On September 9, 2023 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a commercial stage research and development, biotechnology company, reported two-year follow-up data from a pooled analysis of the Phase 1/1b Cohort and Phase 2 Cohort A for the KRYSTAL-1 study evaluating adagrasib (KRAZATI) in patients with non-small cell lung cancer (NSCLC) harboring a KRASG12C mutation (Press release, Mirati, SEP 9, 2023, View Source [SID1234635043]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In the pooled analysis, adagrasib demonstrated durable efficacy with a median overall survival (OS) of 14.1 months and a 2-year OS rate of 31% in patients with previously treated KRASG12C-mutated NSCLC. Exploratory analyses suggested clinical benefit in patients with treated, stable central nervous system (CNS) metastases at baseline with clinical benefit noted across most baseline co-mutations.

In the study, adagrasib demonstrated a manageable long-term safety profile with low grade treatment-related adverse events (TRAEs). Hepatotoxicity was not observed in any patients who received adagrasib within 30 days of prior immunotherapy and, overall, there was a low rate of grade >3 hepatoxicity.

A confirmatory Phase 3 study, KRYSTAL-12, is ongoing, evaluating adagrasib vs. docetaxel in previously treated patients with KRASG12C-mutated NSCLC.

"This data reinforces the ability of adagrasib to positively impact patients as a potential best in class option," said Alan Sandler, M.D., chief medical officer, Mirati Therapeutics, Inc. "Adagrasib offers a differentiated option for KRASG12C-mutated NSCLC as evidenced by its clinical activity in the CNS and ability to sequence adagrasib immediately after prior immunotherapy. We look forward to continuing to advance adagrasib across lines of therapy in a range of tumor types for the benefit of patients living with KRASG12C-mutated cancer."

"These data continue to reinforce the benefit of adagrasib for patients living with KRASG12C-mutated NSCLC who are in need for better options than the historical standard of care chemotherapy," Shirish M. Gadgeel, MD, head, the Division of Hematology/Oncology, associate director, Patient Experience and Clinical Care, the Henry Ford Cancer Institute. "The long term overall survival for adagrasib is meaningful for patients."

In December of 2022, adagrasib was added to the National Comprehensive Center Network (NCCN) Guidelines for patients living with previously treated KRASG12C-mutant NSCLC. Following, adagrasib was added the NCCN guidelines for CNS Cancers for patients living with previously treated KRASG12C-mutant NSCLC and CNS metastases.

About KRAZATI (adagrasib)

In the U.S., KRAZATI was approved by the FDA for Accelerated Approval (Subpart H), which allows for the approval of drugs that treat serious conditions, and that fill an unmet medical need based on surrogate endpoints. KRAZATI was reviewed under the FDA Real-Time Oncology Review (RTOR) pilot program, which aims to explore a more efficient review process that ensures safe and effective treatments are made available to patients as early as possible. Mirati submitted a Marketing Authorization Application (MAA) in the EU in May 2022. In 2021, adagrasib achieved Breakthrough Therapy Designation in the U.S. as a potential treatment for patients with NSCLC harboring the KRASG12C mutation who have received at least one prior systemic therapy. For Prescribing Information, visit Mirati.com/KRAZATI_USPI.

Adagrasib continues to be evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including NSCLC, colorectal cancer, and pancreatic cancer. For more information, visit Mirati.com/science.

KRAZATI (adagrasib) U.S. Indication

KRAZATI is indicated for the treatment of adult patients with KRASG12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s).

KRAZATI (adagrasib) Important Safety Information

WARNINGS AND PRECAUTIONS

Gastrointestinal Adverse Reactions

In the pooled safety population, serious gastrointestinal adverse reactions observed were gastrointestinal obstruction in 1.6%, including 1.4% grade 3 or 4, gastrointestinal bleeding in 0.5% of patients, including 0.5% grade 3, and colitis in 0.3%, including 0.3% grade 3. In addition, nausea, diarrhea, or vomiting occurred in 89% of 366 patients, including 9% grade 3. Nausea, diarrhea, or vomiting led to dosage interruption or dose reduction in 29% of patients and permanent discontinuation of KRAZATI in 0.3%
Monitor and manage patients using supportive care, including antidiarrheals, antiemetics, or fluid replacement, as indicated. Withhold, reduce the dose, or permanently discontinue KRAZATI based on severity
QTc Interval Prolongation

KRAZATI can cause QTc interval prolongation, which can increase the risk for ventricular tachyarrhythmias (eg, torsades de pointes) or sudden death
In the pooled safety population, 6% of 366 patients with at least one post-baseline electrocardiogram (ECG) assessment had an average QTc ≥501 ms, and 11% of patients had an increase from baseline of QTc >60 msec. KRAZATI causes concentration-dependent increases in the QTc interval
Avoid concomitant use of KRAZATI with other products with a known potential to prolong the QTc interval. Avoid use of KRAZATI in patients with congenital long QT syndrome and in patients with concurrent QTc prolongation
Monitor ECGs and electrolytes prior to starting KRAZATI, during concomitant use, and as clinically indicated in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, and in patients who are taking medications that are known to prolong the QT interval. Withhold, reduce the dose, or permanently discontinue KRAZATI, depending on severity
Hepatotoxicity

KRAZATI can cause hepatotoxicity
In the pooled safety population, hepatotoxicity occurred in 37%, and 7% were grade 3 or 4. A total of 32% of patients who received KRAZATI had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 5% were grade 3 and 0.5% were grade 4. Increased ALT/AST leading to dose interruption or reduction occurred in 11% of patients. KRAZATI was discontinued due to increased ALT/AST in 0.5% of patients
Monitor liver laboratory tests (AST, ALT, alkaline phosphatase, and total bilirubin) prior to the start of KRAZATI, and monthly for 3 months or as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Reduce the dose, withhold, or permanently discontinue KRAZATI based on severity
Interstitial Lung Disease /Pneumonitis

KRAZATI can cause interstitial lung disease (ILD)/pneumonitis, which can be fatal. In the pooled safety population, ILD/pneumonitis occurred in 4.1% of patients, 1.4% were grade 3 or 4, and 1 case was fatal. The median time to first onset for ILD/pneumonitis was 12 weeks (range: 5 to 31 weeks). KRAZATI was discontinued due to ILD/pneumonitis in 0.8% of patients
Monitor patients for new or worsening respiratory symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Withhold KRAZATI in patients with suspected ILD/pneumonitis and permanently discontinue KRAZATI if no other potential causes of ILD/pneumonitis are identified
Adverse Reactions

The most common adverse reactions (≥25%) are nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, renal impairment, edema, dyspnea, decreased appetite
Females and Males of Reproductive Potential

Infertility: Based on findings from animal studies, KRAZATI may impair fertility in females and males of reproductive potential
Please see Full Prescribing Information.

On September 8, 2023 Haihe Biopharma K. K. (referred as "Company"), fully owned affiliate of Shanghai Haihe Biopharma Co., Ltd (China) reported that the New Drug Application ("NDA") of Gumarontinib (SCC244) for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with MET exon 14 (METex14) skipping mutation, has been filed to Ministry of Health, Labour and Welfare(厚生労働省) (Press release, Shanghai HaiHe Pharmaceutical, SEP 8, 2023, View Source [SID1234646872]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The indication application is based on the data from the SCC244-108 a pivotal Phase II study (GLORY study), a global multi-center, open-label, single-arm clinical trial to evaluate the efficacy and safety of Gumarontinib in locally advanced or metastatic NSCLC patients with METex14 skipping mutations. This indication has been approved by NMPA in China on March 7, 2023. The global leading principal investigator is Prof. Shun Lu at Shanghai Chest Hospital，China.

Dr. Ruiping Dong, Chief Executive Officer of Haihe Biopharma, stated,
"The file in Japan for Gumarontinib, demonstrates Haihe’s mission for the global development of the innovative drugs to bring more effective and much safer treatment options for cancer patients around the world, and marks a historic step of Haihe Biopharma’s innovative drug into the global market. We deeply appreciated the contribution from the patients and the efforts from the investigators, and the recognition of Gumarontinib. Haihe Biopharma will continue to file more global New Drug Applications to benefit cancer patients in the world."
Prof. Shun Lu, the global leading principal investigator of the GLORY study, from the Oncology Department of Shanghai Chest Hospital, commented,
"Gumarontinib is an oral, potent and highly selective MET inhibitor. The GLORY study data demonstrated that Gumarontinib has solid efficacy and good safetyin the treatment naive or previously treated NSCLC patients harboring METex14 skipping mutations, even those with brain metastases. We expect Gumarontinib with better efficacy and acceptable safety could address the unmet needs of patients in China and globally."
About NSCLC and METex14 Skipping Mutations
Primary lung cancer is the malignant tumor with the highest morbidity and mortality in China. NSCLC accounts for approximately 85% of all lung cancers1. The total incidence of METex14 skipping mutations in NSCLC is about 3%2, and the incidence in Chinese NSCLC population is about 1.3%3.
METex14 skipping mutations is a primary oncogenic driver gene, which usually does not coexist with other lung cancer mutations such as EGFR, KRAS and ALK4. Most patients were elderly, with a median age of 72.5 years5. METex14 skipping mutations predicted poor prognosis, with progression-free survival (PFS) of only 2.9 months, overall survival (OS) of 7.9 – 8.3 months, and objective response rate (ORR) of 8.8% — 9.1%6 in second-line chemotherapy. NSCLC patients with METex14 skipping mutations were insensitive to PD-1 therapy with ORR ranged from 16 to 17%, median PFS ranged from 1.9 to 3.4 months, and there was no increase in response rate among tumor patients with high PD-L1 expression7,8 In Japan, the number of new lung cancer patients is 120,000/year (2020) and the number of deaths is 70,000 /year 1. The proportion of non-small cell lung cancer among lung cancer patients in Japan is 88%, and the frequency of METex14 skipping mutation-positive expression is about 3%3. Thus, in Japan, the number of patients that may be eligible for treatment with this drug is estimated to be around 3,000/year.

About Gumarontinib (SCC244)
Gumarontinib (code: SCC244) is an oral, potent and highly selective small molecule MET inhibitor. Gumarontinib has shown excellent pharmacokinetic characteristics, highly effective and durable efficacy and favorable safety profile in NSCLC patients with MET alterations. As of today, compared with its competitors, Gumarontinib has long half-life to achieve sustained target inhibition, low DDI potential withless co-medication restrictions, convenient QD regimen. Gumarontinib has been approved by the NMPA in China with breakthrough designation for the treatment of non-small cell lung cancer (NSCLC) with MET genomic aberration.

On September 8, 2023 Biocept, Inc. (Nasdaq: BIOC), a leading provider of molecular diagnostic assays, products, and services, reported the signing of a non-exclusive licensing agreement for CNSide with Plus Therapeutics, Inc. (Nasdaq: PSTV) (Plus), which expands the comprehensive laboratory services agreement between the two companies that was announced in June 2022 (Press release, Biocept, SEP 8, 2023, View Source [SID1234635038]). Plus is using CNSide in a clinical trial with their targeted radiotherapeutic to treat patients with carcinomas and/or melanomas with suspected leptomeningeal metastases (LM), which is cancer in the membranes that surround the brain and spinal cord. CNSide is Biocept’s proprietary cerebrospinal fluid (CSF)-based tumor cell capture and enumeration platform used in detecting, quantifying, and monitoring tumor status in LM.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This new agreement allows for Plus to perform CNSide testing during its clinical trials and commercially, subject to regulatory approval. Biocept will provide expertise, including consulting on equipment and materials sourcing, as well as providing the necessary technology and training to perform CNSide. Plus will pay Biocept an upfront fee of $150,000 in stock, plus $6,000 per CSF tumor cell enumeration analysis performed in Biocept’s CLIA-certified and CAP-accredited laboratory prior to the completion of the technology transfer. Once the technology transfer is complete, Plus will pay Biocept $300,000 plus fees on a sliding scale starting at $2,800 for each CNSide test they perform. The license agreement also gives Plus the option to negotiate for third-party exclusivity with a $1,000,000 payment to Biocept.

"We are gratified that Plus continues to recognize the value of CNSide in leptomeningeal metastases disease management. We share their commitment to improving the lives of patients suffering from cancer of the central nervous system (CNS)," said Antonino Morales, Biocept President and CEO. "We view this agreement as further validation of the clinical utility of CNSide and the important role it plays in diagnosing and monitoring patients with LM. It also sets the stage for future agreements with other companies developing treatments for cancer of the CNS and provides Biocept with non-dilutive funding to support our goal of establishing CNSide as standard of care under the National Comprehensive Cancer Network (NCCN) guidelines.

"Importantly, Plus will reimburse Biocept for CNSide testing performed prior to completion of the technology transfer at $6,000 per enumeration," he added. "This amount more than covers our costs and potentially sets the stage for reimbursement at a similar level in future arrangements."

Plus is using CNSide in its ReSPECT-LM Phase 1/2a dose-escalation clinical trial of Rhenium 186 Obisbemeda for the treatment of patients with LM. Plus recently announced completion of Phase 1/Part A of the trial and presented favorable preliminary safety and efficacy results. Plus has received U.S. Food and Drug Administration (FDA) approval to move to Phase 1/Part B of the ReSPECT-LM clinical trial. For more information on Plus, please visit www.plustherapeutics.com.

"The CNSide test is the emerging gold standard for the definitive diagnosis and follow up of patients with LM," said Marc H. Hedrick, M.D., President and CEO of Plus Therapeutics. "The CNSide technology may, in the near future, supplement or replace existing diagnostic technology for cerebrospinal fluid malignancies. We view CNSide as an important complement to our novel radiotherapeutic technology, Rhenium 186 Obisbemeda, now in clinical development for leptomeningeal metastases in our actively enrolling ReSPECT-LM trial."

About CNSide

CNSide is a laboratory developed test (LDT) based on Biocept’s proprietary quantitative tumor cell capture and detection method, paired with assays to identify actionable molecular treatment targets. Given the genetic changes that can occur as metastatic cancer spreads to the CNS, the evaluation of cerebrospinal fluid with CNSide provides a unique opportunity to identify biomarkers in patients with metastatic carcinoma or melanoma to help guide physicians in therapy selection. In addition, the quantitative tumor cell count assay can be used in a serial fashion to monitor the response to therapy more effectively than other current methods.

On September 8, 2023 Novocure (NASDAQ: NVCR) reported its participation in the upcoming International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer (WCLC) from September 9 – 13, 2023 in Singapore (Press release, NovoCure, SEP 8, 2023, View Source [SID1234635037]). Novocure will take part in presentations and symposia throughout the event and will exhibit several posters exploring the use of Tumor Treating Fields (TTFields) therapy in the treatment of lung cancer, including a new post-hoc analysis of data from its LUNAR trial in metastatic non-small cell lung cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The LUNAR trial was designed to evaluate the use of TTFields therapy together with standard systemic therapies for the treatment of metastatic non-small cell lung cancer, following progression on or after platinum-based therapy. The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful extension in overall survival (OS) for patients treated with TTFields and standard systemic therapies, as well as a pronounced extension in OS for patients randomized to receive physician’s choice immune checkpoint inhibitor (ICI) together with TTFields.

In a new post-hoc analysis of data from the LUNAR trial, researchers reviewed survival patterns of patients with known Tumor Proportion Scores (TPS) randomized to receive ICI together with or without TTFields. Among patients with TPS >1%, median OS for patients treated with TTFields therapy and ICI (n=22) was 23.6 months compared to 10.5 months for patients treated with ICI alone (n=26; HR: 0.49, P=0.045).

Further analysis shows evidence of a relationship between increasing PD-L1 expression and improved survival outcomes. In patients with TPS 1–49%, median OS was 19.0 months for patients treated with TTFields therapy and ICI (n=17), compared to 9.7 months for patients treated with ICI alone (n=18; HR: 0.55, P=0.14). In patients with TPS >50%, median OS was not reached for patients treated with TTFields therapy and ICI (n=5) compared to 30.0 months for patients treated with ICI alone (n=8; HR: 0.17, P=0.07).

These data will be presented on September 12, 2023 at 2:30 p.m. UTC+8 by primary investigator Ticiana Leal, M.D., a researcher and medical oncologist at Winship Cancer Institute of Emory University and associate professor and director of the Thoracic Medical Oncology Program in the Department of Hematology and Medical Oncology at Emory University School of Medicine in Atlanta.

"This analysis further elucidates the promising results from the LUNAR trial and the potential benefit of utilizing TTFields therapy for the treatment of metastatic non-small cell lung cancer," Dr. Leal said. "I look forward to sharing these data with the global thoracic oncology community and continuing to analyze the data from this impactful study."

Novocure’s presence at the 2023 WCLC will also include:

An Industry Sponsored Symposium: A Spotlight on Tumor Treating Fields in Thoracic Oncology, on September 10 at 6:30 p.m. UTC+8
A poster displayed in the Exhibit Hall on September 10 from 5:30-7:30 p.m. UTC+8: P1.12-10 – Sensitization of Cancer Cells to Tumor Treating Fields (TTFields) via Inhibition of the PI3K/AKT Signaling Pathway
Three ePosters on demand:
EP02.02-02 – Transcriptomic Response to Tumor Treating Fields (TTFields) Across Tumor Types
EP09.02-06 – Long-term Efficacy of Tumor Treating Fields (TTFields 150 kHz) in metastatic NSCLC: A Case Report
EP17.03-02 – Utilities Used in HTAs in mNSCLC Following Progression on or After Platinum-Based Chemotherapy
In addition, Novocure is partnering with the IASLC, host of the WCLC, to provide research opportunities to investigators worldwide who are conducting innovative research on TTFields in the treatment of non-small cell lung cancer and other thoracic malignancies. These grants offer $100,000 to fund projects to be completed in a two-year timeframe.

"We are honored to partner with the IASLC in their mission to study and eradicate lung cancer and other thoracic malignancies," said Moshe Giladi, Ph.D., Novocure’s Chief Science Officer. "We look forward to supporting researchers and together expanding understanding of how TTFields therapy can be beneficial in the treatment of these diseases."

To learn more about these grants, please visit View Source application deadline is noon MDT on October 9, 2023.

About LUNAR

LUNAR was a phase 3 trial testing the safety and effectiveness of TTFields therapy when used together with ICI or docetaxel versus ICI or docetaxel alone for patients with metastatic NSCLC who progressed during or after platinum-based therapy. The trial met its primary endpoint, exhibiting a statistically significant and clinically meaningful improvement in median OS when TTFields therapy was added to standard therapies. Patients randomized to receive TTFields therapy together with standard therapies (n=137) demonstrated median OS of 13.2 months compared to 9.9 months in patients treated with standard therapies alone (n=139; HR: 0.74, P=0.035).

The trial also demonstrated a statistically significant and clinically meaningful improvement in median OS when TTFields therapy was added to ICI. Patients randomized to receive TTFields therapy and physician’s choice ICI (n=66) demonstrated a median OS of 18.5 months versus a median OS of 10.8 months in patients treated with ICIs alone (n=68; HR=0.63; P=0.03). Patients randomized to receive TTFields therapy and docetaxel (n=71) had a positive survival trend with a median OS of 11.1 months vs 8.7 months in patients treated with docetaxel alone (n=71). TTFields therapy was well-tolerated with no added systemic toxicities and few grade 3 (no grade 4 or 5) device-related adverse events.

TTFields therapy is intended principally for use with other concomitant standard therapies, and LUNAR was designed to generate data that contemplates multiple outcomes, all of which Novocure believes will be clinically meaningful.

About NSCLC

Lung cancer is the most common cause of cancer-related death worldwide, and NSCLC accounts for approximately 85% of all lung cancers. It is estimated that approximately 193,000 patients are diagnosed with NSCLC each year in the U.S. Physicians use different combinations of surgery, radiation and pharmacological therapies to treat NSCLC, depending on the stage of the disease. Surgery, which may be curative in a subset of patients, is usually used in early stages of the disease. Since 1991, radiation with a combination of platinum-based chemotherapy drugs has been the first-line standard of care for locally advanced or metastatic NSCLC. Certain immune checkpoint inhibitors have been approved for the first-line treatment of NSCLC and the standard of care in this setting appears to be evolving rapidly. The standard of care for second-line treatment is also evolving and may include platinum-based chemotherapy for patients who received immune checkpoint inhibitors as their first-line regimen, docetaxel, immune checkpoint inhibitors or pemetrexed. It is estimated that approximately 46,000 patients receive second-line treatment for metastatic NSCLC each year in the U.S.

On September 8, 2023 Citius Pharmaceuticals, Inc. ("Citius" or the "Company") (Nasdaq: CTXR) reported that the Company has received additional guidance from the U.S. Food and Drug Administration (FDA) regarding the planned resubmission of the Company’s Biologics License Application (BLA) for LYMPHIR (denileukin diftitox), an engineered IL-2-diphtheria toxin fusion protein for the treatment of patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy (Press release, Citius Pharmaceuticals, SEP 8, 2023, View Source [SID1234635036]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The FDA has agreed with the Company’s plans to address the requirements outlined in the complete response letter (CRL) received July 28, 2023. The guidance from the FDA provides Citius with a path for completing the necessary activities to support the resubmission of the Company’s Biologics License Application (BLA) for denileukin diftitox. No additional clinical efficacy or safety trials have been requested by FDA for the resubmission.

"We are encouraged by the constructive engagement with the FDA," stated Leonard Mazur, Chairman and CEO of Citius. "Based on the clear feedback from the FDA, Citius plans to complete the CRL remediation activities by the end of the year and file the resubmission in early 2024. We do not expect these efforts will impact our cash runway."

About LYMPHIR (denileukin diftitox-cxdl)

LYMPHIR is a recombinant fusion protein that combines the interleukin-2 (IL-2) receptor binding domain with diphtheria toxin fragments. The agent specifically binds to IL-2 receptors on the cell surface, causing diphtheria toxin fragments that have entered cells to inhibit protein synthesis. In 2011 and 2013, the FDA granted orphan drug designation to LYMPHIR for the treatment of PTCL and CTCL, respectively. In 2021, denileukin diftitox received regulatory approval in Japan for the treatment of CTCL and peripheral T-cell lymphoma (PTCL). Subsequently in 2021, Citius acquired an exclusive license with rights to develop and commercialize LYMPHIR in all markets except for Japan and certain parts of Asia.

About Cutaneous T-cell Lymphoma

Cutaneous T-cell lymphoma is a type of cutaneous non-Hodgkin lymphoma (NHL) that comes in a variety of forms and is the most common type of cutaneous lymphoma. In CTCL, T-cells, a type of lymphocyte that plays a role in the immune system, become cancerous and develop into skin lesions, leading to a decrease in the quality of life of patients with this disease due to severe pain and pruritus. Mycosis Fungoides (MF) and Sézary Syndrome (SS) comprise the majority of CTCL cases. Depending on the type of CTCL, the disease may progress slowly and can take anywhere from several years to upwards of ten to potentially reach tumor stage. However, once the disease reaches this stage, the cancer is highly malignant and can spread to the lymph nodes and internal organs, resulting in a poor prognosis. Given the duration of the disease, patients typically cycle through multiple agents to control disease progression. CTCL affects men twice as often as women and is typically first diagnosed in patients between the ages of 50 and 60 years of age. Other than allogeneic stem cell transplantation, for which only a small fraction of patients qualify, there is currently no curative therapy for advanced CTCL.