On August 1, 2023 Aptevo Therapeutics Inc. (NASDAQ:APVO) ("Aptevo" or the "Company"), a clinical stage biotechnology company focused on developing novel immuno-oncology therapeutics, reported that the Company has entered into definitive agreements with healthcare-focused institutional investors for the purchase and sale of 8,064,517 shares of common stock (or common stock equivalents in lieu thereof) at a purchase price of $0.62 per share (Press release, Aptevo Therapeutics, AUG 1, 2023, View Source [SID1234633604]). The Company further agreed to issue to the investors Series A Warrants to purchase up to an aggregate of 8,064,517 shares of common stock and Series B Warrants to purchase up to an aggregate of 8,064,517 shares of common stock. The Series A and Series B Warrants will have an exercise price of $0.62 per share, will be exercisable immediately following the date of issuance and will expire in 2025 and 2028, respectively.

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The closing of the offering is expected to occur on or about August 4, 2023, subject to the satisfaction of customary closing conditions. Gross proceeds from the offering are expected to be approximately $5 million before deducting placement agent fees and other estimated offering expenses. The Company intends to use the net proceeds of this offering for working capital purposes.

A.G.P./Alliance Global Partners is acting as sole placement agent for the offering.

The securities described above are being offered pursuant to a registration statement on Form S-1 (File No. 333-273067) previously filed with the Securities and Exchange Commission (SEC) which became effective on August 1, 2023. The offering is being made only by means of a prospectus forming part of the effective registration statement. Copies of the preliminary prospectus and, when available, copies of the final prospectus, relating to the offering may be obtained on the SEC’s website located at View Source Electronic copies of the final prospectus relating to the offering may be obtained, when available, from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022, or by telephone at (212) 624-2060, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation, or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On August 1, 2023 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported consolidated financial results for the second quarter ended June 30, 2023 and updated its full year 2023 financial guidance (Press release, Vertex Pharmaceuticals, AUG 1, 2023, View Source [SID1234633600]).

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"The second quarter of 2023 marked another period of strong progress across our business. We are reaching more patients globally with our cystic fibrosis medicines, advancing our late-stage clinical programs and making rapid progress across our research and development pipeline of transformative medicines," said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex. "In the second half of the year, we look forward to expanding our leadership in CF; continuing to prepare for several near-term potential launches, starting with exa-cel; and completing major Phase 3 trials including VX-548 in acute pain and the vanzacaftor triple in cystic fibrosis."

Second Quarter 2023 Results
Product revenue increased 14% to $2.49 billion compared to the second 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., including the launch in children with CF 2 to 5 years of age. Net product revenue in the second quarter of 2023 increased 7% to $1.51 billion in the U.S. and increased 26% to $985 million outside the U.S., compared to the second quarter of 2022.
Combined GAAP and Non-GAAP R&D, Acquired IPR&D and SG&A expenses were $1.2 billion and $1.0 billion, respectively, compared to $877 million and $750 million, respectively, in the second quarter of 2022. The increases were due to increased investment in support of multiple programs that have advanced in mid- and late-stage clinical development, increased acquired IPR&D expenses, and the costs to support launches of Vertex’s therapies globally.
GAAP effective tax rate was 21.2% compared to 20.9% for the second quarter of 2022.

Non-GAAP effective tax rate was 21.0% compared to 21.8% for the second quarter of 2022. Please refer to Note 1 for further details on our GAAP to Non-GAAP tax adjustments.
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GAAP and Non-GAAP net income increased by 13% and 9%, respectively, compared to the second quarter of 2022, primarily driven by strong revenue growth and increased interest income partially offset by increased investment in our mid- and late-stage clinical pipeline, increased acquired IPR&D expenses, and the costs to support launches of Vertex’s therapies globally.
Cash, cash equivalents and total marketable securities as of June 30, 2023 were $12.6 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 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 is raising its full year 2023 CF product revenue guidance to $9.7 to $9.8 billion, from $9.55 to $9.7 billion previously. The increase reflects the expected full-year impact of the strong uptake of TRIKAFTA/KAFTRIO in multiple countries internationally and continued performance of TRIKAFTA in the U.S. 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 is also increasing full year 2023 combined GAAP and non-GAAP R&D, Acquired IPR&D and SG&A expense guidance. The increase accounts for higher acquired IPR&D expenses incurred year-to-date, including a $70 million milestone payment to CRISPR Therapeutics.

Vertex’s financial guidance is summarized below:
Current FY 2023 Previous FY 2023
CF product revenues $9.7 to $9.8 billion $9.55 to $9.7 billion
Combined GAAP R&D, Acquired IPR&D and SG&A expenses (2) $4.55 to $4.8 billion $4.35 to $4.6 billion
Combined Non-GAAP R&D, Acquired IPR&D and SG&A expenses (2) $4.1 to $4.2 billion $3.9 to $4.0 billion
Non-GAAP effective tax rate Unchanged 21% to 22%

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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:
•Approval from the European Commission for the use of ORKAMBI in children with CF ages 1 to <2 years old who have two copies of the F508del mutation in the CFTR gene. With this approval, approximately 300 children with CF are eligible for the first time for a medicine that can treat the underlying cause of their disease.
•At the European Cystic Fibrosis Society’s (ECFS) European Cystic Fibrosis Conference in June, Vertex presented interim results from the largest real-world study of TRIKAFTA/KAFTRIO, which showed sustained improvement in lung function, reduction in pulmonary exacerbations frequency and lower rates of lung transplant and death for people with CF.
•Approval from the U.S. Food and Drug Administration (FDA) for the use of KALYDECO in children with CF from 1 month to <4 months of age. This approval represents the first and only CFTR modulator approved for this age group. Vertex also submitted Marketing Authorization Applications (MAAs) to the European Medicines Agency (EMA), the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom, and Health Canada for the use of KALYDECO in children with CF from 1 month to <4 months of age.
•Approval from the 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 eligible for TRIKAFTA for the first time. Vertex also completed regulatory submissions with the EMA, the MHRA, Health Canada, and the Therapeutic Goods Administration in Australia for the use of KAFTRIO/TRIKAFTA in children 2 to 5 years of age.

Potential Near-Term Launch Opportunities
Vertex is preparing for the following near-term potential new product launches:

•Exagamglogene autotemcel (exa-cel) in SCD and TDT: Exa-cel is a precise non-viral ex vivo CRISPR gene-editing therapy, which is being developed in collaboration with CRISPR Therapeutics as a potential functional cure for SCD and TDT.
▪The FDA accepted the Biologics License Applications (BLAs) for exa-cel and assigned Prescription Drug User Fee Act (PDUFA) action dates of December 8, 2023, for SCD and March 30, 2024, for TDT. Exa-cel’s BLA for SCD was granted Priority Review by the
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FDA. The FDA has indicated that they plan to hold an advisory committee meeting for exa-cel. In the U.S., exa-cel has been granted Fast Track, Regenerative Medicine Advanced Therapy (RMAT), Orphan Drug and Rare Pediatric Disease designations.
▪As with the U.S. FDA, reviews of the regulatory filings for exa-cel with the EMA in the EU and the MHRA in the U.K. are well underway. 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 from the MHRA.
▪At the 2023 Annual European Hematology Association (EHA) (Free EHA Whitepaper) Congress in June, Vertex presented positive interim results from the pivotal trials of exa-cel in SCD and TDT as of a September 2022 data cut. Both trials met the primary and key secondary endpoints at pre-specified interim analyses, and the data continue to demonstrate transformative, consistent and durable benefit. The data presented at EHA (Free EHA Whitepaper) were the basis of the EMA and MHRA regulatory filings for exa-cel. Vertex expects to present updated clinical data that served as the basis of the FDA filing at a future medical congress.
▪Dosing in the Phase 1/2/3 CLIMB-111 and CLIMB-121 studies is ongoing, and Vertex continues to enroll and follow patients in the CLIMB-131 long-term follow-up study.

•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. More recently, Vertex also completed enrollment in the RIDGELINE study of vanzacaftor/tezacaftor/deutivacaftor in children with CF 6 to 11 years of age. Vertex expects to complete both the SKYLINE and RIDGELINE studies by the end of 2023 and share the results of these studies in early 2024.

•VX-548 in acute pain: 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 the Phase 3 pivotal program, including two randomized controlled trials in abdominoplasty and bunionectomy and a single arm safety and
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effectiveness trial, for its lead compound, VX-548, for the treatment of moderate to severe acute pain.
▪Vertex expects to complete the pivotal program in late 2023 and share results from these studies in late 2023 or early 2024. In the U.S., VX-548 has been granted Breakthrough Therapy and Fast Track designations 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 is enrolling patients in a single ascending dose (SAD) clinical trial for VX-522, and the Company 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 to VX-522.
•Consistent with its overall strategy, Vertex takes a portfolio approach to all of its programs and is advancing additional CFTR modulators with the goal of bringing more patients to carrier levels of sweat chloride.

Beta Thalassemia and Sickle Cell Disease
•Two global Phase 3 studies of exa-cel continue to enroll and dose patients 5 to 11 years of age with TDT or SCD.
•Additionally, Vertex continues to work on preclinical assets for gentler conditioning for exa-cel, which could broaden the eligible patient population from 32,000 patients to more than 150,000.

Acute and Neuropathic Pain
•The Phase 2 dose-ranging study of VX-548 in patients with diabetic peripheral neuropathy, a common form of peripheral neuropathic pain, has been fully enrolled.
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•Dosing in the Phase 2, 12-week VX-548 study continues, and Vertex expects to complete this study in late 2023 and share results in late 2023 or early 2024.
•Consistent with its overall strategy, Vertex takes a portfolio approach to all of its programs and is advancing additional NaV1.8 inhibitors as well as NaV1.7 inhibitors through research and earlier stages of development for pain.

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.
•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 established proof-of-concept for VX-880 in 2022. In June 2023, Vertex presented positive, updated clinical data from the ongoing VX-880 Phase 1/2 study at the American Diabetes Association Scientific Sessions (ADA). The Phase 1/2 study is designed as a sequential, multi-part clinical trial to evaluate the safety and efficacy of VX-880. In Part A, the first two patients received half the target dose of VX-880 cells. In Part B, patients received the full target dose with staggered dosing. Based on the results from Parts A and B, Vertex has initiated Part C of the study, with concurrent dosing at the full target dose, with trial sites currently active in the U.S., Canada, Norway, Switzerland, the Netherlands and France.
In the data presented at ADA, all patients from Parts A and B of the study treated with VX-880 engrafted islet cells, produced endogenous insulin (C-peptide) and had improved glycemic control while reducing or eliminating insulin use. The two patients with at least one year of follow-up met the criteria for the primary endpoint of elimination of severe hypoglycemic events (SHEs) and HbA1C <7.0 and also achieved insulin independence.
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2. VX-264, fully differentiated islet cells encapsulated in immunoprotective device: VX-264 uses the same stem cell-derived, fully differentiated islets used in the VX-880 program, which are encapsulated in a novel device designed to shield the cells from the body’s immune system and obviate the need for immunosuppressive therapy. Vertex is enrolling and dosing patients with VX-264 in a Phase 1/2 clinical trial that is a sequential, multi-part study to evaluate the safety, tolerability and efficacy of VX-264. Part A of the study will dose patients with a partial dose of cells and a stagger between patients, and Part B will dose patients with a full target dose and a stagger between patients before moving to concurrent dosing in Part C. The study is enrolling patients in the U.S., Canada and the Netherlands, with additional global sites to be activated in the coming months. The first patient in Part A has been dosed.

3. Edited fully differentiated cells: Vertex’s hypoimmune cell program involves using CRISPR/Cas9 to gene edit the same stem cell-derived, fully differentiated islets used in the VX-880 and VX-264 programs, in order to cloak the cells from the immune system. This is yet another possible path to eliminate the need for immunosuppressive therapy. This program is progressing through the research stage.

To further expand Vertex’s capabilities in cell therapy manufacturing, in June 2023, Vertex and Lonza announced a strategic agreement to support the manufacture of Vertex’s portfolio of investigational stem cell-derived, fully differentiated insulin-producing islet cell therapy. This agreement will help accelerate the development and commercialization of Vertex’s potentially transformative cell therapy products for T1D.

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.
•Vertex is enrolling and dosing patients in 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. Vertex expects to complete enrollment in this study in 2023.
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•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. Vertex expects to complete enrollment and dosing in this study in 2023.

Muscular Dystrophies
Vertex is also advancing preclinical assets in muscular dystrophies, including Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1).

Investments in External Innovation
As part of the collaboration with CRISPR Therapeutics on hypoimmune cells for T1D, Vertex achieved a research milestone in the second quarter of 2023, resulting in a $70 million milestone payment payable to CRISPR.
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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, (v) an intangible asset impairment charge and (vi) 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 August 1, 2023 Veracyte, Inc. (Nasdaq: VCYT) reported the publication of a large, real-world study reinforcing the Decipher Prostate Genomic Classifier’s ability to guide personalized treatment approaches for men with prostate cancer (Press release, Veracyte, AUG 1, 2023, View Source [SID1234633599]). The study utilized data from the first linkage of prostate cancer cases reported by central cancer registries participating in the Surveillance, Epidemiology, and End Results (SEER) Program, with Decipher test results. SEER is a population-based cancer registry supported by the National Cancer Institute (NCI). The findings appear online in JNCI Cancer Spectrum.

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In the U.S., an estimated 288,300 men are expected to be diagnosed with prostate cancer in 2023 and 34,700 men are expected to die from the disease.[1] Treatment for prostate cancer is primarily selected based on clinical risk factors such as Gleason score, clinical stage and prostate-specific antigen (PSA). Clinical factors alone, however, do not always reflect the true biology of the tumor, which can lead to over- or under-treatment of patients with prostate cancer. The Decipher Prostate test molecularly assesses the likelihood of a patient’s cancer metastasizing within the next five years. Armed with this information, a physician can recommend tailored treatment plans, including no treatment, less intensive treatment or earlier, more intensive interventions.

"Validation from multiple randomized trials has consistently demonstrated the prognostic performance of the Decipher 22-gene expression test," said Daniel Spratt, M.D., chair of the Department of Radiation Oncology at UH Cleveland Medical Center. "This study builds upon this with real-world data of how the test is being used in a population sample and demonstrates how we are moving toward the goal of personalized therapy. Patients with a low Decipher score, indicating a better prognosis, can be guided towards treatment de-escalation, and those with higher Decipher scores, indicating a worse prognosis, can be guided towards appropriate treatment."

The study analyzed data from 8,297 patients in the SEER registry who received a primary prostate cancer diagnosis from 2010 to 2018 and underwent Decipher Prostate testing. Researchers evaluated the association between the patients’ Decipher scores (range 0-1) and risk groups (low, intermediate and high), and the use of active surveillance and watchful waiting (AS/WW) as well as adverse pathology at the time of radical prostatectomy (RP).

The results demonstrated that AS/WW was highest among subjects with low-risk Decipher biopsy results (41%), compared to those who had intermediate-risk (27%) or high-risk (11%) scores. Among subjects with clinically low-risk prostate cancer, 65% of those with low-risk Decipher results were managed with AS/WW. Among patients classified as NCCN low or favorable intermediate risk, higher Decipher risk was associated with greater use of local therapy and nearly three times the odds of harboring adverse pathology compared to those with low Decipher risk. The use of prostatectomy and radiotherapy increased with higher Decipher risk groups. For example, prostatectomy was used in 22% of low-, 30% of intermediate-, and 39% of high-risk Decipher patients and radiotherapy was used in 16% of low-, 24% of intermediate-, and 35% of high-risk Decipher patients. The study also found a significant association between higher Decipher risks groups and the use of post-operative radiotherapy.

"This study is further evidence that the Decipher Prostate test provides valuable clinical information to physicians and their patients with prostate cancer. In contemporary practice, physicians treat patients with higher-risk Decipher scores more aggressively, and patients with lower-risk Decipher scores more conservatively," said Elai Davicioni, Ph.D., Veracyte’s medical director for Urology. "This is the first large national database study in ongoing collaborations with the National Cancer Institute SEER program and represents our sustained commitment to research and real-world evidence development."

On August 1, 2023 Sorrento Therapeutics presented its corporate presentation (Presentation, Sorrento Therapeutics, AUG 1, 2023, View Source [SID1234633598]).

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On August 1, 2023 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported financial results for the second quarter ended June 30, 2023, including sales of TAVALISSE (fostamatinib disodium hexahydrate) tablets for the treatment of adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment and sales of REZLIDHIA (olutasidenib) capsules for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test (Press release, Rigel, AUG 1, 2023, View Source [SID1234633597]).

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"We are encouraged by the progress we made in the second quarter in building our hematology/oncology company," said Raul Rodriguez, Rigel’s president and CEO. "We delivered strong year-over-year revenue growth for TAVALISSE in ITP and hired our dedicated institutional sales team to drive our commercial launch of REZLIDHIA with a focus on awareness and education with healthcare professionals. We also continued to advance our current development programs while evaluating opportunities to expand our hematology/oncology business through internal and external opportunities."

Business Update

In the second quarter of 2023, a total of 2,191 bottles of TAVALISSE were sold in the U.S. During the quarter, 2,265 bottles were shipped directly to patients and clinics, representing the highest number of bottles shipped to patients and clinics in a quarter since launch.
During the second full quarter of launch, a total of 200 bottles of REZLIDHIA were sold in the U.S., representing a 77% increase over Q1 2023. Of those bottles, 187 were shipped directly to patients and clinics.
In June, Rigel presented promising data from an analysis of the Phase 2 clinical trial evaluating REZLIDHIA in 17 patients with mIDH1 AML who were relapsed/refractory to prior venetoclax-based regimens at the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 Hybrid Congress. The data showed clinically meaningful activity with REZLIDHIA, a potent, selective, oral, small-molecule inhibitor of mIDH11, representing an encouraging therapeutic advance in the treatment of this molecularly defined, poor-prognosis patient population.
Rigel also announced the publication in June of an expert review article in Blood Advances examining the development path and positioning of REZLIDHIA in the mIDH1 R/R AML treatment landscape. The authors concluded, "The approval of olutasidenib is a critical addition to the mIDH1 AML treatment landscape with encouragingly durable responses." They recommended treatment with olutasidenib in venetoclax plus HMA failures, based on the available data.
Rigel continues to advance its open-label, Phase 1b clinical trial of R2892, an investigational, potent, and selective IRAK1/4 inhibitor, in patients with lower-risk myeloid dysplastic syndrome (LR-MDS) who are refractory/resistant to prior therapies. Target enrollment in the second cohort of the trial has been completed and Rigel expects to begin enrollment in the third cohort in the near future.
R552, an investigational, potent, and selective RIPK1 inhibitor, is being advanced by Rigel’s partner Eli Lilly. The Phase 2a clinical trial (NCT05848258) studying R552 in adult patients with moderately to severely active rheumatoid arthritis (RA) has been initiated. The trial plans to enroll 100 patients globally.
Financial Update
For the second quarter of 2023, Rigel reported a net loss of $6.6 million, or $0.04 per basic and diluted share, compared to a net loss of $13.5 million, or $0.08 per basic and diluted share, for the same period of 2022.

For the second quarter of 2023, total revenues were $26.9 million, consisting of $21.3 million in TAVALISSE net product sales, $2.6 million in REZLIDHIA net product sales, $2.0 million in contract revenues from collaborations, and $1.0 million in government contract revenue. TAVALISSE net product sales of $21.3 million increased by $2.8 million or 15% compared to $18.6 million in the same period of 2022. Contract revenues from collaborations for the second quarter of 2023 consisted primarily of revenue from Grifols S.A., related to the delivery of drug supplies of $1.2 million and a royalty of $0.8 million. Government contract revenue for the second quarter of 2023 was related to income recognized pursuant to the agreement with the U.S. Department of Defense (DOD) to support Rigel’s ongoing Phase 3 clinical trial of fostamatinib in high-risk hospitalized patients with COVID-19.

For the second quarter of 2023, total costs and expenses were $32.2 million, compared to $42.8 million for the same period of 2022. The decrease in costs and expenses was primarily due to decreased research and development costs due to trial completion activities related to the Phase 3 clinical trial of fostamatinib for wAIHA and the Phase 3 clinical trial of fostamatinib in high-risk hospitalized patients with COVID-19, as well as timing of activities related to Rigel’s IRAK 1/4 inhibitor program.

For the six months ended June 30, 2023, Rigel reported a net loss of $20.1 million, or $0.12 per basic and diluted share, compared to a net loss of $40.9 million, or $0.24 per basic and diluted share, for the same period of 2022.

For the six months ended June 30, 2023, total revenues were $52.9 million, consisting of $43.6 million in TAVALISSE net product sales, $4.0 million in REZLIDHIA net product sales, $4.3 million in contract revenues from collaborations, and $1.0 million in government contract revenue. TAVALISSE net product sales of $43.6 million increased by $8.9 million or 26% compared to $34.7 million in the same period of 2022. Contract revenues from collaborations for the six months ended June 30, 2023, consisted primarily of revenue from Grifols S.A., related to the delivery of drug supplies of $2.8 million and a royalty of $1.5 million. Government contract revenue for the six months ended June 30, 2023, was related to the income recognized pursuant to the previously mentioned agreement with the DOD.

For the six months ended June 30, 2023, total costs and expenses were $70.9 million, compared to $85.8 million for the same period of 2022. The decrease in costs and expenses was primarily due to decreased research and development costs due to trial completion activities related to the Phase 3 clinical trial of fostamatinib for wAIHA and the Phase 3 clinical trial of fostamatinib in high-risk hospitalized patients with COVID-19, as well as timing of activities related to Rigel’s IRAK 1/4 inhibitor program.

As of June 30, 2023, Rigel had cash, cash equivalents and short-term investments of $64.4 million, compared to $58.2 million as of December 31, 2022.

Conference Call and Webcast with Slides Today at 4:30pm Eastern Time
Rigel will hold a live conference call and webcast today at 4:30pm Eastern Time (1:30pm Pacific Time).

Participants can access the live conference call by dialing (877) 407-3088 (domestic) or (201) 389-0927 (international). The conference call will also be webcast live and can be accessed from the Investor Relations section of the company’s website at www.rigel.com. The webcast will be archived and available for replay after the call via the Rigel website.

About ITP
In patients with ITP (immune thrombocytopenia), the immune system attacks and destroys the body’s own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPO-RAs), and splenectomy. However, not all patients respond to existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP.

About AML
Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that in the United States alone, there will be about 20,380 new cases, most in adults, in 2023.3

Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.4 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.5 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need.

About TAVALISSE
Indication
TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Important Safety Information
Warnings and Precautions

Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.
Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to ≥3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.
Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE.
Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation.
TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.
Drug Interactions

Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.
It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.
Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.
Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.
Adverse Reactions

Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).
Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.
Please see www.TAVALISSEUSPI.com for full Prescribing Information.

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

TAVALISSE and TAVLESSE are registered trademarks of Rigel Pharmaceuticals, Inc.

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 in incidence 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 registered trademark of Rigel Pharmaceuticals, Inc.