On November 7, 2024 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, reported that long-term efficacy and safety data from the Phase 3 DeFi trial of nirogacestat in adults with progressing desmoid tumors will be presented as a late-breaking oral presentation at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting, being held November 13-16, 2024, in San Diego, CA (Press release, SpringWorks Therapeutics, NOV 7, 2024, View Source [SID1234647949]). These results, utilizing an August 2024 data cutoff date, showed that longer-term treatment with nirogacestat was associated with further reductions in tumor size, increase in objective response rate (ORR) with additional partial responses (PRs) and complete responses (CRs), sustained improvements in desmoid tumor symptoms including pain, and a consistent safety profile compared to the April 2022 data cut utilized for the primary results of the trial.

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"Our findings demonstrate that longer-term nirogacestat treatment was associated with durable tumor size reductions, evidence of deepening responses, and sustained benefits in pain, physical functioning and other desmoid tumor symptoms," said Ravin Ratan, M.D., M.Ed., Associate Professor, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in Houston, and DeFi study investigator presenting the data at CTOS. "Given the oftentimes persistent and debilitating nature of desmoid tumors, these results are meaningful for patients and clinicians as they provide valuable insights on the longer-term use of this medicine."

"We are pleased that the growing body of evidence from the DeFi trial continues to support the significant benefits that OGSIVEO is providing for patients with desmoid tumors," said Jim Cassidy, M.D., Ph.D., Chief Medical Officer of SpringWorks Therapeutics. "It is also gratifying that feedback from the real-world setting is consistent with our clinical trial experience, with patients reporting rapid, sustained and continued symptomatic relief, which is contributing to their overall improved quality of life."

Additional DeFi data to be presented at CTOS include an oral presentation of a post-hoc analysis assessing the effect of nirogacestat in subgroups of patients with desmoid tumors who have risk factors associated with poor prognosis and a poster on patients with CTNNB1 and APC mutations.

Oral Presentations at the CTOS 2024 Annual Meeting

Nirogacestat treatment in adult patients with desmoid tumors: Long-term efficacy and safety from the Phase 3 DeFi trial
Date and Time: November 16, 3:30-4:30 p.m. PT (6:30-7:30 p.m. ET)

As previously reported, 70 patients were randomized to nirogacestat in the double-blind (DB) portion of the Phase 3 DeFi trial (NCT03785964); these patients achieved statistically and clinically significant improvement in progression-free survival (PFS) and ORR, as well as rapid and sustained improvement in pain, physical functioning, role functioning and overall quality of life, as compared to those randomized to placebo. At the primary analysis data cut-off date (April 2022), the median (range) duration of nirogacestat treatment was 20.6 (0.3-33.6) months. Following the DB portion of the study, patients could continue to receive nirogacestat as part of the open-label extension (OLE). As of this long-term follow-up analysis (August 2024 data cut-off date), the median (range) duration of nirogacestat treatment in these patients was 33.6 (0.3 to 60) months. The data being presented at CTOS evaluated the overall efficacy and safety of continuous nirogacestat treatment in patients initially randomized to nirogacestat in DeFi and further explored safety and efficacy analyses at milestones of one, two, three, and four years on treatment.

Results demonstrated that:

Three new PRs and three new CRs were reported using the August 2024 versus the April 2022 data cut-off date, resulting in an ORR of 45.7% (34.3% PR, 11.4% CR) (N=70).
The median best percent reduction from baseline in target tumor size by RECIST 1.1 with continuous nirogacestat treatment was −32.3% at year one (n=46) and −75.8% for patients completing at least four years (n=15) of treatment.
Improvement in patient reported outcomes (PROs) of pain, desmoid tumor-specific symptom severity, and desmoid tumor-specific physical functioning, which occurred early (at Cycle 2, the first post-treatment timepoint evaluated as disclosed at the primary analysis) and were sustained with up to 45 months of treatment with nirogacestat.
The most frequently reported treatment emergent adverse events (TEAEs) that occurred in >20% of patients receiving nirogacestat over the entire treatment period were diarrhea, nausea, fatigue, hypophosphatemia, and headache, and were generally consistent between the April 2022 and August 2024 data cutoffs. Most events were Grade 1 or 2, with first onset occurring in the first year of treatment for most patients. Overall, the incidence and severity of frequently reported TEAEs decreased through years two, three and four of treatment.
Efficacy of nirogacestat in patients with poor prognostic factors for desmoid tumors: patient-reported outcomes, progression-free survival, and objective response in the phase 3 DeFi trial
Date and Time: November 16, 3:30-4:30 p.m. PT (6:30-7:30 p.m. ET)

A post hoc analysis of the DeFi trial was conducted to assess the effect of nirogacestat on PFS, ORR and PROs in subgroups of patients with desmoid tumors who have risk factors associated with a poor prognosis: larger tumor size (>10 cm), younger age (≤30 years), specific types of CTNNB1 gene mutations, and presence of pain at baseline. Results include:

Treatment with nirogacestat led to consistent improvements in PFS, ORR and PROs versus placebo regardless of the patient subgroups.
The ORR risk difference between nirogacestat and placebo ranged from 18.1% to 56.0%, favoring nirogacestat.
Compared with placebo, patients treated with nirogacestat generally reported greater improvement from baseline at cycle 10 in PROs (pain, desmoid tumor-specific symptom burden, physical and role functioning, and overall quality of life) across subgroups of patient-related and tumor-related poor prognostic factors.
The authors concluded that nirogacestat demonstrates uniform efficacy and consistent improvement in PROs across the desmoid tumor population.
Poster Presentations at the CTOS 2024 Annual Meeting

Descriptive evaluation of patients with desmoid tumor and co-occurring somatic mutations of CTNNB1 and APC in the Phase 3 DeFi trial
Date and Time: November 14, 5:45-6:45 p.m. PT (8:45-9:45 p.m. ET)

This analysis identified three patients with desmoid tumors enrolled in the DeFi trial who had co-occurring somatic mutations of CTNNB1 and APC, including two treated with nirogacestat. Both patients achieved a best overall response of partial response (with time to response of 6.0 and 13.8 months). Although the small number of patients limited a formal analysis, descriptive results suggest that patients with this mutational profile benefit from nirogacestat treatment in a manner that is generally consistent with the overall DeFi study population but may take longer to experience a treatment response.

About the DeFi Trial

DeFi (NCT03785964) is a global, randomized (1:1), multicenter, double-blind, placebo-controlled pivotal Phase 3 trial evaluating the efficacy, safety and tolerability of nirogacestat in adult patients with progressing desmoid tumors. The double-blind phase of the study randomized 142 patients (nirogacestat, n=70; placebo n=72) to receive 150 mg of nirogacestat or placebo twice daily. Key eligibility criteria included tumor progression by ≥20% as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) within 12 months prior to screening. The primary endpoint was progression-free survival (PFS), as assessed by blinded independent central review, or death by any cause. Secondary and exploratory endpoints include safety and tolerability measures, objective response rate (ORR), duration of response, changes in tumor volume assessed by magnetic resonance imaging (MRI), and changes in patient-reported outcomes (PROs). DeFi includes an open-label extension phase, which is ongoing.

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.1,2

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.3,4 It is estimated that there are 1,000-1,650 new cases diagnosed per year in the United States.4,5,6

Although they do not metastasize, desmoid tumors are associated with recurrence rates of up to 77% after surgical resection.3,7.8 Desmoid tumor experts and treatment guidelines now recommend systemic therapies as first-line intervention instead of surgery for most tumor locations requiring treatment.8

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, sometimes severe, can occur in patients treated with OGSIVEO. Diarrhea occurred in 84% of patients treated with OGSIVEO, and included Grade 3 events in 16% of patients. Median time to first diarrhea event was 9 days (range: 2 to 434 days). 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 of OGSIVEO 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: OGSIVEO can cause fetal harm when administered to pregnant women. Oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity and death 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 (84%), ovarian toxicity (75% in the 36 females of reproductive potential), rash (68%), nausea (54%), fatigue (54%), stomatitis (39%), headache (30%), abdominal pain (22%), cough (20%), alopecia (19%), upper respiratory tract infection (17%), and dyspnea (16%).
Serious adverse reactions occurred in 20% of patients who received OGSIVEO. 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.
USE IN SPECIFIC POPULATIONS

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with OGSIVEO and for 1 week after the last dose.
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.

On November 7, 2024 Carisma Therapeutics Inc. (Nasdaq: CARM) ("Carisma" or the "Company"), a clinical-stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported financial results for the quarter ended September 30, 2024, and highlighted recent business updates (Press release, Carisma Therapeutics, NOV 7, 2024, View Source [SID1234647948]).

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"Our recent progress across clinical and preclinical programs demonstrates our commitment to pioneering therapies that address significant unmet medical needs," said Steven Kelly, President and CEO of Carisma Therapeutics. "We are advancing on multiple fronts. We expect to report initial data from the Phase 1 study of CT-0525 in the first quarter of 2025. We also recently nominated our first development candidate in hepatocellular carcinoma with Moderna and are excited to bring additional in vivo CAR-M therapies forward, including autoimmune targets. Our liver fibrosis program is progressing as well, with the nomination of a development candidate anticipated in the first quarter of 2025. These key milestones move us closer to delivering transformative treatments for patients in need."

Third Quarter 2024 Highlights and Upcoming Milestones

Ex Vivo Oncology

· CT-0525 (Anti-HER2 chimeric antigen receptor monocyte (CAR-Monocyte))

o On November 5, 2024, Carisma announced the upcoming presentation of a trial in progress (TIP) poster for its Phase 1 clinical trial evaluating CT-0525, an autologous CAR-Monocyte therapy for the treatment of HER2+ solid tumors. The poster will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Houston, Texas, on November 8, 2024.

o In September 2024, Carisma submitted a protocol amendment for its Phase 1 study of CT-0525 to allow for the expansion of the study to include repeat dosing (up to two billion CAR positive cells administered every three weeks for up to five cycles) in combination with pembrolizumab, bolus dosing (up to10 billion CAR positive cells in a single dose) in combination with pembrolizumab, or either of these two dosing schedules as monotherapy (without checkpoint inhibitor). Repeat dosing in combination with pembrolizumab will be prioritized and the other three study arms may be activated as data indicates.

o Carisma expects to report initial data for Cohorts 1 and 2 of its Phase 1 study of CT-0525 in the first quarter of 2025.

In Vivo Program (Moderna Collaboration)

· Autoimmune disease (CAR-M + mRNA/LNP)

o On September 10, 2024, Carisma announced the expansion of its in vivo chimeric antigen receptor macrophage and monocyte ("CAR-M") collaboration with Moderna, Inc. ("Moderna") to include the nomination of two research targets for the treatment of autoimmune diseases. Carisma retains all rights in autoimmune disease beyond the two nominated targets, which will be exclusively partnered with Moderna.

· GPC3+ solid tumors (CAR-M + mRNA/LNP)

o On November 5, 2024, Carisma announced the upcoming presentation of new pre-clinical data for its anti-GPC3 in vivo CAR-M therapy for the treatment of hepatocellular carcinoma (HCC), developed in collaboration with Moderna. These data will be presented in a poster session at the SITC (Free SITC Whitepaper) Annual Meeting in Houston, Texas, on November 8, 2024. These preclinical data demonstrate robust anti-tumor activity and introduce a novel, off-the-shelf approach for GPC3+ solid tumors.

Fibrosis

o On August 6, 2024, Carisma announced that new preclinical data for liver fibrosis will be highlighted in a poster presentation at the American Association for the Study of Liver Diseases (AASLD) – The Liver Meeting 2024, to be held November 15 through 19, 2024, in San Diego, California.

o Carisma expects to nominate a development candidate for its liver fibrosis program in the first quarter of 2025.

Corporate Update

· On October 30, 2024, Carisma announced the appointment of Sohanya Cheng to the Board of Directors of the Company, effective October 31, 2024. Ms. Cheng brings over 20 years of experience in biopharmaceutical commercialization and research, with a strong focus on oncology. The Company concurrently announced the resignation of Michael Torok from Carisma’s Board of Directors, also effective October 31, 2024.

Third Quarter 2024 Financial Results

· Cash and cash equivalents as of September 30, 2024, were $26.9 million, compared to $40.4 million as of June 30, 2024.

· Research and development expenses for the three months ended September 30, 2024 were $11.3 million, compared to $19.6 million for the three months ended September 30, 2023. The decrease of $8.3 million was primarily due to implementation of our revised operating plan in the second quarter of 2024 in which we halted further development of CT-0508, paused development of CT-1119 and implemented a workforce reduction. As result of the revised operating plan, we experienced a decrease of $2.4 million related to halting development of CT-0508 and a $0.1 million decrease from pausing the development of CT-1119. In addition, the implementation of the revised operating plan resulted in a decrease in facilities and other expenses of $3.1 million due to less laboratory supplies and laboratory space needs and a $0.9 million decrease in direct personnel costs due to a reduction in headcount. Further, we experienced a $0.9 million decrease in direct costs associated with pre-clinical development of CT-0525 due to the timing of the development program and a decrease of $0.9 million in other clinical and pre-clinical development expenses resulting from the timing of certain studies in our in vivo collaboration with Moderna.

· General and administrative expenses for the three months ended September 30, 2024 were $5.2 million, compared to $6.6 million for the three months ended September 30, 2023. The decrease of $1.4 million was primarily due to our revised operating plan in which we recognized a $1.3 million decrease in professional fees as a result of our patent portfolio and expanding infrastructure in 2023, a $0.3 million decrease in facilities and supplies due to a decrease in office expenditures, a $0.2 million decrease in insurance costs, and a $0.1 million decrease in other expenses related to a decline in travel costs, partially offset by a $0.5 million increase in personnel costs driven by an increase in stock-based compensation.

· Net loss was $12.7 million for the third quarter of 2024, compared to a $21.4 million net loss for the same period in 2023.

Outlook

Carisma anticipates that its cash and cash equivalents of $26.9 million as of September 30, 2024 are sufficient to sustain its planned operations into the third quarter of 2025. The Company’s cash forecast contains estimates and assumptions, and management cannot predict the timing of all cash receipts and expenditures with certainty. Variances from management’s estimates and assumptions could impact the Company’s liquidity prior to the third quarter of 2025.

About CT-0525

CT-0525 is a first-in-class, ex vivo gene-modified autologous chimeric antigen receptor-monocyte (CAR-Monocyte) cellular therapy intended to treat solid tumors that overexpress human epidermal growth factor receptor 2 (HER2). It is being studied in a multi-center, open label, Phase 1 clinical trial for patients with advanced/metastatic HER2-overexpressing solid tumors that have progressed on available therapies. The CAR-Monocyte approach has the potential to address some of the challenges of treating solid tumors with cell therapies, including tumor infiltration, immunosuppression within the tumor microenvironment, and antigen heterogeneity. CT-0525 has the potential to enable significant dose escalation, enhance tumor infiltration, increase persistence, and reduce manufacturing time compared to macrophage therapy.

On November 7, 2024 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), a commercial stage biotechnology company focused on hematologic disorders and cancer, reported financial results for the third quarter ended September 30, 2024, including sales of TAVALISSE (fostamatinib disodium hexahydrate) for the treatment of chronic immune thrombocytopenia (ITP); REZLIDHIA (olutasidenib) for the treatment of relapsed or refractory (R/R) mutated isocitrate dehydrogenase-1 (mIDH1) acute myeloid leukemia (AML); and GAVRETO (pralsetinib) for the treatment of metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) and advanced or metastatic thyroid cancer, and recent business progress (Press release, Rigel, NOV 7, 2024, View Source [SID1234647947]).

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"2024 has been a significant year for Rigel, marked by the acquisition of GAVRETO, our third commercial product, strong revenue growth across our commercial portfolio, and the advancement of our development pipeline," said Raul Rodriguez, Rigel’s president and CEO. "This great progress is underpinned by our focus on financial discipline, resulting in positive third-quarter and year-to-date net income. As we close out the year, we will continue driving momentum in our commercial portfolio and hematology and oncology development pipeline."

Third Quarter 2024 Business Update

Commercial Update

Commercial strength continues for all products with record bottles shipped to patients and clinics and total bottles sold.
GAVRETO became commercially available from Rigel in June 2024. Third-quarter results reflect the successful transition of existing patients on therapy to Rigel’s product. For the fourth quarter, the focus will be on continuing to transition patients.
The following table summarizes total bottles shipped for the third quarter:

TAVALISSE

REZLIDHIA

GAVRETO*

Bottles shipped to patients and clinics

2,797

444

717

Change in bottles remaining in distribution channel

(4)

(15)

35

Total bottles shipped

2,793

429

752

*GAVRETO bottle count represents 60-count bottle equivalent

In September, Rigel entered into an exclusive license and supply agreement with Kissei Pharmaceutical Co., Ltd. ("Kissei") to develop and commercialize REZLIDHIA in all potential indications in Japan, the Republic of Korea and Taiwan. Under the terms of the agreement, Rigel received an upfront cash payment of $10.0 million from Kissei, with the potential for up to an additional $152.5 million in development, regulatory and commercial milestone payments.
In late October, Rigel issued a Dear Health Care Provider (DHCP) letter related to a new safety signal for GAVRETO after consultation with the U.S. Food and Drug Administration (FDA). The DHCP letter has been posted to the GAVRETO Healthcare Provider website at www.gavreto-hcp.com.
Clinical and Development Update

Rigel continues to advance its Phase 1b clinical study evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of R2891, a novel and selective dual IRAK1/4 inhibitor, in patients with R/R lower-risk myelodysplastic syndrome (LR-MDS). Enrollment in the fifth dose level (500mg / 250mg split dose) is underway.
In early November, Rigel announced six poster presentations highlighting data from the company’s commercial and clinical-stage hematology and oncology portfolio at the upcoming 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. Initial data from the ongoing Phase 1b study evaluating R289 in patients with R/R LR-MDS indicate that R289 was generally well tolerated in a heavily pretreated LR-MDS patient population, the majority of whom were high transfusion burden at study entry. As of the data cutoff, 14 of 19 patients were evaluable for efficacy and per International Working Group (IWG) 2018, RBC-transfusion independence (RBC-TI)/hematologic improvement (HI-E) occurred in 36% of patients receiving R289 doses ≥500 mg QD, with a median duration of RBC-TI of 29 weeks. RBC-TI >24 weeks was achieved in 2 high transfusion burden patients following 3 and 5 prior therapies, including a hypomethylating agent. The company will also present additional data for olutasidenib in patients with R/R mIDH1 AML and MDS.
In September, Rigel announced the first patient was enrolled in a Phase 1b/2 triplet therapy trial of decitabine and venetoclax in combination with REZLIDHIA in patients with mIDH1 AML, which is being sponsored and conducted by The University of Texas MD Anderson Cancer Center (MD Anderson). This is the first trial in Rigel’s multi-year strategic development alliance with MD Anderson.
A paper detailing the differences in molecular structure, binding characteristics and clinical outcomes between olutasidenib and ivosidenib, including response rates in patients previously treated with ivosidenib or venetoclax, was published by Dr. Justin M. Watts, Associate Professor of Medicine, Division of Hematology, Chief, Leukemia Section at the University of Miami Health System, in Current Treatment Options in Oncology in October 2024.
Third Quarter 2024 and Year-To-Date Financial Update
For the third quarter ended September 30, 2024, total revenues were $55.3 million, consisting of $26.3 million in TAVALISSE net product sales, $5.5 million in REZLIDHIA net product sales, $7.1 million in GAVRETO net product sales, and $16.4 million in contract revenue from collaborations. TAVALISSE net product sales grew 8% compared to $24.5 million in the same period of 2023. REZLIDHIA net product sales grew 107% compared to $2.7 million in the same period of 2023. GAVRETO became commercially available from Rigel in June 2024. Contract revenue from collaborations consisted of $13.0 million from Kissei Pharmaceutical Co., Ltd. (Kissei) related to an upfront fee from sublicensing olutasidenib and delivery of drug supplies, as well as $3.3 million from Grifols S.A. (Grifols) and $0.1 million from Medison Pharma Trading AG (Medison) related to delivery of drug supplies and earned royalties.

Total costs and expenses were $41.3 million compared to $32.6 million for the same period of 2023. The increase in costs and expenses was mainly due to higher cost of product sales, driven primarily by increased products sales, a sublicensing revenue fee to Forma, increased royalties and amortization of intangible assets. In addition, there were increases in personnel-related costs and commercial-related expenses.

Rigel reported net income of $12.4 million, or $0.71 basic and $0.70 diluted per share, compared to a net loss of $5.7 million, or $0.33 basic and diluted per share, for the same period of 2023. The basic and diluted share and per share amounts for the prior period have been restated to reflect the 1-for-10 reverse stock split effected on June 27, 2024 on a retroactive basis.

For the nine months ended September 30, 2024, total revenues were $121.7 million, consisting of $73.8 million in TAVALISSE net product sales, $15.6 million in REZLIDHIA net product sales, $9.0 million in GAVRETO net product sales, and $23.3 million in contract revenue from collaborations. TAVALISSE net product sales grew 8% compared to $68.1 million in the same period of 2023. REZLIDHIA net product sales grew 133% compared to $6.7 million in the same period of 2023. As mentioned above, GAVRETO became commercially available from Rigel in June 2024. Contract revenue from collaborations consisted of $17.5 million from Kissei related to an upfront fee from sublicensing olutasidenib and delivery of drug supplies, as well as $5.5 million from Grifols and $0.2 million from Medison related to delivery of drug supplies and earned royalties.

Total costs and expenses were $114.1 million compared to $103.5 million for the same period of 2023. The increase in costs and expenses was mainly due to higher cost of product sales driven primarily by increased products sales, a sublicensing revenue fee to Forma, increased royalties and amortization of intangible assets. In addition, there were increases in personnel-related costs, stock-based compensation expense and commercial-related expenses. These increases were partially offset by decreased research and development costs due to the timing of clinical trial activities related to R289, the company’s dual IRAK 1/4 inhibitor program, as well as reduced trial activities related to the completed Phase 3 clinical trials of fostamatinib in patients with COVID-19 and in patients with warm antibody hemolytic anemia (wAIHA).

Rigel reported net income of $3.1 million, or $0.18 basic and diluted per share, compared to a net loss of $25.8 million, or $1.49 basic and diluted per share, for the same period of 2023. As discussed above, the share and per share amounts for the prior period have been restated to reflect the 1-for-10 reverse stock split on a retroactive basis for the periods presented.

Cash, cash equivalents and short-term investments as of September 30, 2024 was $61.1 million, compared to $49.1 million as of June 30, 2024, and $56.9 million as of December 31, 2023.

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 there will be about 20,800 new cases in the United States, most in adults, in 2024.2

Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.3 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.4 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 NSCLC
It is estimated that over 230,000 adults in the U.S. will be diagnosed with lung cancer in 2024. Lung cancer is the leading cause of cancer death in the U.S, with NSCLC being the most common type accounting for 80-85% of all lung cancer diagnoses.5 RET fusions are implicated in approximately 1-2% of patients with NSCLC.6

About TAVALISSE
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.

Please click here for Important Safety Information and Full Prescribing Information for TAVALISSE.

About REZLIDHIA
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.

Please click here for Important Safety Information and Full Prescribing Information, including Boxed WARNING, for REZLIDHIA.

About GAVRETO
GAVRETO is indicated for the treatment of adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved test and adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).*

*Thyroid indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

Please click here for Important Safety Information and Full Prescribing Information for GAVRETO.

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, REZLIDHIA and GAVRETO are registered trademarks of Rigel Pharmaceuticals, Inc.

On November 7, 2024 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported financial results for the third quarter ended September 30, 2024 (Press release, Repare Therapeutics, NOV 7, 2024, View Source [SID1234647946]).

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"We look forward to reporting data from our MYTHIC dose expansion clinical trial evaluating lunresertib in combination with camonsertib at the recommended Phase 2 dose at a company event in December, with the plan to begin a registrational trial in 2025. This combination therapy has the potential to be a new treatment paradigm in genomically-defined platinum-resistant ovarian cancer and second-line endometrial cancer," said Lloyd M. Segal, President and CEO of Repare. "In the third quarter, we continued to make progress across our pipeline, including the dosing of the first patient in the POLAR clinical trial evaluating RP-3467, alone and in combination with the PARP inhibitor, olaparib. Additionally, we presented first-in-human data highlighting the clinical benefits of camonsertib in combination with radiotherapy at the ASTRO annual meeting in collaboration with investigators at Memorial-Sloan Kettering Cancer Center."

Third Quarter 2024 and Recent Portfolio Highlights:

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Lunresertib (RP-6306): First-in-class, oral PKMYT1 inhibitor
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Currently evaluating lunresertib in combination with camonsertib in Repare’s MYTHIC dose expansion clinical trial at the RP2D in patients with platinum-resistant ovarian and endometrial cancers harboring CCNE1 amplification or FBXW7 or PPP2R1A mutations, which are predictive of poor prognosis. Repare is on track to report data from approximately 20-30 patients in each cohort in December 2024, with the plan to begin a registrational trial in 2025.
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Presented positive updated safety and tolerability data from the Phase 1 MYTHIC trial at the RP2D highlighting the benefits of its individualized schedule for the management of anemia at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in October 2024. In this analysis, Repare followed patients for approximately nine months at the RP2D to assess the effectiveness of an individualized schedule. The analysis demonstrated a successful approach to mitigating mechanism-based anemia while maintaining clinical benefit. No thrombocytopenia of any grade nor serious neutropenia in these patients was observed. Dose optimization meaningfully reduced Grade 3 anemia to 22.6% from 51.4% in all patients.
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Presented data at the American Association of Cancer Research’s (AACR) (Free AACR Whitepaper) 15th Annual Ovarian Cancer Research Symposium in September 2024 highlighting the impact of alterations in FBXW7, PPP2R1A and CCNE1 in patients with metastatic ovarian and endometrial cancers based on an analysis in approximately 2,000 patients from Cancer Genome Atlas Research Network and Memorial Sloan Kettering’s Metastatic Events and Tropisms. The data underscores inherent chemotherapy resistance and the lack of treatment options for metastatic gynecologic cancer patients with these biomarkers.
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Evaluating lunresertib in combination with Debio 0123, a highly selective, brain-penetrant, clinical WEE1 inhibitor, in Module 4 of the ongoing MYTHIC clinical trial in patients with advanced solid tumors harboring CCNE1 amplification or FBXW7 or PPP2R1A deleterious alterations. Repare expects to report initial data from Module 4 of the MYTHIC trial in 2025.
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Camonsertib (RP-3500): Potential best-in-class oral ATR inhibitor
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Evaluating camonsertib as a monotherapy in the ongoing non-small cell lung cancer (NSCLC) expansion of the Phase 2 TRESR clinical trial. Camonsertib has demonstrated a promising signal of prolonged progression free survival in patients with ATM-mutated NSCLC in the TRESR clinical trial. Repare expects to report initial data from the TRESR clinical trial in 2025.
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Presented Phase 1 data from a clinical trial conducted in collaboration with investigators at Memorial-Sloan Kettering Cancer Center highlighting camonsertib in combination with palliative radiation for the treatment of metastatic tumors harboring an ataxia-telangiectasia-mutated (ATM) mutation at the American Society for Radiation Oncology (ASTRO) annual meeting in September 2024. The first-in-human data showed that the combination demonstrated higher clinical benefit in patients with tumors harboring pathogenic ATM mutations versus those with variants of unknown significance.
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RP-1664: First-in-class, oral, selective PLK4 inhibitor
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Evaluating RP-1664 as a monotherapy in the Phase 1 LIONS clinical trial in adult and adolescent patients with TRIM37-high solid tumors, including the recent dosing of the first adolescent patient with neuroblastoma. After evaluating safety in the LIONS clinical trial, the Company expects to rapidly advance RP-1664 into a Phase 1/2 trial in pediatric patients with high risk, recurrent neuroblastoma, where the patients have a high prevalence of TRIM37-altered tumors.
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RP-3467: Potential best-in-class, oral Polθ ATPase inhibitor
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Dosed the first patient in the POLAR clinical trial evaluating RP-3467, a Polθ ATPase inhibitor, alone and in combination with the poly-ADP ribose polymerase (PARP) inhibitor, olaparib. The POLAR clinical trial is a multicenter, open-label, dose-escalation Phase 1 clinical trial to investigate the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of RP-3647 alone or in combination with olaparib in adults with molecularly selected advanced solid tumors. The trial is expected to enroll patients with locally advanced or metastatic epithelial ovarian cancer, metastatic breast cancer, metastatic castration-resistant prostate cancer, or pancreatic adenocarcinoma.
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Other Company Updates
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In August 2024, Repare announced a strategic reprioritization of its research and development activities to focus its efforts on the advancement of its portfolio of clinical-stage oncology programs.

As part of this strategic refocus, Repare reduced its overall workforce by approximately 25%, with a majority of the headcount reductions from its preclinical group.
Third Quarter 2024 Financial Results:

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Cash, cash equivalents and marketable securities: Cash, cash equivalents and marketable securities as of September 30, 2024 were $179.4 million. The Company believes that its cash, cash equivalents, and marketable securities are sufficient to fund its current operational plans into the second half of 2026.
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Revenue from collaboration agreements: Revenue from collaboration agreements were nil and $53.5 million for the three and nine months ended September 30, 2024, respectively, as compared to $2.2 million and $38.1 million for the three and nine months ended September 30, 2023.
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Research and development expenses, net of tax credits (Net R&D): Net R&D expenses were $28.4 million and $91.4 million for the three and nine months ended September 30, 2024, respectively, as compared to $32.7 million and $98.3 million for the three and nine months ended September 30, 2023.
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General and administrative (G&A) expenses: G&A expenses were $6.4 million and $23.4 million for the three and nine months ended September 30, 2024, respectively, compared to $7.9 million and $25.1 million for the three and nine months ended September 30, 2023.
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Net loss: Net loss was $34.4 million, or $0.81 per share, and $56.0 million, or $1.32 per share, in the three and nine months ended September 30, 2024, respectively, compared to $18.9 million, or $0.45 per share, and $65.8 million, or $1.56 per share, three and nine months ended September 30, 2023, respectively.

On November 7, 2024 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported financial results for the third quarter ended September 30, 2024 (Press release, Puma Biotechnology, NOV 7, 2024, View Source [SID1234647945]). Unless otherwise stated, all comparisons are for the third quarter of 2024 compared to the third quarter of 2023.

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Product revenue, net consists entirely of sales revenue from NERLYNX, Puma’s first commercial product. Product revenue, net in the third quarter of 2024 was $56.1 million, compared to $51.6 million in the third quarter of 2023. Product revenue, net in the first nine months of 2024 was $140.8 million, compared to $149.9 million in the first nine months of 2023.

Based on accounting principles generally accepted in the United States (GAAP), Puma reported net income of $20.3 million, or $0.41 per basic and diluted share, for the third quarter of 2024, compared to a net income of $5.8 million, or $0.12 per basic and diluted share, for the third quarter of 2023. Net income for the first nine months of 2024 was $11.0 million, or $0.23 per basic share and $0.22 per diluted share, compared to net income of $9.3 million, or $0.20 per basic and diluted share, for the first nine months of 2023.

Non-GAAP adjusted net income was $22.4 million, or $0.46 per basic share and $0.45 per diluted share, for the third quarter of 2024, compared to $8.3 million, or $0.18 per basic share and $0.17 per diluted share, for the third quarter of 2023. Non-GAAP adjusted net income for the first nine months of 2024 was $17.5 million, or $0.36 per basic and diluted share, compared to non-GAAP adjusted net income of $17.1 million, or $0.36 per basic and diluted share, for the first nine months of 2023. Non-GAAP adjusted net income excludes stock-based compensation expenses. For a reconciliation of GAAP net income to non-GAAP adjusted net income and GAAP net income per share to non-GAAP adjusted net income per share, please see the financial tables at the end of this news release.

Net cash provided by operating activities for the third quarter of 2024 was $11.0 million, compared to $10.7 million in the third quarter of 2023. Net cash provided by operating activities for the first nine months of 2024 was $23.3 million, compared to net cash provided by operating activities of $16.6 million in the first nine months of 2023. On September 30, 2024, Puma had cash, cash equivalents and marketable securities of approximately $97 million, compared to cash, cash equivalents, and marketable securities of approximately $96 million at December 31, 2023.

"We are pleased to announce both positive net income and positive operating cash flow for the third quarter of 2024," said Alan H. Auerbach, Chairman, Chief Executive Officer, and President of Puma. "In addition to our focus on the commercialization of NERLYNX, we are also continuing to make progress with the clinical development of alisertib for patients with extensive stage small cell lung cancer and patients with chemotherapy-naïve HER2-negative, hormone receptor-positive metastatic breast cancer."

Mr. Auerbach added, "We anticipate the following key milestones over the next 12 months: (i) initiation of ALI-1201/ALISCA-Breast1, a Phase II trial of alisertib in combination with endocrine treatment in patients with chemotherapy-naïve HER2-negative, hormone receptor-positive metastatic breast cancer (Q4 2024); (ii) presentation of interim data from ALI-4201/ALISCA-Lung1, a Phase II clinical trial of alisertib monotherapy for the treatment of patients with extensive stage small cell lung cancer (2025); and (iii) presentation of interim data from ALISCA-Breast1, a Phase II trial of alisertib in combination with endocrine treatment in patients with chemotherapy-naïve HER2-negative, hormone receptor-positive metastatic breast cancer (2025)."

Revenue

Total revenue consists of product revenue, net from sales of NERLYNX, Puma’s first commercial product and royalty revenue. For the third quarter of 2024, total revenue was $80.5 million, of which $56.1 million was product revenue, net and $24.4 million was royalty revenue. This compares to total revenue of $56.1 million in the third quarter of 2023, of which $51.6 million was product revenue, net and $4.5 million was royalty revenue. For the first nine months of 2024, total revenue was $171.4 million, of which $140.8 million was product revenue, net and $30.6 million was royalty revenue. This compares to total revenue of $163.5 million for the first nine months of 2023, of which $149.9 million was product revenue, net, and $13.6 million was royalty revenue.

Operating Costs and Expenses

Total operating costs and expenses were $58.4 million for the third quarter of 2024, compared to $47.5 million for the third quarter of 2023. Operating costs and expenses in the first nine months of 2024 were $153.8 million, compared to $145.7 million in the first nine months of 2023.

Cost of Sales

Cost of sales was $29.1 million for the third quarter of 2024, compared to $13.3 million for the third quarter of 2023. Cost of sales was $50.5 million for the first nine months of 2024, compared to $38.4 million for the first nine months of 2023. The increase was primarily due to royalty expense related to the timing of sales made in China by our sub-licensee and an increase in units shipped to China.

Selling, General and Administrative Expenses

Selling, general and administrative (SG&A) expenses were $16.8 million for the third quarter of 2024, compared to $22.8 million for the third quarter of 2023. SG&A expenses for the first nine months of 2024 were $63.5 million, compared to $69.7 million for the first nine months of 2023. The $6.2 million decrease in SG&A expenses for the first nine months of 2024 compared to the first nine months of 2023 resulted from a decrease in payroll and related costs of approximately $2.4 million, primarily due to lower headcount, partially offset by annual salary increases; and a decrease in professional fees and expenses of approximately $1.2 million, primarily due to decreases of approximately $3.2 million in marketing expenses and $0.4 million in insurance and other expenses. These decreases were partially offset by an increase of approximately $2.3 million in legal fees; a decrease in stock-based compensation expense of approximately $1.1 million, primarily due to lower headcount; a decrease in provision for credit loss of $0.6 million, due to a customer payment on an overdue receivable; and a decrease in loss on impairment of asset expense of approximately $0.6 million in connection with our decision to sublease a portion of our office space in 2023.

Research and Development Expenses

Research and development (R&D) expenses were $12.5 million for the third quarter of 2024, compared to $11.4 million for the third quarter of 2023. R&D expenses for the first nine months of 2024 were $39.8 million, compared to $37.6 million for the first nine months of 2023. The $2.2 million year-over-year increase in R&D expenses resulted primarily from an increase in clinical trial expenses of approximately $1.8 million, primarily due to the procurement of alisertib drug product and increased alisertib study activity, partially offset by fewer clinical milestones being achieved, and an increase in internal R&D expenses of approximately $0.8 million, primarily due to one-time payroll and severance related expenses.

Total Other Income (Expenses)

Total other expenses were $1.5 million for the third quarter of 2024, compared to $2.6 million for the third quarter of 2023. Total other expenses of $5.7 million for the first nine months of 2024 were down from $8.0 million for the first nine months of 2023 due primarily to an increase in interest income.

Fourth Quarter and Full Year 2024 Financial Outlook

Fourth Quarter 2024

Full Year 2024 (previous)

Full Year 2024 (new)

Net Product Revenue

$46–$48 million

$183–$190 million

$187–$190 million

Royalty Revenue

$3.5–$5 million

$30–$34 million

$34–$36 million

License Revenue

$1–$2 million

$1–$2 million

$1–$2 million

Net Income

$4–$6 million

$12–$15 million

$15–$17 million

Gross to Net Adjustment

21%–22%

21%–22%

20.5%–21.5%

Conference Call

Puma Biotechnology will host a conference call to report its third quarter 2024 financial results and provide an update on Puma’s business and outlook at 1:30 p.m. PST/4:30 p.m. EST on Thursday, November 7, 2024. The call may be accessed by dialing 1 (877) 709-8150 (domestic) or 1 (201) 689-8354 (international). Please dial in at least 10 minutes in advance and inform the operator that you would like to join the "Puma Biotechnology Conference Call." A live webcast of the conference call and presentation slides may be accessed on the Investors section of the Puma Biotechnology website at View Source A replay of the call will be available shortly after completion of the call and will be archived on Puma’s website for 90 days.