On February 29, 2024 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported financial results for the fourth quarter and full year ended December 31, 2023, and provided a business update (Press release, Cardiff Oncology, FEB 29, 2024, View Source [SID1234640677]).

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"2024 is a pivotal year for Cardiff Oncology and we are excited for our upcoming randomized data readout from our lead program in first-line mCRC later this year," said Mark Erlander, Ph.D., Chief Executive Officer of Cardiff Oncology. "The mCRC data we shared in August 2023, and the ONSEMBLE data we are disclosing today, demonstrates onvansertib’s contribution to the standard of care of bevacizumab (bev) and chemotherapy in treating RAS-mutated mCRC. Given there have been no new therapies approved in this large cancer indication in the last 20 years, 2024 marks a critical step in realizing onvansertib’s potential to provide clinical benefit to the large number of newly-diagnosed RAS-mutated mCRC patients, and create value for the stakeholders in our company."

Upcoming expected milestones

•First-line RAS-mutated mCRC randomized data readout expected in mid-2024
Company highlights for the quarter ended December 31, 2023, and subsequent weeks include:
•Provided a clinical update on Phase 2 randomized second-line ONSEMBLE trial in mCRC. New clinical data from discontinued second-line randomized ONSEMBLE trial provides further evidence of onvansertib’s improvement of the efficacy for standard of care therapy in bev naïve patients. In the trial, patients who were bev naïve demonstrated an objective response rate (ORR) of 50% on onvansertib. No clinical responses were observed in patients who received standard of care with FOLFIRI/bev or patients who were previously exposed to bev. For additional information, please refer to the press release issued by the Company today which provided an update on the ONSEMBLE trial.
•Announced first patient dosed in its randomized first-line Phase 2 trial, CRDF-004, for patients with RAS-mutated metastatic colorectal cancer. The trial, whose clinical execution is being conducted by Pfizer Ignite, is designed to confirm the dose of onvansertib for a subsequent registrational trial, and generate safety and efficacy data for onvansertib when added to standard of care (SoC) vs. SoC alone. Interim topline results from CRDF-004 are expected in mid-2024. Contingent upon the results, Cardiff Oncology will initiate a Phase 3, randomized trial, CRDF-005, with registrational intent.
•Announced the publication of data from Phase 1b study in second line KRAS-mutated mCRC in Clinical Cancer Research. The findings of the Phase 1b portion of the Phase 1b/2 study for the second-line treatment of patients with KRAS-mutated metastatic colorectal cancer disclosed by Cardiff Oncology

in August 2023 have been published in the peer-reviewed journal Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper).
Full Year 2023 Financial Results:
Liquidity, cash burn, and cash runway
As of December 31, 2023, Cardiff Oncology had approximately $75 million in cash, cash equivalents, and short-term investments.
Net cash used in operating activities for the full year 2023 was approximately $30.9 million, a decrease of approximately $2.9 million from $33.8 million for the same period in 2022.
Based on its current expectations and projections, the Company believes its current cash resources are sufficient to fund its operations into Q3 2025.
Operating results
Total operating expenses were approximately $45.9 million for the full year ended December 31, 2023, an increase of $5.6 million from $40.3 million for the same period in 2022. The increase in operating expenses was primarily due to costs associated with clinical programs and outside service costs related to the development of our lead drug candidate, onvansertib, and higher salaries and staff costs primarily due to increased headcount and stock-based compensation for additional grants to employees.

Conference Call and Webcast

Cardiff Oncology will host a corresponding conference call and live webcast at 4:30 p.m. ET/1:30 p.m. PT on February 29, 2024. Individuals interested in listening to the live conference call may do so by using the webcast link in the "Investors" section of the company’s website at www.cardiffoncology.com. A webcast replay will be available in the investor relations section on the company’s website following the completion of the call.

On February 29, 2024 Amgen (NASDAQ:AMGN) reported that it will present at the 44th Annual TD Cowen Health Care Conference at 9:10 a.m. ET on Tuesday, March 5, 2024 (Press release, Amgen, FEB 29, 2024, View Source [SID1234640676]). Peter Griffith, executive vice president and chief financial officer at Amgen, and Paul Burton, senior vice president and chief medical officer at Amgen, will present at the conference. The webcast will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.

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The webcast, as with other selected presentations regarding developments in Amgen’s business given by management at certain investor and medical conferences, can be found on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

On February 29, 2024 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, radioimmunotherapy and antibody-based therapeutic products for the treatment of cancer, reported financial results for the quarter and full year ended December 31, 2023 (Press release, Y-mAbs Therapeutics, FEB 29, 2024, View Source [SID1234640669]).

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"Y-mAbs has made significant progress across both the development and commercial fronts of our business resulting in a momentous 2023," said Mike Rossi, President and Chief Executive Officer. "From a development standpoint, we demonstrated proof-of-concept of our Self-Assembly DisAssembly ("SADA") Pretargeted Radioimmunotherapy ("PRIT") platform, showing that GD2-SADA targets and binds to tumors in humans in a Phase 1 trial. We continue to expect to present mature data from Part A of our Phase 1 GD2-SADA clinical trial at a medical meeting in the second half of this year. In addition, we look forward to initiating our CD38-SADA Phase 1 trial this year. While we continue to advance our SADA PRIT platform and programs through clinical development, we are supported by the solid commercial performance of DANYELZA (naxitamab-gqgk). We achieved record quarterly and annual net product revenues, and sales continue trending upward as more high-volume centers deploy DANYELZA for their patients. Our strong financial foundation and operational performance continue to fuel our mission of providing better and safe therapies for a variety of cancers and improve the lives of patients and their families."

Fourth Quarter 2023 and Recent Corporate Developments

· In December 2023, Y-mAbs announced that it was added to the NASDAQ Biotechnology Index (NASDAQ: NBI), effective December 18, 2023.
· On October 18, 2023, Y-mAbs announced that its Board of Directors appointed radiopharmaceutical industry veteran Mr. Rossi as President and Chief Executive Officer, effective November 6, 2023. Thomas Gad, who founded Y-mAbs in 2015 and has served as Interim Chief Executive Officer since 2022, transitioned to the role of Vice Chairman of the Board of Directors and Chief Business Officer.
· On October 17, 2023, the U.S. FDA cleared Y-mAbs’ IND for CD38-SADA, marking the second clinical development program utilizing the Company’s novel SADA PRIT technology platform.
· On October 16, 2023, Y-mAbs announced the publication of a study of naxitamab-based chemoimmunotherapy ("HITS") study in patients with refractory high-risk neuroblastoma ("HR-NB") in the journal Cancers. The study investigated the HITS combination in patients with HR-NB who did not respond well to induction or refractory therapy. Patients who received HITS immediately after induction had higher response rates (47% vs. 18%) and superior estimated three-year overall survival (85% vs. 29%), compared with those who received the same combination regimen later in the course of treatment. The publication is entitled, "Early Salvage Chemo-Immunotherapy with Irinotecan, Temozolomide and Naxitamab Plus GM-CSF (HITS) for Patients with Primary Refractory High-Risk Neuroblastoma Provide the Best Chance for Long-Term Outcomes."

On October 11, 2023, Y-mAbs showcased three poster presentations, in addition to an online publication, of DANYELZA at the 55th Congress of the International Society of Pediatric Oncology in Ottawa, Canada.

Financial Results

Revenues

DANYELZA net product revenues were $23.4 million and $84.3 million for the quarter and year ended December 31, 2023, which represented increases of 42% and 71%, respectively, over $16.4 million and $49.3 million in the comparable periods of 2022. The DANYELZA net product revenues of $23.4 million in the fourth quarter of 2023, represented a favorable 17% increase compared to the third quarter of 2023, primarily driven by increased U.S. sales.

As of December 31, 2023, Y-mAbs has delivered DANYELZA to 58 centers across the U.S. since initial launch, with ten new accounts added in 2023.

The Company did not have license revenues in the quarter ended December 31, 2023 and had license revenues of $0.5 million for the year ended December 31, 2023. The Company reported license revenues of $15.0 million and $16.0 million for the quarter and year ended December 31, 2022. License revenues for the year ended December 31, 2023 arose from the September 2023 achievement of marketing authorization for DANYELZA in Mexico under the Company’s sublicense agreement with Adium. During the quarter and year ended December 31, 2022, the Company recognized a regulatory-based milestone of $15.0 million from SciClone Pharmaceuticals International Ltd. for the conditional approval of DANYELZA in China.

Operating Costs and Expenses

Cost of Goods Sold

Cost of goods sold was $2.0 million for the quarters ended December 31, 2023 and 2022, respectively. The cost of goods sold was $11.4 million and $7.5 million for the years ended December 31, 2023, and 2022, respectively. The increase in cost of goods sold in both periods was primarily driven by increased product revenues. The Company experienced inventory write-downs of $0.8 million and $1.2 million in the years ended December 31, 2023, and December 31, 2022, respectively.

The Company’s gross margin, excluding the 2023 and 2022 inventory write-downs, increased in the fourth quarter of 2023 to 91% due to the gross margin increase from higher U.S. revenues. The Company’s gross margin, excluding the 2023 and 2022 inventory write-downs, remained constant at 87% for the year ended December 31, 2023, compared to the year ended December 31, 2022, which was the net impact of the gross margin increase from higher U.S. revenues, offset by increased revenues from geographic areas outside the U.S., which were at a lower gross margin. The Company defines gross margin as net product revenues less cost of goods sold divided by net product revenues.

Research and Development

Research and development expenses were $13.4 million for the quarter ended December 31, 2023, a reduction of 32% compared to $19.8 million for the quarter ended December 31, 2022. The $6.4 million decrease was primarily due to decreased spending on deprioritized programs, which resulted in a $3.1 million decrease in outsourced manufacturing, a $2.0 million decrease in personnel-related costs, inclusive of stock-based compensation, and a $2.2 million decrease in outsourced research and supplies, partially offset by a $1.2 million increase in clinical trials expenses.

For the year ended December 31, 2023, research and development expenses were $54.2 million, a reduction of 41% compared to $91.6 million for the year ended December 31, 2022. The $37.4 million decrease was primarily due to decreased spending on deprioritized programs, resulting in a $21.0 million decrease in outsourced manufacturing, a $9.0 million decrease in outsourced research and supplies, a $6.1 million decrease in personnel-related costs, inclusive of stock-based compensation, and a $2.0 million decrease in clinical trials, partially offset by a $3.8 million increase in milestones and license acquisition costs primarily related to a $4.1 million increase in milestones accrued under the Company’s SADA License Agreement, as the Company determined that achievement of certain time-based clinical milestones within the agreement are probable based on the availability of data and the assessment of clinical progress in the year of 2023.

The $2.0 million and $6.1 million decreases in personnel-related costs during the quarter and year ended December 31, 2023, respectively, were driven by the headcount reduction as part of the Company’s restructuring plan announced in January 2023. The expense reduction in the year ended December 31, 2023 was partially offset by severance charges recognized in conjunction with the restructuring plan.

Selling, General, and Administration

Selling, general, and administrative expenses were $11.1 million for the quarter ended December 31, 2023, which was a slight increase compared to $10.8 million for the quarter ended December 31, 2022.

For the year ended December 31, 2023, selling, general, and administrative expenses were $44.9 million, a reduction of 26% compared to $60.9 million for the year ended December 31, 2022. The $16.0 million decrease in selling, general and administrative expenses was primarily attributable to a $10.9 million charge in the year ended December 31, 2022 related to contractual severance-related benefits for the Company’s former Chief Executive Officer, and, to a lesser extent, a $3.4 million decrease in commercialization expenses, inclusive of costs of incurred in 2022 in anticipation of a potential omburtamab launch.

Interest and Other Income/(Loss)

Interest and other income/(loss) was relatively unchanged at $2.4 million as compared to $2.3 million during the quarters ended December 31, 2023 and 2022, respectively. Interest and other income/(loss) was $4.8 million of income as compared to $0.8 million of loss for the years ended December 31, 2023 and 2022, respectively. The $5.6 million favorable change in interest and other income/(loss), reflects increased interest income for the year ended December 31, 2023, and was driven by increased money market fund investment income. The Company recorded impairment charges totaling $1.4 million related to the write down of two Secured Promissory Notes during the year ended December 31, 2022.

Net Loss

Y-mAbs reported a net loss for the quarter ended December 31, 2023, of $1.0 million, or ($0.02) per basic and diluted share, compared to net income of $1.2 million, or $0.03 per basic and diluted share, for the quarter ended December 31, 2022. The net income for the quarter ended December 31, 2022, was after $15.0 million of license revenue recognized in the fourth quarter of 2022. For the year ended December 31, 2023, the Company reported a net loss of $21.4 million, or ($0.49) per basic and diluted share, compared to a net loss of $95.6 million, or ($2.19) per basic and diluted share, for the year ended December 31, 2022. The favorable decrease in net loss for the year ended December 31, 2023, was primarily driven by an increase in U.S. and international DANYELZA product revenues for the year ended December 31, 2023, as well as decreased research and development cost, and decreased selling, general and administration cost.

Cash and Cash Equivalents

As of December 31, 2023, Y-mAbs had approximately $78.6 million in cash and cash equivalents which, together with anticipated DANYELZA product revenues, is expected to support operations as currently planned into 2027. This estimate reflects the Company’s current business plan that is supported by assumptions that may prove to be inaccurate, such that Y-mAbs could use its available capital resources sooner than it currently expects.

2024 Financial Guidance

· Anticipated DANYELZA net product revenues of between $95 million and $100 million;
· Anticipated operating expenses of between $115 million and $120 million;
· Anticipated total annual cash burn of between $15 million and $20 million; and
· Cash and cash equivalents anticipated to continue to support operations as currently planned into 2027.

Webcast and Conference Call

Y-mAbs will host a conference call on Friday, March 1, 2024, at 8:00 a.m. ET. To participate in the call, please use the following dial-in information.

Investors (domestic): (877) 407-0792
Investors (international): (201) 689-8263
Conference ID: 13744085

To access a live webcast of the update, please use this link. Prior to the call and webcast, a slide presentation pertaining to our quarterly earnings will be made available in the investor relations section of our website, www.ymabs.com, shortly before the call begins.

On February 29, 2024 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a clinical-stage precision oncology company focused on the treatment and prevention of virus-associated cancers that impact patients worldwide, reported that its lead development program, Nana-val (nanatinostat in combination with valganciclovir), a first-in-class, all-oral investigational therapy targeting Epstein-Barr virus (EBV)-associated cancers, has completed Stage 2 enrollment into the relapsed or refractory (R/R) Epstein-Barr virus-positive (EBV+) peripheral T-cell lymphoma (PTCL) cohort of the NAVAL-1 trial (Press release, Viracta Therapeutics, FEB 29, 2024, View Source [SID1234640668]).

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"Given the nature of this serious life-threatening condition and absence of EBV-targeted treatments today, our goal is to bring Nana-val to patients with relapsed or refractory EBV-positive PTCL as quickly as possible," said Darrel P. Cohen, M.D., Ph.D., Chief Medical Officer of Viracta. "The completion of Stage 2 enrollment of the PTCL cohort in NAVAL-1 is a major milestone for the Nana-val clinical development program. We would like to acknowledge the dedication of our study execution team and the commitment of our investigators for this achievement. We look forward to building upon our previously published positive data from the Phase 1b/2 clinical trial and reporting topline PTCL cohort data from Stage 1 of the NAVAL-1 trial in the second quarter of 2024. Additionally, we plan to meet with FDA in mid-2024 to align on requirements for accelerated approval of Nana-val in this orphan indication."

Upcoming Anticipated Milestones for the NAVAL-1 Trial of Nana-val in Patients with R/R EBV+ PTCL

Present topline Stage 1 data from both arms (in patients treated with nanatinostat with [n=10] or without [n=10] valganciclovir) in the second quarter of 2024, with an aim to clearly delineate the differentiation of Nana-val’s ‘kick and kill’ mechanism of action.
Present Stage 1 + Stage 2 data (n=21) from the R/R EBV+ PTCL cohort in patients treated with Nana-val in the third quarter of 2024.
Engage with the U.S. Food and Drug Administration (FDA) in mid-2024, to align on requirements for accelerated approval.
Enroll patients into the post-Phase 2 expansion cohort to support potential accelerated approval.
About the NAVAL-1 Trial
NAVAL-1 (NCT05011058) is a global, multicenter, clinical trial of Nana-val in patients with relapsed or refractory (R/R) Epstein-Barr virus-positive (EBV+) lymphoma. This trial employs a Simon two-stage design where, in Stage 1, participants are enrolled into one of three indication cohorts based on EBV+ lymphoma subtype. If two objective responses are achieved within a lymphoma subtype in Stage 1 (n=10), then additional patients will be enrolled in Stage 2 for a total of 21 patients. EBV+ lymphoma subtypes demonstrating promising antitumor activity in Stage 2 may be further expanded following discussion with regulators to potentially support registration.

About Nana-val (Nanatinostat and Valganciclovir)
Nanatinostat is an orally available histone deacetylase (HDAC) inhibitor being developed by Viracta. Nanatinostat is selective for specific isoforms of Class I HDACs, which are key to inducing viral genes that are epigenetically silenced in Epstein-Barr virus (EBV)-associated malignancies. Nanatinostat is currently being investigated in combination with the antiviral agent valganciclovir as an all-oral combination therapy, Nana-val, in various subtypes of EBV-associated malignancies. Ongoing trials include a pivotal, global, multicenter, open-label Phase 2 basket trial in multiple subtypes of relapsed or refractory (R/R) EBV+ lymphoma (NAVAL-1) as well as a multinational Phase 1b/2 clinical trial in patients with recurrent or metastatic (R/M) EBV+ NPC and other advanced EBV+ solid tumors.

About Peripheral T-Cell Lymphoma
T-cell lymphomas comprise a heterogeneous group of rare and aggressive malignancies, including peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL). There are approximately 5,600 newly diagnosed T-cell lymphoma patients and approximately 2,600 newly diagnosed PTCL-NOS and AITL patients in the U.S. annually. Approximately 70% of these patients are either refractory to first-line therapy, or eventually experience relapse of their disease. Clinical trials are currently recommended for all lines of PTCL therapy, and most patients with R/R PTCL have poor outcomes, with median progression-free survival and median overall survival times reported to be 3.7 and 6.5 months, respectively. Approximately 40% to 65% of PTCL is associated with EBV, the incidence of EBV+ PTCL varies by geography, and reported outcomes for patients with EBV+ PTCL are inferior to those whose disease is EBV-negative. There is no approved targeted treatment specific for EBV+ PTCL, and therefore this represents a high unmet medical need.

About EBV-Associated Cancers
Approximately 90% of the world’s adult population is infected with EBV. Infections are commonly asymptomatic or associated with mononucleosis. Following infection, the virus remains latent in a small subset of cells for the duration of the patient’s life. Cells containing latent virus are increasingly susceptible to malignant transformation. Patients who are immunocompromised are at an increased risk of developing EBV-positive (EBV+) lymphomas. EBV is estimated to be associated with approximately 2% of the global cancer burden including lymphoma, nasopharyngeal carcinoma (NPC), and gastric cancer.

On February 29, 2024 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, reported that the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for nirogacestat, an oral gamma secretase inhibitor, for the treatment of adults with desmoid tumors (Press release, SpringWorks Therapeutics, FEB 29, 2024, View Source [SID1234640667]). If approved, nirogacestat will be the first therapy to receive marketing authorization in the European Union (EU) for the treatment of desmoid tumors. Nirogacestat previously received Orphan Drug designation from the European Commission for the treatment of soft tissue sarcoma.

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"The validation of our marketing authorization application is an important step towards bringing nirogacestat to patients with desmoid tumors in the European Union who currently do not have an approved therapy," said Saqib Islam, Chief Executive Officer of SpringWorks. "We look forward to working with the EMA on this important submission."

The MAA submission is based on results from the Phase 3 DeFi trial. In DeFi, nirogacestat met the primary endpoint of improving progression-free survival (PFS), demonstrating a statistically significant improvement over placebo with a 71% reduction in the risk of disease progression (hazard ratio (HR) = 0.29 (95% CI: 0.15, 0.55); p< 0.001). Median PFS was not reached in the nirogacestat arm and was 15.1 months in the placebo arm. Confirmed objective response rate (ORR) based on blinded independent central review of Response Evaluation Criteria in Solid Tumors v1.1 was 41% with nirogacestat versus 8% with placebo (p<0.001); the complete response rate was 7% in the nirogacestat arm and 0% in the placebo arm. Nirogacestat also demonstrated early and sustained improvements in patient-reported outcomes (PROs) measured as of the cycle 10 assessment, including pain (p<0.001), desmoid tumor-specific symptoms (p<0.001), physical/role functioning (p<0.001), and overall health-related quality of life (p≤0.01). Nirogacestat exhibited a manageable safety and tolerability profile. The most common adverse events (>15%) reported in patients receiving nirogacestat were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea. The DeFi trial results were published in the March 9, 2023 edition of the New England Journal of Medicine and presented during a Presidential Symposium at the European Society for Medical Oncology Congress 2022.1, 2

"Desmoid tumors can have a significant impact on patients’ lives and there is a pressing need for a new treatment for patients in Europe," said Bernd Kasper, M.D., Ph.D., University of Heidelberg, Mannheim Cancer Center, Mannheim, Germany and Principal Investigator of the DeFi trial. "In the DeFi trial, nirogacestat demonstrated significant improvements across progression-free survival, objective response rate, and patient-reported outcomes, and had a safety profile that supports long-term dosing. These results support that nirogacestat will be a practice-changing therapy if approved by the EMA."

In November 2023, the U.S. Food and Drug Administration approved OGSIVEO (nirogacestat) for the treatment of adults with progressing desmoid tumors who require systemic treatment. The U.S. prescribing information includes the following Warnings & Precautions: diarrhea, ovarian toxicity, hepatotoxicity, non-melanoma skin cancers, electrolyte abnormalities, and embryo-fetal toxicity. Please see below for additional Important Safety Information.

About Desmoid Tumors

Desmoid tumors (sometimes referred to as aggressive fibromatosis, or desmoid fibromatosis) are rare, aggressive, locally invasive tumors of the soft tissues that can be serious, debilitating, and, in rare cases when vital structures are impacted, life-threatening.3,4

Desmoid tumors are most commonly diagnosed in patients between the ages of 20 and 44 years, with a two-to-three times higher prevalence in females. 5,6 In the European Union, the incidence of desmoid tumors is estimated to be approximately 3-5 cases per million per year.7

Although they do not metastasize, desmoid tumors are associated with recurrence rates of up to 77% after surgical resection.5,8,9 Desmoid tumor experts and treatment guidelines now recommend systemic therapies as first-line intervention instead of surgery for most tumor locations requiring treatment.9

About OGSIVEO (nirogacestat)

OGSIVEO (nirogacestat) is an oral, selective, small molecule gamma secretase inhibitor approved in the United States for the treatment of adult patients with progressing desmoid tumors who require systemic treatment.

OGSIVEO is not approved for the treatment of any other indication in the United States, or for any indication in any other jurisdiction by any other health authority.

SpringWorks is also evaluating nirogacestat as a potential treatment for patients with ovarian granulosa cell tumors and for patients with multiple myeloma as part of several B-cell maturation agent (BCMA) combination therapy regimens in collaboration with leaders in industry and academia.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Diarrhea: Diarrhea occurred in 84% of patients treated with OGSIVEO. Grade 3 events occurred in 16% of patients. Monitor patients and manage using antidiarrheal medications. Modify dose as recommended.
Ovarian Toxicity: Female reproductive function and fertility may be impaired in patients treated with OGSIVEO. Impact on fertility may depend on factors like duration of therapy and state of gonadal function at time of treatment. Long-term effects on fertility have not been established. Advise patients on the potential risks for ovarian toxicity before initiating treatment. Monitor patients for changes in menstrual cycle regularity or the development of symptoms of estrogen deficiency, including hot flashes, night sweats, and vaginal dryness.
Hepatotoxicity: ALT or AST elevations occurred in 30% and 33% of patients, respectively. Grade 3 ALT or AST elevations (>5 × ULN) occurred in 6% and 2.9% of patients. Monitor liver function tests regularly and modify dose as recommended.
Non-Melanoma Skin Cancers: New cutaneous squamous cell carcinoma and basal cell carcinoma occurred in 2.9% and 1.4% of patients, respectively. Perform dermatologic evaluations prior to initiation of OGSIVEO and routinely during treatment.
Electrolyte Abnormalities: Decreased phosphate (65%) and potassium (22%) occurred in OGSIVEO-treated patients. Phosphate <2 mg/dL occurred in 20% of patients. Grade 3 decreased potassium occurred in 1.4% of patients. Monitor phosphate and potassium levels regularly and supplement as necessary. Modify dose as recommended.
Embryo-Fetal Toxicity: Oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity at maternal exposures below human exposure at the recommended dose of 150 mg twice daily. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during treatment with OGSIVEO and for 1 week after the last dose.
ADVERSE REACTIONS

The most common (≥15%) adverse reactions were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea.
Serious adverse reactions occurring in ≥2% of patients were ovarian toxicity (4%).
The most common laboratory abnormalities (≥15%) were decreased phosphate, increased urine glucose, increased urine protein, increased AST, increased ALT, and decreased potassium.
DRUG INTERACTIONS

CYP3A Inhibitors and Inducers: Avoid concomitant use with strong or moderate CYP3A inhibitors (including grapefruit products, Seville oranges, and starfruit) and strong or moderate CYP3A inducers.
Gastric Acid Reducing Agents: Avoid concomitant use with proton pump inhibitors and H2 blockers. If concomitant use cannot be avoided, OGSIVEO can be staggered with antacids (e.g., administer OGSIVEO 2 hours before or 2 hours after antacid use).
Consult the full Prescribing Information prior to and during treatment for important drug interactions.
To report suspected adverse reactions, contact SpringWorks Therapeutics at 1-888-400-SWTX (1-888-400-7989) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full U.S. Prescribing Information for OGSIVEO for more information.