On December 13, 2022 Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical biotechnology company with a robust pipeline of investigational therapeutics built on protein dysregulation expertise, reported that it has commenced an underwritten public offering of 3,000,000 of its ordinary shares (Press release, Prothena, DEC 13, 2022, View Source [SID1234625237]). All of the ordinary shares in the offering will be sold by Prothena. In addition, Prothena expects to grant the underwriters a 30-day option to purchase up to an additional 15% of the number of ordinary shares sold.

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!

Jefferies, Evercore ISI and Cantor are acting as joint book-running managers for the offering. The offering is subject to market conditions, and there can be no assurance as to whether or when the offering will be completed, or as to the actual size or terms of the offering.

The proposed public offering will be made pursuant to an automatic shelf registration statement on Form S-3 that was filed with the Securities and Exchange Commission (the "SEC") on March 23, 2021 and automatically became effective upon filing. A preliminary prospectus supplement and accompanying prospectus relating to and describing the terms of the offering will be filed with the SEC and available on the SEC’s website located at View Source or may be obtained by contacting Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, NY 10022, or by telephone at (877) 821-7388, or by e-mail at [email protected]; Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 35th Floor, New York, NY 10055, or by telephone at (888) 474-0200, or by email at [email protected]; or Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Avenue, 4th Floor, New York, NY 10022, or by e-mail at [email protected].

On December 13, 2022 Optime Care, a member of the AscellaHealth Family of Companies, reported a contractual partnership with Rigel Pharmaceuticals, Inc., bringing its full suite patient support/HUB service capabilities to support Rezlidhia(olutasidenib), a recent FDA-approved treatment for adult patients with relapse or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test (Press release, Rigel, DEC 13, 2022, View Source [SID1234625235]). Optime Care’s services for life sciences manufacturers include pre-commercialization and market access expertise, exclusive distribution partnerships, national medication fulfillment and high-touch patient support and HUB services for enhanced patient outcomes.

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!

"Our dedicated team of highly experienced nurse navigators and case managers looks forward to implementing a custom, branded program for Rigel Pharmaceuticals, enabling Rezlidhia patients to experience optimal therapeutic outcomes and the best possible treatment journey."

Tweet this
Brandon Salke, general manager and pharmacist-in-charge, says, "Our dedicated team of highly experienced nurse navigators and case managers looks forward to implementing a custom, branded program for Rigel Pharmaceuticals, enabling Rezlidhia patients to experience optimal therapeutic outcomes and the best possible treatment journey."

Rigel Pharmaceuticals, Inc. has a long-standing relationship with Optime Care and has selected them for the management of Rezlidhia patients based upon its rare disease expertise and comprehensive suite of integrated patient management and HUB services including distribution, patient intake, prescription fulfillment, prior authorization support, custom clinical programs, reimbursement services and financial assistance.

Scott Yohe, Vice President Market Access at Rigel Pharmaceuticals, says, "We are excited to work with Optime Care in the complete management of our Rezlidhia patients. Optime Care’s patient-first and collaborative approach to patient management of rare disease patients enables us to take advantage of their comprehensive expertise and knowledge which are critical to ensuring that Rezlidhia patients receive the best care possible for an optimal treatment journey and enhanced clinical outcomes."

About REZLIDHIA

INDICATION

REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Differentiation syndrome, which can be fatal, can occur with REZLIDHIA treatment. Symptoms may include dyspnea, pulmonary infiltrates/pleuropericardial effusion, Kidney injury, hypotension, fever, and weight gain. If differentiation syndrome is suspected, withhold REZLIDHIA and initiate treatment with corticosteroids and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome

REZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis.

If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms. Differentiation syndrome may recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction based on recurrence.

Hepatotoxicity

REZLIDHIA can cause hepatotoxicity, presenting as increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood alkaline phosphatase, and/or elevated bilirubin. Of 153 patients with relapsed or refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients; 13% experienced grade 3 or 4 hepatotoxicity. One patient treated with REZLIDHIA in combination with azacitidine in the clinical trial, a combination for which REZLIDHIA is not indicated, died from complications of drug-induced liver injury. The median time to onset of hepatotoxicity in patients with relapsed or refractory AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to 17 months). The most common hepatotoxicities were elevations of ALT, AST, blood alkaline phosphatase, and blood bilirubin.

Monitor patients frequently for clinical symptoms of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Obtain baseline liver function tests prior to initiation of REZLIDHIA, at least once weekly for the first two months, once every other week for the third month, once in the fourth month, and once every other month for the duration of therapy. If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue REZLIDHIA based on recurrence/severity.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis.

DRUG INTERACTIONS

Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers.

Avoid concomitant use of REZLIDHIA with sensitive CYP3A substrates unless otherwise instructed in the substrates prescribing information. If concomitant use is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

LACTATION

Advise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose.

GERIATRIC USE

No overall differences in effectiveness were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase inincidence of hepatotoxicity and hypertension was observed in patients ≥65 years of age.

HEPATIC IMPAIRMENT

In patients with mild or moderate hepatic impairment, closely monitor for increased probability of differentiation syndrome.

Click here for Full Prescribing Information, including Boxed WARNING.

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).

REZLIDHIA is a trademark of Rigel Pharmaceuticals, Inc.

On December 13, 2022 ESSA Pharma Inc. ("ESSA", or the "Company") (NASDAQ: EPIX), a clinical-stage pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, reported a corporate update and reported financial results for the fiscal year ended September 30, 2022 (Press release, ESSA, DEC 13, 2022, View Source [SID1234625234]). All references to "$" in this release refer to United States dollars, unless otherwise indicated.

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!

"ESSA achieved major milestones in 2022 with the release of Phase 1 monotherapy and combination data for our lead candidate EPI-7386 from three clinical trials in patients with metastatic castration-resistant prostate cancer ("mCRPC"), which demonstrated initial anti-tumor activity in certain patients, and EPI-7386’s favorable safety profile as a single agent and in combination with second-generation antiandrogens," stated David Parkinson, MD, President and CEO of ESSA. "Early data from these clinical studies demonstrated notable PSA reductions in the Phase 1 study of EPI-7386 and Astellas’ Xtandi (enzalutamide) and in the Phase 1 study of EPI-7386 and Janssen’s antiandrogens Erleada (apalutamide) and Zytiga (abiraterone acetate). In addition, the Phase 1a dose escalation monotherapy results showed tumor volume decreases and PSA declines in a subset of heavily pretreated mCRPC patients who had progressed on standard-of-care therapies."

Dr. Parkinson continued: "Looking ahead to 2023, we expect a busy year as we advance clinical studies of EPI-7386 as a monotherapy and in combination with approved antiandrogens in a number of prostate cancer patient populations. Our cash runway is strong and expected to fund our operations and clinical programs through 2025, including the Phase 1b monotherapy expansion and Window of Opportunity studies, a Phase 2 combination study with enzalutamide, additional cohorts in a Phase 1 study evaluating EPI-7386 with Janssen’s antiandrogens, and an investigator-sponsored study of EPI-7386 and darolutamide."

Clinical and Corporate Highlights for 2022 Fiscal Year

EPI-7386 Combination Studies

Updated clinical data from the first two cohorts of the Phase 1/2 study of EPI-7386 in combination with enzalutamide were presented at the 2022 Prostate Cancer Foundation ("PCF") Scientific Retreat. The data showed preliminary evidence of anti-tumor activity, with five of six patients achieving PSA90 and four of six patients achieving PSA90 within 90 days.
In October 2022, the Company announced that Janssen Research and Development is suspending enrollment into the Phase 1 clinical study of EPI-7386 with apalutamide or EPI-7386 with abiraterone acetate plus prednisone in mCRPC patients as a result of operational recruitment challenges. Before suspending enrollment, Janssen treated three mCRPC patients (chemotherapy naive) for up to four months of therapy, with two of the three patients achieving PSA90 within 90 days. ESSA anticipates enrolling additional cohorts in the Phase 1 study in 2023 to further assess the safety and tolerability of abiraterone acetate plus prednisone or apalutamide (administered at the dose recommended in their prescribing information) when administered in combination with EPI-7386 and to establish recommended Phase 2 dosing for these combinations.
Preclinical data for the Company’s lead first generation androgen receptor ANITen bAsed Chimera ("ANITAC") N-terminal domain degrader were presented in a poster session at the 34th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Annual Symposium on Molecular Targets and Cancer Therapeutics.
EPI-7386 Monotherapy

In June 2022, the Company presented a clinical update on EPI-7386 monotherapy and combination therapy clinical development. Initial data from 33 heavily pretreated mCRPC patients enrolled in the Phase 1a dose escalation monotherapy study demonstrated that EPI-7386 was well-tolerated and reached clinically relevant exposures at all dose levels tested. Clinically important signals of anti-tumor activity were observed in a subset of these patients (less than 3 lines of treatment for mCRPC, lack of visceral disease, no prior chemotherapy and lack or few non-AR mutations).
Corporate Updates

In September 2022, the Company announced the appointment of Philip Kantoff, M.D., to its Board of Directors. Dr. Kantoff is a renowned medical oncologist and leader in the clinical development of new prostate cancer treatments.
Summary Financial Results

Net Loss. ESSA recorded a net loss of $35.1 million for the year ended September 30, 2022, compared to a net loss of $36.8 million for the year ended September 30, 2021. For the year ended September 30, 2022, this included non-cash share-based payments of $7.9 million compared to $9.5 million for the prior year, recognized for stock options granted and vesting. The net loss for the fourth quarter ended September 30, 2022 was $6.3 million compared to a net loss of $8.5 million for the fourth quarter ended September 30, 2021. The decrease in the fourth quarter was primarily attributed to a decrease in research and development expenditures.
Research and Development ("R&D") expenditures. R&D expenditures for the year ended September 30, 2022 were $24.4 million compared to $24.3 million for the year ended September 30, 2021 and include non-cash costs related to share-based payments ($4.3 million for the year ended 2022 compared to $3.6 million for the year ended 2021). The R&D expenditures for the year ended September 30, 2022 largely remained consistent when compared to the year ended September 30, 2021, as the increased expense in preclinical and data analysis was offset by the decreased expense in manufacturing costs related to the Phase 1 clinical trial of EPI-7386. For the fourth quarter ended September 30, 2022, R&D expenditures were $4.4 million (net and gross), compared to $6.3 million (net and gross) for the fourth quarter ended September 30, 2021. The decrease in the fourth quarter was primarily attributed to a decrease in non-cash share-based payments, manufacturing costs and travel costs.
General and administration ("G&A") expenditures. G&A expenditures for the year ended September 30, 2022 were $12.5 million compared to $12.9 million for the year ended September 30, 2021 and include non-cash costs related to share-based payments of $3.6 million for the year ended 2022 compared to $5.8 million for the year ended 2021. For the fourth quarter ended September 30, 2022, G&A expenditures were $2.8 million, compared to $2.9 million for the fourth quarter ended September 30, 2021. The decrease in the full year and fourth quarter is the result of decreased professional fees as well as the decrease in non-cash share-based payments.
Liquidity and Outstanding Share Capital

At September 30, 2022, the Company had available cash reserves and short-term investments of $167.2 million reflecting the gross proceeds of the February 2021 financing of approximately $150.0 million and July 2020 financing of $48.9 million, less operating expenses in the intervening period. The Company’s cash position is expected to be sufficient to fund current and planned operations through 2025.

As of September 30, 2022, the Company had 44,073,076 common shares issued and outstanding.

In addition, as of September 30, 2022 there were 3,234,750 common shares issuable upon the exercise of warrants and broker warrants. This includes 2,920,000 prefunded warrants at an exercise price of $0.0001, and 314,750 warrants at a weighted average exercise price of $49.69. There were 7,902,061 common shares issuable upon the exercise of outstanding stock options at a weighted-average exercise price of $5.13 per common share.

About EPI-7386
EPI-7386 is an investigational, highly-selective, oral, small molecule inhibitor of the N-terminal domain of the androgen receptor. EPI-7386 is currently being studied in a Phase 1 clinical trial (NCT04421222) in men with castration-resistant prostate cancer ("CRPC") whose tumors have progressed on standard-of-care therapies and a Window of Opportunity study in patients with non-metastatic CRPC. The U.S. FDA has granted Fast Track designation to EPI-7386 for the treatment of adult male patients with mCRPC resistant to standard-of-care treatment. ESSA is also conducting a Phase 1/2 clinical trial (NCT05075577) of EPI-7386 in combination with enzalutamide in metastatic CRPC patients who have not yet been treated with second-generation antiandrogen therapies. ESSA retains all rights to EPI-7386 worldwide.

On December 13, 2022 Treadwell Therapeutics, a clinical-stage biotechnology company developing novel, small molecule therapeutics for highly aggressive cancers, reported a presentation for the Company’s CFI-400945 program, a first in class inhibitor of Polo-like Kinase 4 (PLK4) a critical regulator of centriole duplication, at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held from December 10-13, 2022 (Press release, Treadwell Therapeutics, DEC 13, 2022, View Source [SID1234625233]). The poster presentation described the preliminary results from the monotherapy dose optimization portion of the TWT-202 in advanced leukemias.

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!

"CFI-400945 had previously shown single agent complete remissions in refractory high risk AML. As we optimize dose for the agent in unselected leukemia patients in study TWT-202, we are encouraged by the continued signs of safety and tolerability with this oral dosing regimen," said Principal Investigator, Dr. Gautam Borthukar, MD, Professor, Department of Leukemia, Division of Cancer Medicine, MD Anderson Cancer Center.

"We look forward to dose selection for CFI-400945, and expansion into populations of interest, including patients with TP53 mutations, where there is substantial unmet need," said Dr. Michael Tusche, Co-CEO at Treadwell Therapeutics.

2022 ASH (Free ASH Whitepaper) Poster Presentations and Details:

Preliminary Results from a Phase 2 Open-Label, Multicenter, Dose Optimization Clinical Study of the Safety, Tolerability, and Pharmacokinetic (PK) and Pharmacodynamic (PD) Profiles of CFI-400945 As a Single Agent or in Combination with Azacitidine or Decitabine in Patients with Acute Myeloid Leukemia, Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia (TWT-202)

Publication Number: 4087
Session: 616; Poster III
Date and Time: December 12th, 2022, 6:00 PM-8:00 PM

Data presented on CFI-400945, an oral, first-in-class PLK4 inhbitor, showed a tolerable safety profile at the 32, 48 and 64 mg cohorts (N=12), with exposures being approximately dose linear. No dose limiting toxicities have been observed to date, suggesting further dose optimization is required. Five cases of stable disease have been observed – 3 per ELN with 1 at 48 mg, and 2 at 64 mg, as well as 2 at 48 mg per IWG. Adverse events (AEs) for CFI-400945 in this study were in line with those observed in previous studies in similar patient populations. Main AEs (any grade) were hematologic, gastrointestinal and metabolism/nutritional disorders. Most predominant severe AE was febrile neutropenia. No treatment emergent adverse events led to study drug discontinuation.

On December 13, 2022 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported the publication of a manuscript in Cancer Discovery, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), which describes the design and characterization of NVL-520 and details Nuvalent’s approach to rationally targeting ROS1 (Press release, Nuvalent, DEC 13, 2022, View Source [SID1234625232]). NVL-520 is currently being studied in the ongoing ARROS-1 Phase 1/2 clinical trial for patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) and other solid tumors.

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 paper, entitled "NVL-520 is a selective, TRK-sparing, and brain-penetrant inhibitor of ROS1 fusions and secondary resistance mutations," is published online and can be accessed here: View Source

"The ROS1 kinase is a clinically validated target for the treatment of NSCLC, and ROS1 tyrosine kinase inhibitors (TKIs) are established as an important treatment option for ROS1-driven lung cancers. However, limitations do exist with available ROS1 TKIs, including treatment-emergent drug resistance, off-target neurological adverse events, and inadequate control or prevention of brain metastases," said senior author Jessica J. Lin, M.D., Thoracic Oncologist at Mass General Cancer Center, Assistant Professor of Medicine at Harvard Medical School, and investigator in the ARROS-1 trial. "As described in this paper and earlier this year at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium, preclinical characterization and preliminary clinical data support the opportunity for NVL-520 to overcome these limitations as a potential best-in-class ROS1 kinase inhibitor and provide compelling rationale for its ongoing evaluation in patients with TKI-experienced ROS1 fusion-positive cancers and planned evaluation in treatment-naïve patients."

The paper details the design principles underlying the activity of NVL-520 against ROS1 and its most commonly occurring resistance mutation, ROS1 G2032R, and a molecular rationale for the selectivity of NVL-520 for ROS1 over the structurally-related TRK family. TRK inhibition in the CNS by approved or investigational ROS1 TKIs has been associated with neurological adverse events that can be dose limiting. Extensive preclinical characterization of the activity and selectivity of NVL-520 is presented, spanning biochemical and cellular assays, in vivo xenograft studies, and preclinical assessments of brain penetrance and intracranial activity.

In addition, the paper includes three case studies of patients with ROS1 fusion-positive lung cancers that had relapsed on or were refractory to a range of ROS1 TKIs, and includes patients with tumors that harbored ROS1 G2032R or had intracranial metastases. NVL-520 elicited tumor responses in the patients with no observed neurological toxicities. These findings support the potential for NVL-520 to treat these patient populations while also enhancing tolerability through improved selectivity for ROS1.

"At Nuvalent, we aim to solve for multiple, and at times competing, challenges in structure-based drug design with the goal to advance novel therapeutics with the potential for best-in-class activity against recalcitrant targets. This publication in Cancer Discovery provides insight into our focused approach to the discovery of NVL-520 and additional support for the potential achievement of our design goals through comprehensive biochemical and cellular profiling, evaluation across diverse ROS1-fusion driven preclinical models, and patient case studies, said Joshua Horan, Ph.D., Vice President, Chemistry at Nuvalent. "We are grateful to our collaborators for their contributions to this paper and to the continued advancement of NVL-520."

Initial data from the Phase 1 dose-escalation portion of the trial were presented during the "New Drugs on the Horizon" plenary session at the 2022 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium. The ARROS-1 trial is continuing to enroll patients in the Phase 1 portion of the study and is focused on further characterizing the safety profile of NVL-520, its pharmacokinetic profile, and determining the recommended Phase 2 dose.

About NVL-520

NVL-520 is a novel brain-penetrant ROS1-selective inhibitor designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with the prevalent G2032R resistance mutation and those with the S1986Y/F, L2026M, or D2033N resistance mutations. NVL-520 has been optimized for brain penetrance to potentially improve treatment options for patients with brain metastases. NVL-520 has been observed in preclinical studies to selectively inhibit wild-type ROS1 and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and drive more durable responses for patients. NVL-520 is currently being investigated in the ARROS-1 study (NCT05118789), a first-in-human Phase 1/2 clinical trial for patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors.