On February 28, 2024 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company developing investigational first-in-class telomerase inhibitor, imetelstat, to treat hematologic malignancies, reported business highlights and financial results for the fourth quarter and full year 2023 (Press release, Geron, FEB 28, 2024, View Source [SID1234640582]).

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"Geron’s progress and execution throughout 2023 has paved the way for a potentially transformational 2024, as we plan for the transition to becoming a commercial company," said John A. Scarlett, M.D., Chairman and Chief Executive Officer. "We believe that we are in a strong position for value creation, based on our differentiated product candidate, the potential for significant commercial opportunities in transfusion-dependent, lower-risk MDS and relapsed/refractory MF, the excellence and experience of our employees, and the strength of our balance sheet to support a potential U.S. launch."

2023 Business Highlights

Transfusion-Dependent Lower-Risk Myelodysplastic Syndromes (TD LR-MDS)

In January 2023, Geron reported positive top-line results from the pivotal IMerge Phase 3 clinical trial evaluating imetelstat in patients with TD LR-MDS. Additional data including subgroup analyses and patient-reported outcomes were subsequently reported at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting in June 2023 and at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and published in The Lancet in December 2023.
In August 2023, the U.S. Food & Drug Administration (FDA) accepted the New Drug Application (NDA) for imetelstat for the treatment of TD anemia in adult patients with low- to intermediate-1 risk myelodysplastic syndromes, who have failed to respond, or have lost response to, or are ineligible for erythropoiesis-stimulating agents (ESAs). The FDA assigned a Prescription Drug User Fee Act (PDUFA) action date of June 16, 2024 to the NDA.
On January 30, 2024, the FDA provided notice in the Federal Register that it has scheduled a public Oncologic Drugs Advisory Committee to be held virtually on March 14, 2024, as part of the imetelstat NDA review.
In September 2023, the European Medicines Agency (EMA) validated the Marketing Authorization Application (MAA) for imetelstat in the same proposed indication as the NDA.
Myelofibrosis

In December 2023, Geron achieved fifty percent enrollment in the Phase 3 IMpactMF clinical trial investigating imetelstat versus best available therapy (BAT) in patients with intermediate-2 or high-risk Myelofibrosis (MF) who are relapsed/refractory myelofibrosis (R/R MF) to Janus kinase (JAK) inhibitor treatment.
In January 2024, dosing in the Phase 1 IMproveMF study evaluating imetelstat as a combination therapy with ruxolitinib in patients with intermediate-2 or high-risk MF (frontline MF) was escalated to the third of four doses following a decision by the study’s independent Safety Evaluation Team (SET).
Corporate

In November 2023, Geron appointed Gaurav Aggarwal, M.D., a prominent investor in the life sciences sector for more than two decades who has a history of expertise in financial and corporate strategy, as well as business development, to Geron’s Board of Directors.
In August and September 2023, respectively, Geron appointed Scott Samuels as Executive Vice President, Chief Legal Officer and Corporate Secretary, and Michelle Robertson as Executive Vice President, Chief Financial Officer and Treasurer. Both Mr. Samuels and Ms. Robertson join Geron with a track record of excellence in commercial-stage biopharmaceutical companies.
Anticipated Upcoming Milestones

U.S. commercial launch of imetelstat upon potential FDA approval (PDUFA date June 16, 2024) for the treatment of transfusion-dependent anemia in adult patients with LR-MDS who have failed to respond, or have lost response to, or are ineligible for ESAs.
Review of the imetelstat MAA for the same indication as the NDA expected to be completed in early 2025. Subject to approval by the European Commission, EU commercial launch of imetelstat could occur in 2025.
Interim analysis from the Phase 3 IMpactMF trial in R/R MF expected in the first half of 2025, with a final analysis from the study expected in the first half of 2026.
U.S. Commercial Preparation

Throughout 2023, Geron completed several long-lead time pre-commercial activities, including securing a global trademark for the imetelstat brand name; finalizing third party logistics, our distribution network, patient support providers; and onboarding highly experienced commercial and medical affairs teams. Other pre-commercial preparations for the U.S. are ongoing, including enhancing and/or establishing company processes and systems to support an expected commercial launch, refining our market research in TD LR-MDS, and engaging in marketing, commercial access, payer, and reimbursement preparatory efforts.

Fourth Quarter and Full Year 2023 Financial Results

As of December 31, 2023, the Company had $378.1 million in cash, cash equivalents, and marketable securities. During 2023, the Company received net cash proceeds of $213.3 million from the underwritten public offering of common stock and pre-funded warrants completed in January 2023, $105.9 million of cash proceeds from the exercise of outstanding warrants, and $29.7 million in net proceeds drawn down under the Loan Agreement with Hercules and SVB in the fourth quarter of 2023. Based on the Company’s current operating plans and expectations regarding the expected timing of regulatory approval and commercialization of imetelstat in the U.S. in the first half of 2024, Geron projects that its existing financial resources, together with projected revenues from U.S. sales of imetelstat, proceeds from the exercise of outstanding warrants, and funding under the Company’s loan facility, will be sufficient to fund its projected operating expenses into the third quarter of 2025.

Revenues for the three and twelve months ended December 31, 2023, were $23,000 and $237,000, respectively, compared to $103,000 and $596,000 for the comparable 2022 periods. Revenues in both years primarily reflect estimated royalties from sales of cell-based research products from the Company’s divested stem cell assets.

Total operating expenses for the three and twelve months ended December 31, 2023, were $54.3 million and $194.1 million, respectively, compared to $42.0 million and $139.1 million for the comparable 2022 periods.

Research and development expenses for the three and twelve months ended December 31, 2023, were $32.9 million and $125.0 million, respectively, compared to $28.2 million and $95.5 million for the comparable 2022 periods. The increase in research and development expenses for the three and twelve months ended December 31, 2023, compared to the same periods in 2022, primarily reflects higher clinical trial costs related to supporting the Company’s IMerge and IMpactMF Phase 3 clinical trials, increased personnel-related expenses for additional headcount in preparation for transition to a commercial-stage company, higher consulting costs to support regulatory submissions, and greater manufacturing costs in preparation for potential commercialization.

General and administrative expenses for the three and twelve months ended December 31, 2023, were $21.4 million and $69.1 million, respectively, compared to $13.8 million and $43.6 million for the comparable 2022 periods. The increase in general and administrative expenses for the three and twelve months ended December 31, 2023, compared to the same periods in 2022, primarily reflects additional costs for commercial preparatory activities and higher personnel-related expenses for additional headcount in preparation for transition to a commercial-stage company.

Interest income was $4.6 million and $18.2 million for the three and twelve months ended December 31, 2023, respectively, compared to $1.2 million and $2.5 million for the same periods in 2022. The increase in interest income for the three and twelve months ended December 31, 2023, compared to the same periods in 2022, primarily reflects higher yields on the Company’s marketable securities as a result of higher interest rates, as well as a larger investment portfolio with the cash proceeds from the January 2023 public offering and warrant exercises in 2023.

Interest expense was $2.3 million and $8.3 million for the three and twelve months ended December 31, 2023, respectively, compared to $2.0 million and $6.8 million for the same periods in 2022. The increase in interest expense for the three and twelve months ended December 31, 2023, compared to the same periods in 2022, primarily reflects higher interest rates. Currently, the Company has $80.0 million in principal debt outstanding and $45.0 million available under its existing loan facility, subject to achievement of specified milestones or approval of the lenders.

Projected 2024 Financial Guidance

For fiscal year 2024, the Company expects total operating expenses to be in the range of approximately $270 million to $280 million, which includes non-cash items such as stock-based compensation expense, amortization of debt discounts and issuance costs, and depreciation and amortization.

The fiscal year 2024 financial guidance reflects costs to support regulatory processes with the FDA and EMA in 2024; continued support of ongoing clinical trials; manufacturing of commercial inventory of imetelstat; continued build out of our commercial organization to support the potential U.S. commercial launch of imetelstat S; continued increases in headcount in preparation for transition to a commercial-stage company; and interest payments on outstanding debt.

As of December 31, 2023, the Company had 141 full-time employees. Subject to approval of imetelstat in the U.S., the Company plans to grow to a total of approximately 270 employees by year-end 2024.

Conference Call

Geron will host a conference call at 8:00 am ET on Wednesday, February 28, 2024, to discuss business updates and fourth quarter and full year 2023 financial results.

A live webcast of the conference call and related presentation will be available on the Company’s website at www.geron.com/investors/events. An archive of the webcast will be available on the Company’s website for 30 days.

Participants may access the webcast by registering online using the following link, View Source

About Imetelstat

Imetelstat is a novel, first-in-class investigational telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from non-clinical studies and clinical trials of imetelstat provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies, resulting in malignant cell apoptosis and suggesting potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the U.S. Food and Drug Administration for both the treatment of adult patients with transfusion dependent anemia due to Low or Intermediate-1 risk MDS that is not associated with del(5q) who are refractory or resistant to an erythropoiesis stimulating agent, and for adult patients with Intermediate-2 or High-risk myelofibrosis (MF) whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment. Imetelstat is currently not approved by any regulatory authority.

About IMerge Phase 3

The Phase 3 portion of the IMerge Phase 2/3 study is a double-blind, 2:1 randomized, placebo-controlled clinical trial to evaluate imetelstat in patients with IPSS Low or Intermediate-1 risk (lower risk) transfusion dependent MDS who were relapsed after, refractory to, or ineligible for, erythropoiesis stimulating agent (ESA) treatment, had not received prior treatment with either a HMA or lenalidomide and were non-del(5q). To be eligible for IMerge Phase 3, patients were required to be transfusion dependent, defined as requiring at least four units of packed red blood cells (RBCs), over an eight-week period during the 16 weeks prior to entry into the trial. The primary efficacy endpoint of IMerge Phase 3 is the rate of red blood cell transfusion independence (RBC-TI) lasting at least eight weeks, defined as the proportion of patients without any RBC transfusion for at least eight consecutive weeks since entry to the trial (8-week TI). Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks (24-week TI), the duration of TI and the rate of hematologic improvement erythroid (HI-E), which is defined under 2006 IWG criteria as a rise in hemoglobin of at least 1.5 g/dL above the pretreatment level for at least eight weeks or a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden. A total of 178 patients were enrolled in IMerge Phase 3 across North America, Europe, Middle East and Asia.

About IMpactMF Phase 3

IMpactMF is an open label, randomized, controlled Phase 3 clinical trial with registrational intent. The trial is designed to enroll approximately 320 patients with intermediate-2 or high-risk MF who are relapsed after or refractory to prior treatment with a JAK inhibitor, also referred to as R/R MF. Patients will be randomized to receive either imetelstat or BAT. The primary endpoint is overall survival (OS). Key secondary endpoints include symptom response, spleen response, progression-free survival, complete remission, partial remission, clinical improvement, duration of response, safety, pharmacokinetics, and patient reported outcomes.

About IMproveMF

IMproveMF is a single arm, open label, two-part Phase 1 study to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of imetelstat in combination with ruxolitinib as a frontline treatment in patients with Intermediate-2 or High-risk MF (frontline MF). In both parts, patients will receive ruxolitinib followed by imetelstat, a dosing schedule that showed synergistic and additive effects of the two agents in preclinical experiments. Part 1 will enroll up to 20 frontline MF patients who, at the time of enrollment, have received an optimized dose of ruxolitinib, to which imetelstat treatment will be added at increasing dose levels based on safety and tolerability. The primary purpose of Part 1 is to identify a safe dose for treating frontline MF patients with a combination of imetelstat and ruxolitinib. If a safe dose is identified in Part 1, participants in Part 2 will be JAK inhibitor naïve and will receive treatment with ruxolitinib after screening and enrollment at a starting dose based on standard of care or local prescribing information. Treatment with single-agent ruxolitinib will continue for at least 12 weeks, including four consecutive weeks at a stable dose prior to the addition of imetelstat. Part 2 is designed to confirm the safety profile of imetelstat in combination with ruxolitinib and to evaluate for preliminary clinical activity of the combination.

On February 28, 2024 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported a corporate and financial update for the fourth quarter and full year ended December 31, 2023 (Press release, G1 Therapeutics, FEB 28, 2024, View Source [SID1234640581]).

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"The strong fourth quarter 2023 vial volume growth of COSELA, which has continued through the beginning of 2024, highlights not only the importance of this unique drug to oncologists treating people living with extensive-stage small cell lung cancer, but also the significant addressable market still available to us as we drive continued penetration and growth," said Jack Bailey, Chief Executive Officer of G1 Therapeutics. "Looking ahead, our primary clinical focus is on completing our ongoing trials of trilaciclib in metastatic triple negative breast cancer, including our pivotal PRESERVE 2 trial. We remain confident in the potential of trilaciclib in this trial given the robust long term survival benefit observed in prior trials and the increased statistical power for the final analysis. If successful, we would work closely with the U.S. Food and Drug Administration to expeditiously file for label expansion and bring this therapy to patients as quickly as possible."

Fourth Quarter 2023 and Recent Highlights

Financial

Recognized $13.9 Million and $46.3 Million in Net COSELA Revenue for the Fourth Quarter and Full Year 2023: Net COSELA revenue and vial volume grew 29% and 19%, respectively, during the fourth quarter over the third quarter of 2023 despite the impact of a platinum-based chemotherapy shortage. G1 recognized total revenues of $14.9 million and $82.5 million for the fourth quarter and full year of 2023, respectively.
Cash Runway Extends into 2025: G1 ended 2023 with cash, cash equivalents, and marketable securities of $82.2 million.
Clinical

Final Analysis of the Phase 3 PRESERVE 2 Trial in Metastatic Triple Negative Breast Cancer (mTNBC) is Estimated to Occur in the Third Quarter of 2024: G1 announced that the Independent Data Monitoring Committee (DMC) recommended continuation of the Phase 3 PRESERVE 2 trial, evaluating trilaciclib in combination with gemcitabine and carboplatin for 1L treatment of mTNBC, to the final analysis. The DMC did not express any concerns or recommend any other changes to the study. The final analysis will be conducted on the intent-to-treat (ITT) population. G1 remains blinded to all data. (See February 12, 2024 press release here)
Initial Efficacy Results from Ongoing Phase 2 Antibody-Drug Conjugate (ADC) Trial Suggest Improved Overall Survival (OS) Among Patients Receiving Trilaciclib in Combination with a TROP2 ADC: The preliminary data provided in January 2024 from the ongoing Phase 2 trial of trilaciclib in combination with the ADC sacituzumab govitecan (SG) in patients with mTNBC patients suggested clinically meaningful improvements in OS among patients receiving trilaciclib in combination with SG compared to SG alone (using historical data from the ASCENT study), including (1) median OS of 17.9 months with trilaciclib versus 12.1 months for SG alone and (2) estimated 12-month survival of 59% of patients receiving trilaciclib in combination with SG, representing a ~20% improvement over SG alone. The Company expects to provide updated OS results from this study mid-2024. (See January 8, 2024 J.P. Morgan update press release here)
Medical

Presented New Post Hoc Analyses Indicating that Patients Who Previously Received Trilaciclib Experienced Improved OS with Subsequent Anticancer Therapies (SACT): G1 presented new data at the 2023 San Antonio Breast Cancer Symposium (SABCS) from patients with mTNBC who participated in G1’s Phase 2 trial. These data indicate that patients who received trilaciclib with their cytotoxic chemotherapy during the trial and then received SACT after trilaciclib discontinuation exhibit statistically significant and clinically meaningful improvements in median OS (32.7 months versus 12.8 months; p=0.001). Additionally, median OS for patients who received prior trilaciclib was improved from the time they started their first SACT compared to patients who did not receive prior trilaciclib (14.0 months versus 5.8 months; p=0.001). (See December 5, 2023 SABCS press release here)
Presented Four Posters During the 2023 ASCO (Free ASCO Whitepaper) Quality Care Symposium: These provide new real-world evidence indicating that trilaciclib administered prior to chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC) lowers the rate of hospitalization and cytopenia events and may improve survival. (See October 27, 2023 ASCO (Free ASCO Whitepaper) Quality Care Symposium press release here)
COSELA Recommended as a Myeloid Supportive Agent in the Updated ASCO (Free ASCO Whitepaper) SCLC Guidelines: The SCLC guidelines provide evidence-based recommendations to practicing clinicians on the management of patients with SCLC. (See October 18, 2023 ASCO (Free ASCO Whitepaper) Guidelines press release here)
Fourth Quarter and Full Year 2023 Financial Results

As of December 31, 2023, cash, cash equivalents and marketable securities totaled $82.2 million, compared to $145.1 million as of December 31, 2022.

Total revenues for the fourth quarter of 2023 were $14.9 million, including $13.9 million in net product sales of COSELA and license revenue of $1.0 million, primarily related to supply and manufacturing services from Simcere and patent and clinical trial costs reimbursed primarily by EQRx and Simcere, compared to $10.3 million in total revenues in the fourth quarter of 2022. Total revenues for the full year 2023 were $82.5 million, including net product revenue of $46.3 million from sales of COSELA and license revenue of $36.2 million, compared to total revenues of $51.3 million in the prior year.

Operating expenses for the fourth quarter of 2023 were $23.8 million, compared to $41.1 million for the fourth quarter of 2022. GAAP operating expenses include stock-based compensation expense of $3.2 million for the fourth quarter of 2023, compared to $4.4 million for the fourth quarter of 2022. Operating expenses for the full year 2023 were $122.0 million, compared to $187.5 million for the prior year. Stock-based compensation expense for the full year 2023 was $14.5 million, compared to $20.6 million for the prior year.

Cost of goods sold expense for the fourth quarter of 2023 was $1.3 million, compared to $1.0 million for the fourth quarter of 2022, primarily due to an increase in product sales. Cost of goods sold expense for the full year 2023 was $7.2 million, compared to $3.7 million for the prior year.

Research and development (R&D) expenses for the fourth quarter of 2023 were $7.4 million, compared to $16.6 million for the fourth quarter of 2022. The decrease in R&D expenses was primarily due to a decrease in the Company’s clinical program costs. R&D expenses for the full year 2023 were $43.7 million, compared to $83.3 million for the prior year.

Selling, general, and administrative (SG&A) expenses for the fourth quarter of 2023 were $15.2 million, compared to $23.6 million for the fourth quarter of 2022. The decrease in SG&A expenses was primarily due to decreases in commercialization activities, personnel costs, and medical affairs. SG&A expenses for the full year 2023 were $71.1 million, compared to $100.4 million for the prior year.

The net loss for the fourth quarter of 2023 was $10.9 million, compared to $33.6 million for the fourth quarter of 2022. Net loss for the full year 2023 was $48.0 million, compared to a net loss of $147.6 million for the prior year. The basic and diluted net loss per share for the fourth quarter of 2023 was $(0.21), compared to $(0.73) for the fourth quarter of 2022. The basic and diluted net loss per share for the full year 2023 was $(0.93) compared to $(3.38) for the prior year.

2024 Financial Guidance

G1 today provided full year 2024 financial guidance. The Company expects to generate between $60 million and $70 million in COSELA net revenue in 2024. G1’s product revenue guidance is based on expectations for continued acceleration of sales performance of COSELA in the U.S. Additionally, the Company believes that its current cash runway is sufficient to fund its operations into 2025.

Webcast and Conference Call

G1 will host a webcast and conference call at 8:30 a.m. ET today to provide a corporate and financial update for the fourth quarter and full year ended December 31, 2023.

Please note the following process to access the call via telephone: To register and receive a dial in number and unique PIN to access the live conference call, please follow this link to register online. While not required, it is recommended to join 10 minutes prior to the start of the event. A live and archived webcast will be available on the Events & Presentations page of the Company’s website: www.g1therapeutics.com. The webcast will be archived on the same page for 90 days following the event.

About COSELA (trilaciclib) for Injection

COSELA (trilaciclib) was approved by the U.S. Food and Drug Administration on February 12, 2021.

Indication

COSELA (trilaciclib) is indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer.

Important Safety Information

COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib.

Warnings and precautions include injection-site reactions (including phlebitis and thrombophlebitis), acute drug hypersensitivity reactions, interstitial lung disease (pneumonitis), and embryo-fetal toxicity.

The most common adverse reactions (>10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia.

This information is not comprehensive. Please click here for full Prescribing Information. View Source

To report suspected adverse reactions, contact G1 Therapeutics at 1-800-790-G1TX or call FDA at 1-800-FDA-1088 or visit www.fda.gov/medwatch.

On February 28, 2024 CymaBay Therapeutics, Inc. (NASDAQ: CBAY), a clinical-stage biopharmaceutical company focused on developing therapies for liver and other chronic diseases with high unmet need, reported corporate updates and financial results for the year and fourth quarter ended December 31, 2023 (Press release, CymaBay Therapeutics, FEB 28, 2024, View Source [SID1234640580]).

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"2023 was a seminal year for CymaBay with critical achievements in the development of our investigational therapeutic, seladelpar. The Phase 3 RESPONSE data presented in 2023 and recently published in the New England Journal of Medicine, indicate that seladelpar has the potential to raise the bar in PBC second-line treatment and improve quality of life for people living with this debilitating condition," said Sujal Shah, President and CEO of CymaBay. "Our team moved at speed to submit seladelpar to regulatory agencies and with an updated breakthrough therapy designation were able to secure FDA priority review. These accomplishments were recognized with the recent announcement of the pending acquisition of CymaBay by Gilead. I am incredibly proud of the team and everything that has been achieved in 2023 to help bring seladelpar to people living with PBC, and believe that through Gilead, seladelpar can reach a broad range of people that may benefit in 2024 and beyond."

2023 and Recent Corporate Highlights

Pending Acquisition by Gilead:

On February 11, 2024, CymaBay entered into a definitive agreement with Gilead Sciences, Inc. (Gilead) under which Gilead will acquire CymaBay for $32.50 per share in cash or a total equity value of $4.3 billion. The transaction is anticipated to close during the first quarter of 2024, subject to the receipt of regulatory approvals and the satisfaction of other customary closing conditions.
Regulatory Updates and Launch Readiness:

In February 2024, the U.S. Food and Drug Administration (FDA) accepted a New Drug Application (NDA) for seladelpar, an investigational treatment for the management of primary biliary cholangitis (PBC) including pruritus in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who are inadequate responders or intolerant to ursodeoxycholic acid. The FDA has granted priority review and set a Prescription Drug User Fee Act target action date of August 14, 2024. The agency has notified the company that it is not currently planning to hold an advisory committee meeting to discuss the application.
CymaBay has received validation of its application to the U.K. Medicines Healthcare products Regulatory Agency (MHRA) for seladelpar for the treatment of PBC. Seladelpar has also been submitted to the European Medicines Agency (EMA) and validation of the application is anticipated in H1 2024. Review by both agencies is anticipated to be completed in 2025.
In the U.S., this application was further supported by the Breakthrough Therapy Designation for seladelpar, that was updated by the FDA in October 2023, with clinical results that indicate seladelpar may provide meaningful improvement over existing therapy based on a reduction in alkaline phosphatase (ALP) and improvement in pruritus in patients without cirrhosis or with compensated cirrhosis.
In preparation for the potential launch of seladelpar in the U.S. in 2024, CymaBay hired, trained and deployed a medical affairs team with a range of expertise across PBC, rare disease and liver diseases to drive PBC education. Our pre-commercial launch planning efforts in the U.S. accelerated in the fourth quarter as we built strong commercial strategy, marketing, market access, commercial operations and analytics teams with experience in launching new treatments in rare diseases and competitive therapeutics areas and markets.
Clinical Development:

In mid-2023, CymaBay announced initiation of the IDEAL study, a 52-week, placebo-controlled, randomized, Phase 3 study. The IDEAL study aimed to enroll 75 patients with PBC who have an incomplete response or intolerance to ursodeoxycholic acid (UDCA), with ALP levels greater than the upper limit of normal (ULN) but less than 1.67x ULN, and total bilirubin less than or equal to 2x ULN. To ensure IDEAL is well powered to effectively assess both liver biochemistry and pruritus impact we are now doubling the study size to 150 patients with a 2:1 ratio of patients receiving seladelpar vs. placebo. The primary outcome measure is the ALP composite of normalization and a greater than or equal to 15% decrease in ALP at 52 weeks. A key secondary endpoint is evaluating the change in pruritus Numerical Rating Scale (NRS) at six months in subjects with moderate to severe pruritus at baseline.
Enrollment in the long-term ASSURE study continues. ASSURE is an open-label study of seladelpar in patients with PBC intended to collect additional long-term safety and efficacy data to further support registration. There are now over 300 patients taking seladelpar 10 mg daily, through the study including those from prior studies of seladelpar and patients who have completed RESPONSE.
In 2023, CymaBay initiated AFFIRM, a randomized, placebo-controlled confirmatory study to evaluate the effect of seladelpar 10 mg daily on clinical outcomes in patients with compensated cirrhosis due to PBC. The AFFIRM study is planned to enroll approximately 192 patients with PBC who have compensated cirrhosis (Child-Pugh A or Child-Pugh B) based on prespecified clinical criteria. Patients will be randomly assigned using a 2:1 ratio to seladelpar or placebo for a fixed duration of three years. The primary outcome measure is the time to the first occurrence of clinical events (all-cause death, liver transplant, hospitalization for other serious liver-related events, and progression to Child-Pugh C decompensated cirrhosis). Additional key outcomes include overall survival, liver transplant-free survival, and time to hospitalization for serious liver-related events.
Presentations and Publications:

The pivotal Phase 3 RESPONSE study was presented at The Liver Meeting 2023 of the American Association for the Study of Liver Diseases, in Boston Massachusetts, and later published online in the New England Journal of Medicine in February 2024. The clinical data includes:
RESPONSE was a double-blind, placebo-controlled, global study of one-year duration that randomized 193 PBC patients in a 2:1 ratio to seladelpar 10 mg or placebo, once daily. Eligible patients had an inadequate response or intolerance to ursodeoxycholic acid (UDCA) with serum alkaline phosphatase (ALP) ≥ 1.67× the upper limit of normal (ULN) after at least 12 months of treatment.
The primary endpoint was a composite of ALP and total bilirubin previously accepted by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for registration studies in PBC. The composite endpoint was achieved in 61.7% of patients on seladelpar vs. 20.0% on placebo (p<0.0001).
The key secondary endpoint of ALP normalization occurred in 25% of patients receiving seladelpar vs. 0% for patients on placebo (p<0.0001). The average decrease in ALP for patients on seladelpar was -133.9 U/L vs. -16.9 U/L for patients on placebo (p<0.0001).
The study also measured the impact on patient-reported pruritus (itching), one of the most challenging symptoms experienced by people with PBC, as a key secondary endpoint using the daily numerical rating scale (NRS; 0-10). The pruritus endpoint was met at Month 6 among patients with baseline NRS > 4 reporting decreases of 3.2 points with seladelpar (n=65) vs. 1.7 for patients on placebo (n=20; p<0.005). Notably, these improvements were sustained through Month 12 (p<0.005). A statistically significant reduction in pruritus was also observed at Month 6 and at Month 12 for patients in the intent-to-treat population, which includes all patients irrespective of their NRS score at baseline.
CymaBay published a post-hoc analysis of the Phase 3 ENHANCE study in the open access journal Hepatology, demonstrating the impact of seladelpar on serum interleukin-31 (IL-31) levels and its correlation with pruritus improvement in people with PBC.
Financial Updates:

Held $416.2 million in cash, cash equivalents and investments as of December 31, 2023.

Fourth Quarter and Year Ended December 31, 2023, Financial Results:

Collaboration revenue recognized for the year ended December 31, 2023 was $31.1 million and was associated with the collaboration and license agreement with Kaken Pharmaceutical Co., Ltd. (Kaken) entered into in January 2023, to develop and commercialize seladelpar in Japan. As reported earlier, $31.0 million of this revenue was recognized upon completion of the initial technology transfer to Kaken in the second quarter of 2023. Of the $34.2M upfront payment received from Kaken, $2.7 million remains deferred as of December 31, 2023 and will be recognized upon completion of CymaBay’s ongoing clinical data delivery and CMC development performance obligations.
Research and development expenses for the three months ended December 31, 2023 and 2022 were $22.8 million, and $16.2 million, respectively. Research and development expenses for the years ended December 31, 2023, and 2022 were $80.8 million and $68.0 million, respectively. Research and development expenses for the three months and year ended December 31, 2023 increased compared to the corresponding periods in 2022 driven by higher clinical activities supporting our clinical studies and higher spend supporting our regulatory filings.
General and administrative expenses for the three months ended December 31, 2023 and 2022 were $19.8 million and $7.2 million, respectively. General and administrative expenses for the years ended December 31, 2023 and 2022 were $51.9 million and $25.1 million, respectively. General and administrative expenses for the three months and year ended December 31, 2023 were higher than the corresponding periods in 2022 driven by investments to prepare for potential commercialization of seladelpar in PBC as well as increase in other corporate expenses.
Net loss for the three months ended December 31, 2023 and 2022 was $41.9 million and $26.6 million, or ($0.35) and ($0.30) per share, respectively. Net loss for the year ended December 31, 2023 and 2022 was $105.4 million and $106.0 million, or ($0.99) and ($1.21) per share, respectively. Net loss for the three months ended December 31, 2023 was higher than the three months ended December 31, 2022 primarily due to higher operating expenses. Net loss in the year ended December 31, 2023 was slightly lower than the corresponding period in 2022 due primarily to $31.0 million of collaboration revenue related to the Kaken upfront payment during the second quarter of 2023 and higher interest income earned on our investments and other income due to refundable tax credits, offset in part by an increase in operating expenses and interest expense from the Abingworth development financing arrangement.

On February 28, 2024 Crinetics Pharmaceuticals, a clinical-stage pharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for rare endocrine diseases and endocrine-related tumors, reported that it has agreed to sell 8,333,334 shares of its common stock at a price of $42.00 per share to a select group of institutional and accredited healthcare specialist investors in an oversubscribed private placement (Press release, Crinetics Pharmaceuticals, FEB 28, 2024, View Source [SID1234640579]). Crinetics anticipates the gross proceeds from the private placement to be approximately $350 million, before deducting any offering-related expenses. The private placement is expected to close on or about March 1, 2024, subject to the satisfaction of customary closing conditions.

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The financing includes participation from new and existing institutional investors, including Adage Capital Partners L.P., Driehaus Capital Management, EcoR1 Capital, First Light Asset Management, GordonMD Global Investments LP, Invus, Janus Henderson Investors, Paradigm BioCapital, Perceptive Advisors, Rock Springs Capital, as well as multiple leading mutual funds.

Leerink Partners, Piper Sandler, Baird, Citizens JMP, H.C. Wainwright & Co., and LifeSci Capital are acting as placement agents to the Company in connection with the private placement.

Crinetics intends to use the net proceeds from the private placement to fund research and development of its clinical-stage product candidates, other research programs, working capital and general corporate purposes.

The offer and sale of the securities to be sold in the private placement have not been registered under the Securities Act of 1933, as amended (the "Securities Act"), or any state or other applicable jurisdiction’s securities laws, and such securities may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements of the Securities Act and applicable state or other jurisdictions’ securities laws. Crinetics has agreed to file a registration statement with the U.S. Securities and Exchange Commission (the "SEC") registering the resale of the shares of common stock issued in the private placement no later than the 40th day after the pricing of the private placement.

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

On February 28, 2024 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with genetically defined cancers, reported that its Chief Executive Officer, Mark A. Velleca, M.D., Ph.D., will participate in a panel discussion on lung cancer at the TD Cowen 44th Annual Health Care Conference on Wednesday, March 6, 2024, at 9:10 a.m. ET in Boston, MA (Press release, Black Diamond Therapeutics, FEB 28, 2024, View Source [SID1234640578]).

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A live webcast of the panel can be accessed by visiting the investor relations section of the Company’s website at: www.blackdiamondtherapeutics.com. A replay of the webcast will also be available and archived for 90 days following the event.