On May 1, 2023 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported consolidated financial results for the first quarter ended March 31, 2023 and reiterated full year 2023 financial guidance (Press release, Vertex Pharmaceuticals, MAY 1, 2023, View Source [SID1234630788]).

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"Vertex delivered a strong start to 2023, with outstanding execution across our business. We continue to reach more patients globally with our cystic fibrosis medicines and progress our broad and diverse pipeline, most notably completing the rolling BLA submissions for exa-cel in the U.S.," said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex. "Over the course of this year, we look forward to continuing to expand our leadership in CF; preparing for near-term launches, including exa-cel; and advancing multiple potentially transformative medicines through mid- and late-stage clinical trials."

First Quarter 2023 Results
Product revenue increased 13% to $2.37 billion compared to the first quarter of 2022, primarily driven by the strong uptake of TRIKAFTA/KAFTRIO in multiple countries internationally and continued performance of TRIKAFTA in the U.S. Net product revenue in the first quarter of 2023 increased 3% to $1.40 billion in the U.S. and increased 33% to $971 million outside the U.S., compared to the first quarter of 2022.
Combined GAAP and Non-GAAP R&D, Acquired IPR&D and SG&A expenses were $1.3 billion and $1.2 billion, respectively, compared to $818 million and $687 million, respectively, in the first quarter of 2022. The increases were due to higher acquired IPR&D expenses, increased investment in support of multiple programs that have advanced in mid- and late-stage clinical development, and the costs to support launches of Vertex’s therapies globally.
GAAP effective tax rate was 21.5% compared to 20.2% for the first quarter of 2022.
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Non-GAAP effective tax rate was 21.3% compared to 21.5% for the first quarter of 2022. Please refer to Note 1 for further details on our GAAP to Non-GAAP tax adjustments.
GAAP and Non-GAAP net income decreased by 8% and 12%, respectively, compared to the first quarter of 2022, primarily driven by higher acquired IPR&D expenses, increased investment in our mid- and late-stage clinical pipeline, and the costs to support launches of Vertex’s therapies globally, partially offset by strong revenue growth and increased interest income.
Cash, cash equivalents and total marketable securities as of March 31, 2023 were $11.5 billion, compared to $10.9 billion as of December 31, 2022. The increase was primarily driven by strong revenue growth and operating cash flow, partially offset by our upfront payments to Entrada Therapeutics, CRISPR Therapeutics and other collaboration partners, repurchases of our common stock pursuant to our share repurchase program, and income tax payments.

Full Year 2023 Financial Guidance
Vertex today reiterated its full year 2023 financial guidance, including CF product revenue guidance of $9.55 to $9.7 billion. Vertex’s CF product revenue guidance includes expectations in the U.S. for continued performance of TRIKAFTA in ages 6+ and the launch of TRIKAFTA in the 2-5 age group, as well as continued uptake of KAFTRIO/TRIKAFTA in ages 6+ in countries outside the U.S., including those with recent reimbursement agreements. This guidance includes an approximately 150-basis-point negative impact from changes in foreign currency rates, inclusive of our foreign exchange risk management program.
Vertex’s financial guidance is summarized below:
Current FY 2023 Previous FY 2023
CF product revenues Unchanged $9.55 to $9.7 billion
Combined GAAP R&D, Acquired IPR&D and SG&A expenses (2) Unchanged $4.35 to $4.6 billion
Combined Non-GAAP R&D, Acquired IPR&D and SG&A expenses (2) Unchanged $3.9 to $4.0 billion
Non-GAAP effective tax rate Unchanged 21% to 22%

Key Business Highlights
Cystic Fibrosis (CF) Marketed Products
Vertex anticipates the number of CF patients taking our medicines will continue to grow, including through new approvals and reimbursement for the treatment of younger patients. Recent progress includes:
•Vertex received approval from the U.S. Food and Drug Administration (FDA) for the use of TRIKAFTA in children 2 to 5 years of age with at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or a mutation in the CFTR gene that is responsive to TRIKAFTA. With this approval, approximately 900 children are newly eligible for TRIKAFTA. Vertex has also completed regulatory submissions with the European Medicines Agency (EMA), the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom, Health Canada, and the Therapeutic Goods Administration (TGA) in Australia for the use of KAFTRIO/TRIKAFTA in children 2 to 5 years of age.
•Vertex received a positive opinion from the EMA Committee for Medicinal Products for Human Use (CHMP) for the use of ORKAMBI in children 1 to <2 years of age with two copies of the F508del mutation in the CFTR gene. If this label extension is approved by the European Commission, nearly 300 children with CF will be eligible for the first time for a medicine to treat the underlying cause of their disease.
•Vertex has also submitted an sNDA to the FDA and Marketing Authorization Applications (MAAs) to the EMA, MHRA, and Health Canada for the use of KALYDECO in children from 1 month to <4 months of age. The FDA granted Priority Review designation and assigned a PDUFA date of May 3, 2023.
Potential Near-Term Launch Opportunities
Vertex is preparing for the following near-term potential new product launches:

•Exagamglogene autotemcel (exa-cel), formerly known as CTX001, in severe sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT):

◦Vertex completed the rolling submission of its biologics licensing applications (BLAs) in the U.S. The BLAs include requests for Priority Review, which if granted, would shorten the FDA’s review of the application to eight months from the time of submission versus a standard review timeline of 12 months. In the U.S., exa-cel has been granted Fast Track, Regenerative Medicine Advanced Therapy (RMAT), Orphan Drug and Rare Pediatric Disease designations.
◦In December 2022, Vertex completed regulatory submissions for exa-cel with the EMA and MHRA in the EU and the U.K., respectively. Both the EMA and the MHRA have validated the MAAs, indicating acceptance of the marketing applications and initiation of the review. Exa-cel has been granted Priority Medicines (PRIME) and Orphan Drug designation in the EU. In the U.K., exa-cel has been granted an Innovation Passport under the Innovative Licensing and Access Pathway (ILAP) from the MHRA.

•Vanzacaftor/tezacaftor/deutivacaftor, the next-in-class triple combination, in cystic fibrosis: In the fourth quarter of 2022, Vertex completed enrollment in the pivotal SKYLINE 102 and SKYLINE 103 trials, which evaluate the efficacy and safety of vanzacaftor/tezacaftor/deutivacaftor relative to TRIKAFTA in patients with CF 12 years of age and older. Vertex expects to complete the SKYLINE studies by the end of 2023. In parallel, Vertex has initiated a study of vanzacaftor/tezacaftor/deutivacaftor in children with CF 6 to 11 years of age, known as the RIDGELINE study, and the company also expects to complete this study by the end of 2023.
•VX-548 in acute pain: Vertex continues to enroll the Phase 3 pivotal program for its lead compound, VX-548, for the treatment of moderate to severe acute pain and expects to complete the pivotal program in late 2023 or early 2024. VX-548 has been granted Breakthrough Therapy and Fast Track designations in the U.S. for moderate to severe acute pain.
R&D Pipeline
Vertex is delivering on a diversified pipeline of potentially transformative small molecule, mRNA, cell and genetic therapies aimed at serious diseases. Recent and anticipated progress for programs in clinical development is summarized below.
Cystic Fibrosis
Vertex continues to pursue next-in-class, small molecule CFTR modulator therapies as well as an mRNA therapy for the approximately 5,000 patients who cannot benefit from CFTR modulators alone.
•Vertex is developing VX-522, a CFTR mRNA therapeutic, in collaboration with Moderna. The goal of this therapy is to treat the underlying cause of CF by programming cells in the lungs to produce functional CFTR protein, and it is aimed at the treatment of the approximately 5,000 people with CF who do not produce any CFTR protein. Vertex has initiated a single ascending dose (SAD) clinical trial for VX-522 in people with CF, which is active and enrolling patients at multiple sites. Vertex expects to complete the SAD and initiate a multiple ascending dose (MAD) study in 2023. In the U.S., the FDA has granted Fast Track designation for VX-522.

Beta Thalassemia and Sickle Cell Disease

Exa-cel is a non-viral ex vivo CRISPR gene-editing therapy, which is being developed as a potential functional cure for TDT and SCD. Vertex is developing exa-cel in collaboration with CRISPR Therapeutics.
•Dosing in the Phase 1/2/3 CLIMB-111 and CLIMB-121 studies continues, as does the CLIMB-131 long-term follow-up study in patients 12 years of age and older.
•Two additional Phase 3 studies of exa-cel continue to enroll patients 5 to 11 years of age with TDT or SCD.
Neuropathic Pain (NaV1.8)
Vertex has discovered multiple selective small molecule inhibitors of NaV1.8 with the objective of creating a new class of pain medicines that have the potential to provide effective pain relief, without the limitations of opioids and other currently available medicines.
•Vertex continues to enroll and dose patients in a Phase 2 dose-ranging study of VX-548 in patients with diabetic peripheral neuropathy, a common form of peripheral neuropathic pain.
•Vertex expects to complete this study in late 2023 or early 2024.
APOL1-Mediated Kidney Disease (AMKD)
Vertex has discovered multiple oral, small molecule inhibitors of APOL1 function, pioneering a new class of medicines that target an underlying genetic driver of kidney disease.
•In March, the New England Journal of Medicine published results from preclinical studies and a Phase 2 study evaluating the efficacy and safety of inaxaplin (VX-147) on top of standard-of-care in people with focal segmental glomerulosclerosis (FSGS) and two APOL1 variants, a form of AMKD. The results from the Phase 2 study of inaxaplin demonstrated a statistically significant and clinically meaningful mean reduction in proteinuria of 47.6% at 13 weeks compared to baseline. Inaxaplin was generally well tolerated in the study.
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•Vertex continues to enroll and dose patients in the pivotal program for inaxaplin, a single Phase 2/3 clinical trial in patients with AMKD, and expects to complete the Phase 2B dose-ranging portion of the study in 2023.
•Inaxaplin was granted Breakthrough Therapy designation by the FDA for FSGS, as well as Orphan Drug and PRIME designations by the EMA for AMKD.

Type 1 Diabetes (T1D)
Vertex is evaluating cell therapies using stem-cell derived, fully differentiated, insulin-producing islet cells to replace the endogenous insulin-producing islet cells that are destroyed in people with T1D, with the goal of developing a potential functional cure for this disease. Vertex has three programs that use these fully differentiated cells.
1.VX-880, fully differentiated cells with standard immunosuppression: Vertex has completed enrollment and dosing in Part B of the Phase 1/2 study of VX-880. Vertex expects to present updated clinical data, including data from more patients and with longer duration of follow-up from the VX-880 study at scientific congresses in 2023, including the American Diabetes Association Scientific Sessions in June. Next, Vertex intends to begin Part C of the study with concurrent dosing. In March 2023, VX-880 was granted PRIME designation by the EMA.
2.VX-264, fully differentiated cells encapsulated in immunoprotective device: The Investigational New Drug (IND) application in the U.S. and the Clinical Trial Application (CTA) in Canada for VX-264, the cells plus device program, have been cleared, and Vertex plans to begin enrollment and dosing in a Phase 1/2 clinical trial in the near term.
3.Edited fully differentiated cells: Vertex’s hypoimmune cell research program continues to progress.
In addition, a Phase 1/2 study of VCTX-211, a hypoimmune cell program using ViaCyte cells that originated under the CRISPR Therapeutics and ViaCyte collaboration, is active and enrolling patients.
Alpha-1 Antitrypsin Deficiency
Vertex is working to address the underlying genetic cause of alpha-1 antitrypsin (AAT) deficiency by developing novel small molecule correctors of Z-AAT protein folding, with a goal of increasing the secretion of functional AAT into the blood and addressing both the lung and the liver aspects of AAT deficiency.
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•Vertex initiated a 48-week Phase 2 study of VX-864, a first-generation AAT corrector, to assess the impact of longer-term treatment on polymer clearance from the liver, as well as the resultant levels of functional AAT (fAAT) in the plasma. This Phase 2 trial continues to enroll and dose patients.
•Additionally, Vertex continues to enroll and dose healthy volunteers with VX-634, a follow-on small molecule AAT corrector. VX-634 is the first in a series of next-wave investigational molecules with significantly improved potency and drug-like properties compared to previous Vertex AAT correctors.
Additional Earlier Stage R&D Programs
Consistent with its overall strategy, Vertex takes a portfolio approach to all of its programs, with additional assets in CF, SCD, TDT, pain, AMKD, T1D and AATD in earlier stages of development.
Vertex is also advancing preclinical assets in new disease areas, such as Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1). Additionally, Vertex is working on preclinical molecules with the potential to expand our leadership in existing disease areas, including assets targeting gentler conditioning for exa-cel and NaV1.7 in pain.
Investments in External Innovation
Consistent with its strategy to develop transformative medicines for serious diseases, in the first quarter of 2023, Vertex announced a new licensing agreement for the use of CRISPR Therapeutics’ gene editing technology, known as CRISPR/Cas9, to accelerate the development of Vertex’s hypoimmune cell therapies for T1D. Under this agreement, Vertex made an upfront payment of $100 million to CRISPR in the first quarter of 2023.
In addition, the previously announced global research collaboration with Entrada Therapeutics, focused on therapeutics for DM1, has closed. Under the terms of the agreement, upon closing, Vertex made an upfront payment of approximately $225 million to Entrada, as well as an equity investment of approximately $25 million.
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Non-GAAP Financial Measures
In this press release, Vertex’s financial results and financial guidance are provided in accordance with accounting principles generally accepted in the United States (GAAP) and using certain non-GAAP financial measures. In particular, non-GAAP financial results and guidance exclude from Vertex’s pre-tax income (i) stock-based compensation expense, (ii) gains or losses related to the fair value of the company’s strategic investments, (iii) increases or decreases in the fair value of contingent consideration, (iv) acquisition-related costs, and (v) other adjustments. The company’s non-GAAP financial results also exclude from its provision for income taxes the estimated tax impact related to its non-GAAP adjustments to pre-tax income described above and certain discrete items. These results should not be viewed as a substitute for the company’s GAAP results and are provided as a complement to results provided in accordance with GAAP. Management believes these non-GAAP financial measures help indicate underlying trends in the company’s business, are important in comparing current results with prior period results and provide additional information regarding the company’s financial position that the company believes is helpful to an understanding of its ongoing business. Management also uses these non-GAAP financial measures to establish budgets and operational goals that are communicated internally and externally, to manage the company’s business and to evaluate its performance. The company’s calculation of non-GAAP financial measures likely differs from the calculations used by other companies. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the attached financial information.

The company provides guidance regarding combined R&D, Acquired IPR&D and SG&A expenses and effective tax rate on a non-GAAP basis. Unless otherwise noted, the guidance regarding combined GAAP and non-GAAP R&D, Acquired IPR&D and SG&A expenses does not include estimates associated with any potential future business development transactions, including collaborations, asset acquisitions and/or licensing of third-party intellectual property rights. The company does not provide guidance regarding its GAAP effective tax rate because it is unable to forecast with reasonable certainty the impact of excess tax benefits related to stock-based compensation and the possibility of certain discrete items, which could be material.

On May 1, 2023 Veracyte, Inc. (Nasdaq: VCYT) reported that three abstracts focused on the company’s genomic tests for interstitial lung disease (Envisia Genomic Classifier) and lung cancer (Percepta Nasal Swab) will be presented at the American Thoracic Society (ATS) 2023 International Conference (Press release, Veracyte, MAY 1, 2023, View Source [SID1234630787]). The meeting will take place May 19-24 in Washington, D.C.

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"We look forward to these new data being shared at ATS 2023, which explore the impact of our Envisia Genomic Classifier on diagnosis and treatment decisions for patients with interstitial lung diseases, as well as in identifying patients whose ILD is likely to progress," said Bill Bulman, M.D., Veracyte’s medical director for Pulmonology. "In addition, expanded preliminary data will be presented regarding use of the Percepta Nasal Swab test on potentially cancerous lung nodules found on CT scans."

The following abstracts will be presented at the ATS 2023 International Conference:

Title: Genomic Classifier for Usual Interstitial Pneumonia Predicts Progression in Fibrotic Lung Disease Across a Range of Clinical Diagnoses
Presenter: Ganesh Raghu, M.D., University of Washington
Session: A102 – Poster 822
Format: Poster Discussion Session
Date/Time: May 21, 2023, 2:15 p.m. – 4:15 p.m. ET
Location: Walter E. Washington Convention Center, Room 209 A-C (Level 2)

Title: The Impact of Genomic Classifier in Patients With Undiagnosed Interstitial Lung Disease
Presenter: Diana Espinoza Barrera, M.D., Tulane University
Session: C39 – Poster P555
Format: Thematic Poster Session
Date/Time: May 23, 2023, 11:30 a.m. – 1:15 p.m. ET
Location: Walter E. Washington Convention Center, Area E, Hall C (Lower Level)

Title: Demonstrating Clinical Utility for a Nasal Genomic Classifier for Lung Nodules: Addressing the Clinical Trial Learning Curve With a Familiarization Phase
Presenter: Farah Madhani-Lovely, M.D., Renown Health
Session: D31 – Poster 317
Format: Poster Discussion Session
Date/Time: May 24, 2023, 8:00 a.m. – 10:00 a.m. ET
Location: Walter E. Washington Convention Center, Room 144 A-C (Street Level)

On May 1, 2023 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported the results of a sub-analysis from the first and largest post-commercial utilization review of JELMYTO (mitomycin) for pyelocalyceal solution presented today at the American Urological Association Meeting 2023 in Chicago, IL (Press release, UroGen Pharma, MAY 1, 2023, https://investors.urogen.com/news-releases/news-release-details/first-study-evaluate-jelmytor-use-post-complete-endoscopic [SID1234630786]). The study titled, "Efficacy and Safety of Mitomycin Gel (UGN-101) as an Adjuvant Therapy After Complete Endoscopic Management of Upper Tract Urothelial Carcinoma Early Experience with UGN-101 for the Treatment of Upper Tract Urothelial Cancer – A Multi-Center Evaluation of Practice Patterns and Outcomes," is also published in the May issue of The Journal of Urology.

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"We are pleased to see that the growing body of real-world evidence supports the use of JELMYTO in a diverse LG-UTUC population," said Mark Schoenberg, Chief Medical Officer, UroGen. "JELMYTO is a versatile therapy for clinicians trying to manage high recurrence rates of LG-UTUC."

In the publication, the authors note that UTUC disease recurrence is often detected at the first ureteroscopic evaluation after endoscopic ablation only. Early failure is a drawback for endoscopic ablation alone, which occurs in 40-50% of UTUC patients by three months. The authors report that this may be due to incomplete resection or ablation of the primary tumor for which post-ablation therapy is designed to treat.

UTUC patients in this retrospective study who underwent complete endoscopic ablation followed by JELMYTO were more likely to be disease-free at first endoscopic evaluation than those who underwent chemoablation alone (69% vs. 40%), whereas in the Phase 3 OLYMPUS study of JELMYTO, LG-UTUC patients in the primary chemoablation setting achieved a 59% complete response rate at first endoscopic evaluation.

Response at primary endoscopic evaluation was defined as no visual tumor or negative biopsy. The rate of ureteral stenosis for those in this study who underwent complete endoscopic ablation followed by JELMYTO treatment was 23%. Ureteral stenosis was defined as a condition requiring ureteral stent or nephrostomy, or that would typically warrant stent or nephrostomy. In their publication the authors noted that longer follow-up rate is needed to determine if JELMYTO after complete endoscopic ablation of UTUC will lead to durable disease-free interval.

The limitations of this study include the retrospective design, lack of a control group, the lack of a centralized pathology review, and standardized clinicopathologic assessment. Other limitations include: the assumption that complete endoscopic ablation resulted in complete tumor destruction, though data from early second-look ureteroscopy after endoscopic ablation show in-field recurrences suggesting incomplete tumor ablation; follow-up was short and the interval between surveillance ureteroscopy after initial post-treatment evaluation of surveillance was not uniform amongst centers, which may lead to bias in survivorship data; and tumor size prior to endoscopic ablation was not accounted for in this study and may have biased patients with lower tumor volume to undergo complete endoscopic ablation.

To further explore the full potential of JELMYTO for the treatment of patients with UTUC, investigators are in the process of enrolling the prospective and retrospective uTRACT Registry to capture data in a large-scale, standardized manner to report further on patient outcomes following JELMYTO treatment including longitudinal follow-up.

About UTUC

Approximately 5-7% of urothelial cancer occurs in the upper lining of the kidney, called the calyx and renal pelvis. It could also occur in one or both of the ureter(s), the tubes that lead from the kidneys to the bladder. Cancer in the renal pelvis or ureter(s) is called upper tract. LG-UTUC is usually not very aggressive and is slow to spread but has a high recurrence rate. High-grade UTUC can be more aggressive. It may spread to other parts of the urinary tract, or to other parts of the body.

JELMYTO is approved for the treatment of adults with LG-UTUC, a rare disease managed by endoscopic methods and radical nephroureterectomy. Endoscopic resection and laser ablation attempt to preserve the kidney, though there is a high risk of recurrence that may eventually necessitate removal of the kidney. Although kidney removal is the gold standard for treatment of high-grade UTUC, it may be over-treatment in LG-UTUC, as kidney removal offers similar five-year survival as kidney-sparing procedures but is associated with significant morbidity. JELMYTO is efficacious as a primary chemoablative therapy in patients with LG-UTUC.

About JELMYTO

JELMYTO (mitomycin) for pyelocalyceal solution is a mitomycin-containing reverse thermal gel containing 4 mg mitomycin per mL gel indicated for primary chemoablative treatment of LG-UTUC in adults. It is recommended for primary treatment of biopsy-proven LG-UTUC in patients deemed appropriate candidates for renal-sparing therapy. JELMYTO is a viscous liquid when cooled and becomes a semi-solid gel at body temperature. The drug slowly dissolves over four to six hours after instillation and is removed from the urinary tract by normal urine flow and voiding. It is approved for administration in a retrograde manner via ureteral catheter or antegrade through nephrostomy tube. The delivery system allows the initial liquid to coat and conform to the upper urinary tract anatomy. The eventual semisolid gel allows for chemoablative therapy to remain in the collecting system for four to six hours without immediately being diluted or washed away by urine flow.

APPROVED USE FOR JELMYTO

JELMYTO is a prescription medicine used to treat adults with a type of cancer of the lining of the upper urinary tract including the kidney called low-grade Upper Tract Urothelial Cancer (LG-UTUC).

IMPORTANT SAFETY INFORMATION

You should not receive JELMYTO if you have a hole or tear (perforation) of your bladder or upper urinary tract.

Before receiving JELMYTO, tell your healthcare provider about all your medical conditions, including if you:

are pregnant or plan to become pregnant. JELMYTO can harm your unborn baby. You should not become pregnant during treatment with JELMYTO. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with JELMYTO. Females who are able to become pregnant: You should use effective birth control (contraception) during treatment with JELMYTO and for 6 months after the last dose. Males being treated with JELMYTO: If you have a female partner who is able to become pregnant, you should use effective birth control (contraception) during treatment with JELMYTO and for 3 months after the last dose.
are breastfeeding or plan to breastfeed. It is not known if JELMYTO passes into your breast milk. Do not breastfeed during treatment with JELMYTO and for 1 week after the last dose.
Tell your healthcare provider if you take water pills (diuretic).
How will I receive JELMYTO?

Your healthcare provider will tell you to take a medicine called sodium bicarbonate before each JELMYTO treatment.
You will receive your JELMYTO dose from your healthcare provider 1 time a week for 6 weeks. It is important that you receive all 6 doses of JELMYTO according to your healthcare provider’s instructions. If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. Your healthcare provider may recommend up to an additional 11 monthly doses.
JELMYTO is given to your kidney through a tube called a catheter.
During treatment with JELMYTO, your healthcare provider may tell you to take additional medicines or change how you take your current medicines.
After receiving JELMYTO:

JELMYTO may cause your urine color to change to a violet to blue color. Avoid contact between your skin and urine for at least 6 hours.
To urinate, males and females should sit on a toilet and flush the toilet several times after you use it. After going to the bathroom, wash your hands, your inner thighs, and genital area well with soap and water.
Clothing that comes in contact with urine should be washed right away and washed separately from other clothing.
JELMYTO may cause serious side effects, including:

Swelling and narrowing of the tube that carries urine from the kidney to the bladder (ureteric obstruction). If you develop swelling and narrowing, and to protect your kidney from damage, your healthcare provider may recommend the placement of a small plastic tube (stent) in the ureter to help the kidney drain. Tell your healthcare provider right away if you develop side pain or fever during treatment with JELMYTO.
Bone marrow problems. JELMYTO can affect your bone marrow and can cause a decrease in your white blood cell, red blood cell, and platelet counts. Your healthcare provider will do blood tests prior to each treatment to check your blood cell counts during treatment with JELMYTO. Your healthcare provider may need to temporarily or permanently stop JELMYTO if you develop bone marrow problems during treatment with JELMYTO.
The most common side effects of JELMYTO include: urinary tract infection, blood in your urine, side pain, nausea, trouble with urination, kidney problems, vomiting, tiredness, stomach (abdomen) pain.

You are encouraged to report negative side effects of prescription drugs to the U.S. Food and Drug Administration. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to UroGen Pharma at 1-855-987-6436.

Please click here for JELMYTO Full Prescribing Information, including the Patient Information, for additional information and here for the Nephrostomy Administration Guide.

On May 1, 2023 TG Therapeutics, Inc. (NASDAQ: TGTX) reported its financial results for the first quarter ended March 31, 2023, along with recent company developments, and a business outlook for 2023 (Press release, TG Therapeutics, MAY 1, 2023, View Source [SID1234630785]).

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Michael S. Weiss, the Company’s Chairman and Chief Executive Officer, stated, "2023 is off to an exciting start for us at TG. With the U.S. approval and commercial launch of BRIUMVI, we are excited to be able to offer patients the first and only anti-CD20 monoclonal antibody approved for relapsing forms of multiple sclerosis that can be administered in a one-hour infusion, twice a year, following the starting dose, which are some of the attributes that support our belief in BRIUMVI’s best-in-class potential in multiple sclerosis. It’s gratifying to see that the pre-launch enthusiasm for BRIUMVI is translating into the commercial setting and the feedback we have heard from both healthcare providers and patients has been highly encouraging." Mr. Weiss continued, "Overall, I believe our team is doing a fantastic job and I am pleased to share that in our first partial quarter, essentially two months of commercial availability, we generated approximately $8 million in net sales. The early launch of BRIUMVI has exceeded our internal expectations, and we believe the momentum will continue to build throughout the year."

Recent Highlights & Developments for BRIUMVI(ublituximab-xiiy)

Received U.S. Food and Drug Administration (FDA) approval of BRIUMVI, for the treatment of relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults, on December 28, 2022.
Commercially launched BRIUMVI in the U.S. on January 26, 2023, making it available for patients and physicians.
Achieved $7.8M in BRIUMVI net sales for the first partial launch quarter, and have payor coverage policies in place for over 50% of covered lives across the U.S.
Over 400 BRIUMVI prescriptions in the first partial quarter from more than 165 healthcare providers at more than 125 centers.
Received notification that the U.S. Centers for Medicare & Medicaid Services (CMS) has issued a permanent J-Code (J2329) for BRIUMVI, which will become effective July 1, 2023.
Received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommending the approval of BRIUMVI for the treatment of adult RMS patients with active disease defined by clinical or imaging features.
Presented additional data, including new analyses, from the ULTIMATE I and II Phase 3 trials at the 2023 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) annual forum and the American Academy of Neurology (AAN) 75th Annual Meeting.
Key Objectives for 2023

Continue to build upon the commercial launch of BRIUMVI in RMS
Obtain broad payor coverage for BRIUMVI
Continue to present additional data from the ULTIMATE I & II Phase 3 trials of BRIUMVI in RMS
Financial Results for the Three Months Ended March 31, 2023

Product Revenue, Net: Product revenue, net was approximately $7.8 million for the three months ended March 31, 2023, compared to $2.0 million for the three months ended March 31, 2022. Product revenue, net for the three months ended March 31, 2023, consisted of net product sales of BRIUMVI in the United States, which was commercially launched in late January 2023. Product revenue, net for the three months ended March 31, 2022, consisted of net product sales of UKONIQ (umbralisib), which was withdrawn from the U.S. market in May of 2022.
R&D Expenses: Total research and development (R&D) expense was $15.9 million for the three months ended March 31, 2023, compared to $48.0 million for the three months ended March 31, 2022. The decrease in R&D expense was primarily attributable to reduced manufacturing expense, clinical trial related expenses, and decreased headcount during the three months ended March 31, 2023. Prior to the approval of BRIUMVI, manufacturing costs pertaining to BRIUMVI were expensed to R&D expense in the period incurred, and following approval are reflected in inventory.
SG&A Expenses: Total selling, general and administrative (SG&A) expense was $28.1 million for the three months ended March 31, 2023, compared to $20.6 million for the three months ended March 31, 2022. The increase was due primarily to approximately $5.2 million in non-cash compensation SG&A expenses incurred during the first quarter of 2023, and other costs, including personnel, associated with the approval of BRIUMVI during the three months ended March 31, 2023.
Net Loss: Net loss was $39.2 million for the three months ended March 31, 2023, compared to $69.0 million for the three months ended March 31, 2022. Excluding non-cash compensation, the net loss for the three months ended March 31, 2023, was approximately $32.4 million, compared to a net loss of $66.9 million for the three months ended March 31, 2022.
Cash Position and Financial Guidance: Cash, cash equivalents and investment securities were $139.7 million as of March 31, 2023. We anticipate that our cash, cash equivalents and investment securities as of March 31, 2023, combined with $20.0 million of available capacity under our existing term loan facility and projected revenues, will be sufficient to fund our planned operations into mid-2024.
CONFERENCE CALL INFORMATION
The Company will host a conference call today, May 1, 2023, at 8:30 AM ET, to discuss the Company’s financial results from the first quarter, ended March 31, 2023, and provide a business outlook for the remainder of 2023.

To participate in the conference call, please call 1-877-407-8029 (U.S.), 1-201-689-8029 (outside the U.S.), Conference Title: TG Therapeutics. A live audio webcast will be available on the Events page, located within the Investors & Media section, of the Company’s website at View Source An audio recording of the conference call will also be available for a period of 30 days after the call.

ABOUT BRIUMVI (ublituximab-xiiy) 150 mg/6 mL Injection for IV
BRIUMVI is a novel monoclonal antibody that targets a unique epitope on CD20-expressing B-cells. Targeting CD20 using monoclonal antibodies has proven to be an important therapeutic approach for the management of autoimmune disorders, such as RMS. BRIUMVI is uniquely designed to lack certain sugar molecules normally expressed on the antibody. Removal of these sugar molecules, a process called glycoengineering, allows for efficient B-cell depletion at low doses.

BRIUMVI is indicated for the treatment of adults with relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

A list of authorized specialty distributors can be found at www.briumvi.com.

IMPORTANT SAFETY INFORMATION
Contraindications: BRIUMVI is contraindicated in patients with:

Active HBV infection
A history of life-threatening infusion reaction to BRIUMVI
WARNINGS AND PRECAUTIONS

Infusion Reactions: BRIUMVI can cause infusion reactions, which can include pyrexia, chills, headache, influenza-like illness, tachycardia, nausea, throat irritation, erythema, and an anaphylactic reaction. In MS clinical trials, the incidence of infusion reactions in BRIUMVI-treated patients who received infusion reaction-limiting premedication prior to each infusion was 48%, with the highest incidence within 24 hours of the first infusion. 0.6% of BRIUMVI-treated patients experienced infusion reactions that were serious, some requiring hospitalization.

Observe treated patients for infusion reactions during the infusion and for at least one hour after the completion of the first two infusions unless infusion reaction and/or hypersensitivity has been observed in association with the current or any prior infusion. Inform patients that infusion reactions can occur up to 24 hours after the infusion. Administer the recommended pre-medication to reduce the frequency and severity of infusion reactions. If life-threatening, stop the infusion immediately, permanently discontinue BRIUMVI, and administer appropriate supportive treatment. Less severe infusion reactions may involve temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment.

Infections: Serious, life-threatening or fatal, bacterial and viral infections have been reported in BRIUMVI-treated patients. In MS clinical trials, the overall rate of infections in BRIUMVI-treated patients was 56% compared to 54% in teriflunomide-treated patients. The rate of serious infections was 5% compared to 3% respectively. There were 3 infection-related deaths in BRIUMVI-treated patients. The most common infections in BRIUMVI-treated patients included upper respiratory tract infection (45%) and urinary tract infection (10%). Delay BRIUMVI administration in patients with an active infection until the infection is resolved.

Consider the potential for increased immunosuppressive effects when initiating BRIUMVI after immunosuppressive therapy or initiating an immunosuppressive therapy after BRIUMVI.

Hepatitis B Virus (HBV) Reactivation: HBV reactivation occurred in an MS patient treated with BRIUMVI in clinical trials. Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with anti-CD20 antibodies. Perform HBV screening in all patients before initiation of treatment with BRIUMVI. Do not start treatment with BRIUMVI in patients with active HBV confirmed by positive results for HBsAg and anti-HB tests. For patients who are negative for surface antigen [HBsAg] and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult a liver disease expert before starting and during treatment.

Progressive Multifocal Leukoencephalopathy (PML): Although no cases of PML have occurred in BRIUMVI-treated MS patients, JCV infection resulting in PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies.

If PML is suspected, withhold BRIUMVI and perform an appropriate diagnostic evaluation. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.

MRI findings may be apparent before clinical signs or symptoms; monitoring for signs consistent with PML may be useful. Further investigate suspicious findings to allow for an early diagnosis of PML, if present. Following discontinuation of another MS medication associated with PML, lower PML-related mortality and morbidity have been reported in patients who were initially asymptomatic at diagnosis compared to patients who had characteristic clinical signs and symptoms at diagnosis.

If PML is confirmed, treatment with BRIUMVI should be discontinued.

Vaccinations: Administer all immunizations according to immunization guidelines: for live or live-attenuated vaccines at least 4 weeks and, whenever possible at least 2 weeks prior to initiation of BRIUMVI for non-live vaccines. BRIUMVI may interfere with the effectiveness of non-live vaccines. The safety of immunization with live or live-attenuated vaccines during or following administration of BRIUMVI has not been studied. Vaccination with live virus vaccines is not recommended during treatment and until B-cell repletion.

Vaccination of Infants Born to Mothers Treated with BRIUMVI During Pregnancy: In infants of mothers exposed to BRIUMVI during pregnancy, assess B-cell counts prior to administration of live or live-attenuated vaccines as measured by CD19+ B-cells. Depletion of B-cells in these infants may increase the risks from live or live-attenuated vaccines. Inactivated or non-live vaccines may be administered prior to B-cell recovery. Assessment of vaccine immune responses, including consultation with a qualified specialist, should be considered to determine whether a protective immune response was mounted.

Fetal Risk: Based on data from animal studies, BRIUMVI may cause fetal harm when administered to a pregnant woman. Transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 B-cell depleting antibodies during pregnancy. A pregnancy test is recommended in females of reproductive potential prior to each infusion. Advise females of reproductive potential to use effective contraception during BRIUMVI treatment and for 6 months after the last dose.

Reduction in Immunoglobulins: As expected with any B-cell depleting therapy, decreased immunoglobulin levels were observed. Decrease in immunoglobulin M (IgM) was reported in 0.6% of BRIUMVI-treated patients compared to none of the patients treated with teriflunomide in RMS clinical trials. Monitor the levels of quantitative serum immunoglobulins during treatment, especially in patients with opportunistic or recurrent infections, and after discontinuation of therapy until B-cell repletion. Consider discontinuing BRIUMVI therapy if a patient with low immunoglobulins develops a serious opportunistic infection or recurrent infections, or if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins.

Most Common Adverse Reactions: The most common adverse reactions in RMS trials (incidence of at least 10%) were infusion reactions and upper respiratory tract infections.

Physicians, pharmacists, or other healthcare professionals with questions about BRIUMVI should visit www.briumvi.com.

ABOUT BRIUMVI PATIENT SUPPORT
BRIUMVI Patient Support is a flexible program designed by TG Therapeutics to support patients through their treatment journey in a way that works best for them. More information about the BRIUMVI Patient Support program can be accessed at www.briumvipatientsupport.com.

ABOUT MULTIPLE SCLEROSIS
Relapsing multiple sclerosis (RMS) is a chronic demyelinating disease of the central nervous system (CNS) and includes people with relapsing-remitting multiple sclerosis (RRMS) and people with secondary progressive multiple sclerosis (SPMS) who continue to experience relapses. RRMS is the most common form of multiple sclerosis (MS) and is characterized by episodes of new or worsening signs or symptoms (relapses) followed by periods of recovery. It is estimated that nearly 1 million people are living with MS in the United States and approximately 85% are initially diagnosed with RRMS.1,2 The majority of people who are diagnosed with RRMS will eventually transition to SPMS, in which they experience steadily worsening disability over time. Worldwide, more than 2.3 million people have a diagnosis of MS.

On May 1, 2023 Syndax Pharmaceuticals, Inc. (Nasdaq: SNDX), a clinical-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that it will report its first quarter 2023 financial results and provide a business update on Monday, May 8, after the close of the U.S. financial markets (Press release, Syndax, MAY 1, 2023, View Source [SID1234630784]).

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In connection with the earnings release, Syndax’s management will host a conference call and live audio webcast at 4:30 p.m. ET on Monday, May 8, 2023 to discuss the Company’s financial results and provide a business update.

The live audio webcast and accompanying slides may be accessed through the Events & Presentations page in the Investors section of the Company’s website. Alternatively, the conference call may be accessed through the following:

Conference ID: SNDX1Q23
Domestic Dial-in Number: 800-579-2543
International Dial-in Number: 785-424-1789
Live webcast: https://www.veracast.com/webcasts/syndax/events/SNDX1Q23.cfm

For those unable to participate in the conference call or webcast, a replay will be available on the Investors section of the Company’s website at www.syndax.com approximately 24 hours after the conference call and will be available for 90 days following the call.