 1 The median PFS when censoring CNS-only first progressions was 27.5 months for the combination of amivantamab and lazertinib, compared to 18.5 months for osimertinib (HR=0.68; 95 percent CI, 0.56–0.83; P <0.001**). 1 Extracranial PFS, which may more closely approximate what would be seen in other trials, was also explored in MARIPOSA. 1 Longer-term follow-up data presented at the International Association for the Study of Lung Cancer (IASLC) 2024 World Conference on Lung Cancer (WCLC) demonstrated a strong favourable overall survival (OS) trend for amivantamab plus lazertinib versus Osimertinib. At three years (median follow-up of 31.1 months), 61 percent of patients receiving amivantamab plus lazertinib were alive compared to 53 percent of those treated with osimertinib based on an analysis performed at the request of a health authority*** (median OS not estimable [NE] vs 37.3 months; HR=0.77; 95 percent CI, 0.61-0.96; nominal P =0.019). 10 About Amivantamab Amivantamab is a fully-human EGFR-MET bispecific antibody that acts by targeting tumours with activating and resistance EGFR mutations and MET mutations and amplifications, and by harnessing the immune system. 11,12,13,14 The European Commission (EC) has granted marketing authorisation of amivantamab in the following indications: 15 In May 2024, an application for the extension of the amivantamab marketing authorisation was submitted seeking approval for the use of a subcutaneous (SC) formulation of amivantamab in combination with lazertinib for the first-line treatment of adult patients with advanced NSCLC with EGFR ex19del or L858R mutations, and for the use of SC amivantamab monotherapy in adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy. 16 For a full list of adverse events and information on dosage and administration, contraindications and other precautions when using amivantamab, please refer to the Summary of Product Characteristics . 15 ▼ In line with EMA regulations for new medicines, amivantamab is subject to additional monitoring. About Lazertinib In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib. Lazertinib is an oral, third-generation, brain-penetrant EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild-type EGFR. 17 An analysis of the efficacy and safety of lazertinib from the Phase 3 study LASER301 was published in The Journal of Clinical Oncology in 2023. 17 ▼ In line with EMA regulations for new medicines, lazertinib is subject to additional monitoring. About Non-Small Cell Lung Cancer In Europe, it is estimated that 484,306 people were diagnosed with lung cancer in 2022. 2 NSCLC accounts for 85 percent of all lung cancer cases. 3 Lung cancer is Europe’s biggest cancer killer, with more deaths than breast cancer and prostate cancer combined. 2 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma. 3 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division. 3,18 EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients. 19,20,21,22 EGFR ex19del or EGFR exon 21 L858R mutations are the most common EGFR mutations. 23 The five-year survival rate for patients with advanced NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent and between 25-32 percent of patients receiving the current first-line standard of care, osimertinib, do not survive long enough to reach second-line treatment. 24,25,26 About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://innovativemedicine.jnj.com/emea/ . Follow us at http://www.linkedin.com/company/jnj-innovative-medicine-emea . Janssen-Cilag International NV, Janssen Research & Development, LLC, Janssen Biotech, Inc. and Janssen-Cilag, S.A. are Johnson & Johnson companies. * Prof. Felip has served as a consultant to Janssen-Cilag International NV; she has not been paid for any media work. ** Nominal P -value; endpoint was exploratory and not part of hierarchical hypothesis testing. *** This analysis was requested by health authorities and had nominal alpha spend. A P-value of ≤0.00001 was required for statistical significance. ‡ RECIST (version 1.1) refers to Response Evaluation Criteria in Solid Tumors, which is a standard way to measure how well solid tumours respond to treatment and is based on whether tumours shrink, stay the same or get bigger. 1 Cho BC, et al. Amivantamab Plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC. The New England Journal of Medicine 2024. doi:10.1056/NEJMoa2403614. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2403614 . Accessed December 2024. 2 Global Cancer Observatory. Cancer Today. Available at: https://gco.iarc.who.int/media/globocan/factsheets/populations/908-europe-fact-sheet.pdf . Accessed December 2024. 3 Zappa C, et al. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res . 2016;5(3):288–300. 4 Batra U, et al . Differential clinicopathological features, treatments and outcomes in patients with Exon 19 deletion and Exon 21 L858R EGFR mutation-positive adenocarcinoma non-small-cell lung cancer. BMJ Open Respir Res. 2023 Jun;10(1). 5 Johnson M, et al . Treatment strategies and outcomes for patients with EGFR-mutant non-small cell lung cancer resistant to EGFR tyrosine kinase inhibitors: Focus on novel therapies. Lung Cancer. 2022 Aug;170:41-51. 6 Pecci F, et al . Non-small-cell lung cancer: how to manage EGFR-mutated disease. Drugs Context. 2022;11:2022-4-1. 7 Fu, K, et al . Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance. J Hematol Oncol. 15, 173 (2022). https://doi.org/10.1186/s13045-022-01391-4. 8 Innovativemedicine.jnj.com/EMEA. RYBREVANT®▼ (amivantamab) in combination with LAZCLUZE®▼ (lazertinib) for the first-line treatment of patients with EGFR-mutated advanced non-small cell lung cancer. Available at: https://innovativemedicine.jnj.com/emea/chmp-recommends-rybrevant-amivantamab-in-combination-with-lazcluze-lazertinib-for-the-first-line-treatment-of-patients-with-egfr-mutated-advanced-non-small-cell-lung-cancer . Accessed December 2024 9 Fuchs J, et al. Resection of isolated brain metastases in non-small cell lung cancer (NSCLC) patients – evaluation of outcome and prognostic factors: A retrospective multicenter study. PLoS ONE. 16(6):e0253601. https://doi.org/10.1371/journal.pone.0253601 . 10 Gadgeel SM, et al. Amivantamab Plus Lazertinib vs Osimertinib in First-line EGFR-mutant Advanced NSCLC: Longer Follow-up of the MARIPOSA Study. IASLC WCLC 2024. September 8, 2024. 11 Grugan KD, et al. Fc-mediated activity of EGFR x c-Met bispecific antibody JNJ-61186372 enhanced killing of lung cancer cells. MAbs . 2017;9(1):114-126. 12 Moores SL, et al. A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor-Resistant Lung Tumors. Cancer Res . 2016;76(13)(suppl 27216193):3942-3953. 13 Yun J, et al. Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR–MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion–Driven NSCLC. Cancer Discov . 2020;10(8):1194-1209. 14 Vijayaraghavan S, et al. Amivantamab (JNJ-61186372), an Fc Enhanced EGFR/cMet Bispecific Antibody, Induces Receptor Downmodulation and Antitumor Activity by Monocyte/Macrophage Trogocytosis. Mol Cancer Ther . 2020;19(10):2044-2056. 15 European Medicines Agency. Amivantamab Summary of Product Characteristics. August 2024. Available at https://www.ema.europa.eu/en/documents/product-information/rybrevant-epar-product-information_en.pdf . Accessed December 2024. 16 Innovativemedicine.jnj.com/EMEA. Johnson & Johnson submits application to the European Medicines Agency seeking approval of subcutaneous formulation of RYBREVANT ® ▼ (amivantamab) for the treatment of patients with EGFR-mutated non-small cell lung cancer. Available at: https://innovativemedicine.jnj.com/emea/newsroom/oncology/johnson-johnson-submits-application-to-the-european-medicines-agency-seeking-approval-of-subcutaneous-formulation-of-rybrevant-amivantamab-for-the-treatment-of-patients-with-egfr-mutated-non-small-cell-lung-cancer . Accessed December 2024. 17 Cho, BC, et al. Lazertinib versus gefitinib as first-line treatment in patients with EGFR -mutated advanced non-small-cell lung cancer: Results From LASER301. J Clin Oncol . 2023;41(26):4208-4217. 18 Wee P & Wang Z. Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers . 2017;9(12):52. 19 Pennell NA, et al. A phase II trial of adjuvant erlotinib in patients with resected epidermal growth factor receptor-mutant non-small cell lung cancer. J Clin Oncol . 2019;37(2):97-104. 20 Burnett H, et al. Epidemiological and clinical burden of EGFR exon 20 insertion in advanced non-small cell lung cancer: a systematic literature review. Abstract presented at: World Conference on Lung Cancer Annual Meeting (Singapore); January 29, 2021. 21 Zhang YL, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget . 2016;7(48):78985- 78993. 22 Midha A, et al. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity. Am J Cancer Res . 2015;5(9):2892-2911. 23 American Lung Association. EGFR and Lung Cancer. Available at: https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptomsdiagnosis/biomarker-testing/egfr . Accessed December 2024. 24 Lin JJ, et al. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs. J Thorac Oncol . 2016;11(4):556-65. 25 Nieva J, et al. A real-world (rw) observational study of long-term survival (LTS) and treatment patterns after first-line (1L) osimertinib in patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive (m) advanced non-small cell lung cancer (NSCLC). Ann Oncol . 2023;34, S774. 26 Girard N, et al. Mortality among EGFR-mutated advanced NSCLC patients after frontline osimertinib treatment: A real-world, US attrition analysis. J Thorac Oncol. 2023;18(4), S51-52. SOURCE: Janssen

Clinical ResultPhase 3License out/inDrug ApprovalASCO

15 Nov 2024

·www.globenewswire.com

Sol-Gel Reports Third Quarter 2024 Financial Results and Provides Corporate Updates

Mori Arkin's appointment as interim CEO as of January 1, 2025 approved by shareholdersPhase 3 clinical trial of SGT-610 for Gorlin Syndrome is ongoing with over 40 clinical sites activatedSGT-210 proof-of-concept study in patients suffering from Darier disease is ongoing NESS ZIONA, Israel, Nov. 15, 2024 (GLOBE NEWSWIRE) -- Sol-Gel Technologies, Ltd. (NASDAQ: SLGL), a dermatology company, pioneering treatments for patients with severe skin conditions, conducting a Phase-3 clinical trial of SGT-610 (patidegib gel, 2%) for Gorlin syndrome, and with two approved large-category dermatology products, TWYNEO® and EPSOLAY®, today announced financial results for the third quarter ended September 30, 2024, and provided a corporate update. Q3 2024 and Recent Corporate Developments On November 4, 2024, Sol-Gel's shareholders approved the appointment of our Chairman, Mr. Mori Arkin, as Interim CEO as of January 1, 2025. Mr. Arkin will replace Sol-Gel's founder and current CEO, Dr. Alon Seri-Levy, who will remain as a consultant to the Company for a period of at least one year.On November 13, 2024, Sol-Gel received approval from Nasdaq to transfer the listing of its Ordinary Shares from The Nasdaq Global Market to The Nasdaq Capital Market. The transfer became effective as of November 15, 2024. This transfer has been requested in order to be provided with a second 180-day compliance period to regain compliance with The Nasdaq Stock Market LLC’s ("Nasdaq") minimum bid price rule. Sol-Gel’s Ordinary Shares will continue to trade under the symbol “SLGL” and trading of its Ordinary Shares will not be affected by this transfer. The Nasdaq Capital Market is a continuous trading market that operates in substantially the same manner as The Nasdaq Global Market. The approval of the second compliance period and the transfer to the Nasdaq Capital Market are expected based upon the Company meeting all other applicable requirements for initial listing on the Capital Market, except for the bid price requirement, the Company’s written notice of its intention to cure the deficiency by effecting a reverse stock split, if necessary, and additional supporting information provided in its application.On August 15, 2024, Sol-Gel signed a new agreement with Padagis, which replaced the parties’ prior collaboration agreement for the development and commercialization of a generic drug product to Zoryve® Cream (roflumilast cream 0.3%). Under this new agreement, Sol-Gel is to unconditionally receive eight quarterly payments which will be paid over 24 months and low single digit royalties from gross profits from sales of roflumilast cream for a period of five years, in lieu of its 50% share in future gross profits from such sales. In addition, Sol-Gel will cease paying any outstanding and future costs related to this prior collaboration agreement. The amount to be received from Padagis, together with the elimination of future expected expenses related to this asset, is expected to enhance Sol-Gel's cash position by approximately $6 million.On September 27, 2024, Sol-Gel signed an additional license agreement for the commercialization of Twyneo and Epsolay in South Korea. This Agreement is in addition to the six agreements Sol-Gel signed during July 2024 in various territories covering most of European countries and South Africa. These already signed agreements, together with agreements we anticipate to sign in the future covering Latin American countries, Australia, New Zealand, Spain, Italy and Portugal, are expected to provide upfront and regulatory milestone payments of up to $3.7 million, which Sol-Gel expects to utilize on adapting TWYNEO and EPSOLAY to the regulatory requirements of these new territories. Based on the forecasts received from Sol-Gel’s current and potential partners, Sol-Gel expects that TWYNEO and EPSOLAY will launch in the majority of these new territories in 2027 and 2026 respectively, and following launch, these transactions are anticipated to provide Sol-Gel with an annual royalty revenue stream starting with approximately $1 million to $2 million in 2026 and growing gradually to approximately up to $10 million for the year 2030 and further. The Phase 3 study in Sol-Gel’s key asset SGT-610 in approximately 140 subjects (with 100 subjects required to complete the Study) at about 40 experienced clinical centers is ongoing. To date, Sol-Gel has signed agreements with 43 centers in multiple countries, including the U.S., Spain, The Netherlands, Germany, Italy, France and the UK, and approximately 40 of these centers have been activated. Top line results are anticipated in H2 2026. SGT-610 is a topically applied patidegib, a hedgehog signaling pathway blocker 2% gel If approved, SGT-610 is expected to be the first approved product for the prevention of new BCC lesions in Gorlin syndrome patients and is targeting a market exceeding $300 million annually.Sol-Gel’s proof-of-concept study for SGT-210 (topical erlotinib) in patients with Darier disease is ongoing. Darier disease is a significant unmet medical need, with a market potential estimated between $200 to $300 million. If Sol-Gel successfully completes this proof-of-concept study and the required pre-clinical studies, it anticipates filing for a Phase 2 IND in Q2 2025. SGT-210 is currently being used in a compassionate use treatment of a pediatric patient suffering from a rare disease, and given the preliminary highly encouraging response, we are cautiously optimistic about the potential for success in other viable keratoderma indications, recognizing that further research and clinical studies are necessary to validate any broader applications of our therapy. Mr. Mori Arkin, Executive Chairman of Sol-Gel, stated: “The quarterly results reflects our continuous effort to maximize the value of our assets, while exploring business opportunities for non-dilutive funding. We continue to conduct the pivotal Phase 3 clinical trial of SGT-610 as planned and are encouraged by the rate of recruitment of patients. We believe that our approach for preventing new basal cell carcinomas in Gorlin Syndrome patients can ease the suffering of patients and bring cure to an unmet medical need, in a target market that exceeds $300 million. In addition, our proof-of-concept study for SGT-210 (topical erlotinib) in Darier disease patients, targeting a market of between $200 million to $300 million, continues. The Company’s strategy, with our two leading assets, pave the way for further strengthening Sol-Gel's business and competitive position.” Financial Results for the Third Quarter 2024 Total revenue in the third quarter was $5.4 million which primarily consisted of licensing revenue from Padagis, Galderma, Searchlight and seven new license agreements, compared to $0.2 million revenues for the same period in 2023. Research and development expenses were $4.8 million compared to $4.7 million for the same period in 2023. The increase of $0.1 million was primarily attributed to an increase of $0.7 million in clinical trial expenses related to SGT-610, an increase of $0.5 million in expenses related to the commercialization of Epsolay and Twyneo in other territories and an increase of $0.3 million in clinical expenses related to SGT-210, offset by a decrease of $0.4 million in clinical development expenses related to a generic product, a decrease of $0.5 million in payroll expenses due to the adoption of cost saving measures initiated during the third quarter of 2023 and a decrease of $0.5 million related to R&D and Operations expenses due to cost measures savings. General and administrative expenses were $1.4 million compared to $1.9 million for the same period in 2023. The decrease of $0.5 million was mainly attributed to a decrease of $0.4 million in professional expenses and a decrease of $0.1 million in payroll expenses due to the adoption of cost saving measures initiated during the third quarter of 2023. Sol-Gel reported a net loss of $0.4 million for the third quarter of 2024 and loss of $0.01 per basic and diluted share, compared to a net loss of $5.7 million and a loss of $0.21 per basic and diluted share for the same period in 2023. As of September 30, 2024, Sol-Gel had $14.6 million in cash, cash equivalents, and deposits and $14.6 million in marketable securities for a total balance of $29.2 million. The Company expects its cash resources to fund cash requirements into the first quarter of 2026. About TWYNEO and EPSOLAY TWYNEO is a topical cream containing a fixed-dose combination of tretinoin, 0.1%, and benzoyl peroxide, 3%, cream for the treatment of acne vulgaris in adults and pediatric patients 9 years of age and older. TWYNEO is the first acne treatment that contains a fixed-dose combination of benzoyl peroxide and tretinoin. Tretinoin and benzoyl peroxide are widely prescribed separately for acne vulgaris; however, benzoyl peroxide causes degradation of the tretinoin molecule, thereby potentially reducing its effectiveness if used at the same time or combined in the same formulation. TWYNEO uses silica (silicon dioxide) core shell structures to separately micro-encapsulate tretinoin crystals and benzoyl peroxide crystals enabling inclusion of the two active ingredients in the cream. EPSOLAY is a topical cream containing benzoyl peroxide (BPO), 5%, for the treatment of bumps and blemishes (inflammatory lesions) of rosacea in adults. EPSOLAY utilizes a proprietary, patented technology to encapsulate BPO within silica-based microcapsules to create a barrier between the medication and the skin. The silica-based shell is designed to slowly release BPO over time to provide a tolerable and effective treatment. About Gorlin Syndrome and SGT-610 SGT-610, a hedgehog signaling pathway blocker, has the potential to be the first ever treatment for prevention of BCCs in Gorlin syndrome patients, if approved. Gorlin syndrome, an autosomal dominant genetic disorder affecting approximately 1 in 27,000-31,000 people in the U.S., is mostly caused by inheritance of one defective copy of the tumor suppressor patched homolog 1 (PTCH1) gene. Normally, the PTCH1 gene blocks the smoothened, frizzle class receptor (SMO) gene, turning off the hedgehog signaling pathway when it is not needed. Mutations in the PTCH1 gene may cause a loss of PTCH1 function, release of SMO, and may allow BCC tumor cells to divide uncontrollably. Patidegib, the active substance in SGT-610, is designed to block the SMO signal, thus, allowing cells to function normally and reducing the production of new tumors. About Darier Disease and SGT-210 SGT-210 is a topical erlotinib drug candidate that is formulated for the treatment of Darier Disease and other hyperkeratosis-related indications. Erlotinib is a tyrosine kinase receptor inhibitor that acts on the epidermal growth factor receptor, a protein present on cell surfaces that plays a key role in promoting cell growth and division. Darier Disease is a rare, genetic keratinization disorder which is classically characterized scaly crusted papules in a seborrheic distribution and in skin folds. About Sol-Gel Technologies Sol-Gel Technologies, Ltd. is a dermatology company focused on identifying, developing and commercializing or partnering drug products to treat skin diseases. Sol-Gel developed TWYNEO which is approved by the FDA for the treatment of acne vulgaris in adults and pediatric patients nine years of age and older; and EPSOLAY, which is approved by the FDA for the treatment of inflammatory lesions of rosacea in adults. The Company’s pipeline also includes Phase 3 clinical trial of Orphan and breakthrough drug candidate SGT-610, which is a new topical hedgehog inhibitor being developed to prevent the new basal cell carcinoma lesions in patients with Gorlin syndrome that is expected to have an improved safety profile compared to oral hedgehog inhibitors as well as topical drug candidate SGT-210 under investigation for the treatment of rare hyper keratinization disorders. For additional information, please visit our new website: www.sol-gel.com Forward Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, but not limited to the amounts to be received under our current and future licensing agreements and under our agreement with Padagis with respect to the generic drug product to Zoryve® Cream (roflumilast cream, 0.3%), the out-licensing of Twyneo and Epsolay in additional territories, our expected cash runway, the potential of Sol-Gel’s assets including Twyneo, Epsolay, SGT-610, and SGT-210, the timeline for advancing SGT-610 and SGT-210, the size of SGT-610’s and SGT-210 markets and our ability to receive a second 180 days period to regain compliance with the Nasdaq requirement. In some cases, you can identify forward-looking statements by terminology such as “believe,” “may,” “estimate,” “continue,” “anticipate,” “intend,” “should,” “plan,” “expect,” “predict,” “potential,” or the negative of these terms or other similar expressions. Forward-looking statements are based on information we have when those statements are made or our management’s current expectations and are subject to risks and uncertainties that could cause actual performance or results to differ materially from those expressed in or suggested by the forward-looking statements. Important factors that could cause such differences include, but are not limited to, delays in regulatory milestones, such as a delay in the filing for a Phase 2 IND for SGT-210 and a delay in topline results for our SGT-610 clinical trial, our ability to enter into further collaborations, lower than anticipated annual revenue income from new collaborations and a delay in the timing of our clinical trials, the success of our clinical trials, and an increase in our anticipated costs and expenses, as well as the following factors: (i) the adequacy of our financial and other resources, particularly in light of our history of recurring losses and the uncertainty regarding the adequacy of our liquidity to pursue our complete business objectives; (ii) our ability to complete the development of our product candidates; (iii) our ability to find suitable co-development partners; (iv) our ability to obtain and maintain regulatory approvals for our product candidates in our target markets, the potential delay in receiving such regulatory approvals and the possibility of adverse regulatory or legal actions relating to our product candidates even if regulatory approval is obtained; (v) our collaborators’ ability to commercialize our pharmaceutical product candidates; (vi) our ability to obtain and maintain adequate protection of our intellectual property; (vii) our collaborators’ ability to manufacture our product candidates in commercial quantities, at an adequate quality or at an acceptable cost; (viii) our collaborators’ ability to establish adequate sales, marketing and distribution channels; (ix) acceptance of our product candidates by healthcare professionals and patients; (x) the possibility that we may face third-party claims of intellectual property infringement; (xi) the timing and results of clinical trials that we may conduct or that our competitors and others may conduct relating to our or their products; (xii) intense competition in our industry, with competitors having substantially greater financial, technological, research and development, regulatory and clinical, manufacturing, marketing and sales, distribution and personnel resources than we do; (xiii) potential product liability claims; (xiv) potential adverse federal, state and local government regulation in the United States, China, Europe or Israel; and (xv) loss or retirement of key executives and research scientists; (xvi) general market, political and economic conditions in the countries in which the Company operates; and, (xvii) the current war between Israel and Hamas and any deterioration of the war in Israel into a broader regional conflict involving Israel with other parties. These factors and other important factors discussed in the Company's Annual Report on Form 20-F filed with the Securities and Exchange Commission (“SEC”) on March 13, 2024, and our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Except as required by law, we undertake no obligation to update any forward-looking statements in this press release. Sol-Gel Contact:Eyal Ben-OrChief Financial Officerinfo@sol-gel.com+972-8-9313429 CONDENSED CONSOLIDATED BALANCE SHEETS(U.S. dollars in thousands, except share and per share data) December 31,September 30, 2023 2024 A s s e t s CURRENT ASSETS: Cash and cash equivalents$7,513 $13,420 Bank deposits 10,012 - Marketable securities 20,471 14,631 Accounts receivables 377 7,020 Prepaid expenses and other current assets 2,794 2,881 TOTAL CURRENT ASSETS 41,167 37,952 NON-CURRENT ASSETS: Restricted long-term deposits and cash equivalents 1,284 1,285 Property and equipment, net 434 250 Operating lease right-of-use assets 1,721 1,397 Other long-term assets 55 1,542 Funds in respect of employee rights upon retirement 626 554 TOTAL NON-CURRENT ASSETS 4,120 5,028 TOTAL ASSETS$45,287 $42,980 Liabilities and shareholders' equity CURRENT LIABILITIES: Accounts payable$154 $1,519 Other accounts payable 3,921 4,631 Current maturities of operating leases 447 384 TOTAL CURRENT LIABILITIES 4,522 6,534 LONG-TERM LIABILITIES: Operating leases liabilities 1,206 922 Liability for employee rights upon retirement 915 819 TOTAL LONG-TERM LIABILITIES 2,121 1,741 TOTAL LIABILITIES 6,643 8,275 SHAREHOLDERS' EQUITY: Ordinary Shares, NIS 0.1 par value – authorized: 50,000,000 as of December 31, 2023 and September 30, 2024; issued and outstanding: 27,857,620 as of December 31, 2023 and September 30, 2024. 774 774 Additional paid-in capital 258,173 258,968 Accumulated deficit (220,303) (225,037)TOTAL SHAREHOLDERS' EQUITY 38,644 34,705 TOTAL LIABILITIES AND SHAREHOLDERS' EQUITY$45,287 $42,980 SOL-GEL TECHNOLOGIES LTD.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(U.S. dollars in thousands, except share and per share data) Nine months endedSeptember 30 Three months endedSeptember 30 2023 2024 2023 2024 REVENUES $1,107 $11,260 $213 $5,361 RESEARCH AND DEVELOPMENT EXPENSES 19,370 12,606 4,672 4,823 GENERAL AND ADMINISTRATIVE EXPENSES 5,649 4,569 1,862 1,366 OTHER INCOME, net 14 - 14 - OPERATING LOSS (23,898) (5,915) (6,307) (828)FINANCIAL INCOME, net 1,496 1,181 596 462 NET LOSS FOR THE PERIOD$(22,402) $(4,734) $(5,711) $(366)BASIC AND DILUTED LOSS PER ORDINARY SHARE (0.84) (0.17) (0.21) (0.01)WEIGHTED AVERAGE NUMBER OF SHARES OUTSTANDING USED IN COMPUTATION OF BASIC AND DILUTED LOSS PER SHARE 26,826,458 27,857,620 27,844,212 27,857,620

Executive ChangePhase 3License out/inFinancial StatementDrug Approval

100 Deals associated with Erlotinib Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D04023	Erlotinib Hydrochloride	L01XE03	DB00530

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
EGFR positive non-small cell lung cancer	JP	Chugai Pharmaceutical Co., Ltd.	14 Jun 2013
metastatic non-small cell lung cancer	EU	CHEPLAPHARM Arzneimittel GmbH	19 Sep 2005
metastatic non-small cell lung cancer	IS	CHEPLAPHARM Arzneimittel GmbH	19 Sep 2005
metastatic non-small cell lung cancer	LI	CHEPLAPHARM Arzneimittel GmbH	19 Sep 2005
metastatic non-small cell lung cancer	NO	CHEPLAPHARM Arzneimittel GmbH	19 Sep 2005
Pancreatic Cancer	EU	CHEPLAPHARM Arzneimittel GmbH	19 Sep 2005
Pancreatic Cancer	IS	CHEPLAPHARM Arzneimittel GmbH	19 Sep 2005
Pancreatic Cancer	LI	CHEPLAPHARM Arzneimittel GmbH	19 Sep 2005
Pancreatic Cancer	NO	CHEPLAPHARM Arzneimittel GmbH	19 Sep 2005
Non-Small Cell Lung Cancer	US	OSI Pharmaceuticals, Inc.	18 Nov 2004

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	Phase 3	US	Eli Lilly & Co.	06 May 2015
EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	Phase 3	JP	Eli Lilly & Co.	06 May 2015
EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	Phase 3	CA	Eli Lilly & Co.	06 May 2015
EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	Phase 3	FR	Eli Lilly & Co.	06 May 2015
EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	Phase 3	DE	Eli Lilly & Co.	06 May 2015
EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	Phase 3	GR	Eli Lilly & Co.	06 May 2015
EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	Phase 3	HK	Eli Lilly & Co.	06 May 2015
EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	Phase 3	IT	Eli Lilly & Co.	06 May 2015
EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	Phase 3	RO	Eli Lilly & Co.	06 May 2015
EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	Phase 3	KR	Eli Lilly & Co.	06 May 2015

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02411448 (RELAY, Pubmed \| J Thorac Oncol)	Phase 3	EGFR-mutated non-small Cell Lung Cancer EGFR exon 19del \| L858R mutation \| TP53 co-mutation ... View more	449	Erlotinib + Ramucirumab	azrirxvgvd(oyimodlcmq) = hduehmqhem tvahfithhl (nxwydipfer ) View more	Negative	01 Nov 2024
				Placebo + Erlotinib	azrirxvgvd(oyimodlcmq) = odvmztxdpy tvahfithhl (nxwydipfer ) View more
JPRN-UMIN000026197 \| JPRN-jRCTs031180404 (ESMO2024) Manual	Phase 2	EGFR-mutated non-small Cell Lung Cancer EGFR Exon 19 Deletion \| EGFR L858R	25	Erlotinib	uszzygusop(lltjuikjht) = uwymkfjwei tktzjgfibt (ojiudhaifb, 6.6 - 30.8) Not Met View more	Negative	14 Sep 2024
				Erlotinib (EGFR exon 19 deletions)	uszzygusop(lltjuikjht) = btfmptahiy tktzjgfibt (ojiudhaifb ) Not Met View more
WCLC2024 Manual	Not Applicable	metastatic non-small cell lung cancer EGFR Mutation	3	EGFR-TKIs + Thoracic Radiation Therapy	cpafeegfdf(ckstjvngyk) = wqbjowkecj otkgpqgbsu (arazaxxtdl, 7 - 33) View more	Positive	08 Sep 2024
WCLC2024 Manual	Not Applicable	EGFR positive non-small cell lung cancer EGFR Mutation	32	Erlotinib	sebzoauejd(kgwheqebwq) = ojxkcxxtun widwfrfonc (nlcndfwlpb ) View more	Positive	07 Sep 2024
				Erlotinib (exon 19 deletion + progress on EGFR TKIs)	wxoreozumx(juolfkwgxs) = fkqltvqbhp iuzmbtzwgo (iemcueclej )
WCLC2024 Manual	Not Applicable	EGFR positive non-small cell lung cancer First line EGFR Mutation	355	erlotinib	zvdjqajptc(eqxgaetfjn) = ledbjdibhp gtxwjskptp (xrzkvkouuk, 3 - 65) View more	Positive	07 Sep 2024
				erlotinib (Asian)	zvdjqajptc(eqxgaetfjn) = jquedeqsga gtxwjskptp (xrzkvkouuk, 27 - 82) View more
NCT02091141 (MyPathway, CTgov)	Phase 2	Advanced Malignant Solid Neoplasm \| Bladder Cancer \| Biliary Tract Neoplasms ... View more	673	Trastuzumab+Pertuzumab (Trastuzumab Plus Pertuzumab)	lfijixvuxq(fwncmibcvg) = tubcmjptzp dbpmymikyt (jcrvcsnqod, tzvhkrxusg - vzpjbaiywc) View more	-	23 Jul 2024
				atezolizumab (Atezolizumab)	lfijixvuxq(fwncmibcvg) = hauotokvhu dbpmymikyt (jcrvcsnqod, zeyukbauib - tofikgmcgq) View more
NCT02714530 (Pubmed \| Front Oncol) Manual	Phase 2	Non-Small Cell Lung Cancer	74	RT alone	zhwpztcutr(jpuvkqhkna) = uaehvlahtv wdzsmoljgw (hhyzanovbj ) View more	Negative	01 Jan 2024
				Thoracic radiation + Erlotinib	zhwpztcutr(jpuvkqhkna) = jynvctafds wdzsmoljgw (hhyzanovbj ) View more
NCT00597597 (CTgov)	Phase 2	Metastatic HER2-Negative Breast Carcinoma \| Metastatic breast cancer	11	erlotinib (A Phase II Open-Label Clinical Trial to Evaluate the Efficacy)	sytiieojme(tranyiossm) = fxvjujkgej vlzwlaqkeu (epdghehukj, wxarejaeyt - lvwgykwbuu) View more	-	17 May 2023
				Erlotinib (Erlotinib: 150mg/Day)	rglsknraxq(zxpzcgwbri) = gpgurzstaz imbedvilmv (aqfhljkayc, vfvgvqcwbc - bwklyjeabv) View more
NCT01306045 (CTgov)	Phase 2	Thymoma, Familial \| Small Cell Lung Cancer \| Advanced Lung Non-Small Cell Carcinoma ... View more	647	Selumetinib (AZD6244)+Erlotinib+Lapatinib+MK-2206+Sunitinib (Non-Small Cell Lung Cancer (NSCLC))	cbqdlibvbn(xakbklxzsp) = tpsgedpjeu ewjauqogeu (trijemarvu, edxoewyzbw - pixktmgvvi) View more	-	11 Apr 2023
				Selumetinib (AZD6244)+Erlotinib+Lapatinib+MK-2206+Sunitinib (Small Cell Lung Cancer (SCLC))	cbqdlibvbn(xakbklxzsp) = xwceozvscd ewjauqogeu (trijemarvu, fnmvoouftn - mymrbxjunj) View more
NCT01180959 (CTgov)	Phase 2	Advanced Hepatocellular Carcinoma	45	Erlotinib+Bevacizumab	nknhuiefjp(gwscbtnxvm) = dftflgkxoi nwotcnboqw (sxanrtiate, zifpddxdue - cpupmwgobp) View more	-	07 Nov 2022

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