On February 28, 2024 Inhibikase Therapeutics, Inc. (Nasdaq: IKT) ("Inhibikase" or "Company"), a clinical-stage pharmaceutical company developing protein kinase inhibitor therapeutics to modify the course of Parkinson’s disease, Parkinson’s-related disorders and other diseases of the Abelson Tyrosine Kinases, reported preliminary outcomes of the Company’s discussion with the U.S. Food and Drug Administration (FDA) on the path to approval of IkT-001Pro in blood and stomach cancers, the Company’s prodrug of the anticancer agent imatinib mesylate (Press release, Inhibikase Therapeutics, FEB 28, 2024, View Source [SID1234640585]).

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"With the full meeting minutes from the FDA Review Team in hand, we are confident in our approach as we develop the NDA for IkT-001Pro," said Dr. Milton Werner, President and Chief Executive Officer of Inhibikase. "Of note, we may not need to complete a formal risk analysis of the possibility of medication errors following discussion of alternative dosage forms with the FDA, but we will have to provide justification for the selected dosage forms to be proposed in the NDA. Further, we are not restricted from use in children nor restricted to just blood cancer-related approved indications. This opens-up the opportunity to seek all 11 approved indications for IkT-001Pro that were previously approved for imatinib mesylate. We are pleased with the discussions we’ve had so far with the FDA and look forward to the work ahead of us needed for the NDA submission."

On February 12, 2024, the FDA Review Team from the Division of Hematologic Malignancies issued final meeting minutes from the pre-NDA video conference that took place January 19, 2024. In the minutes, the FDA noted that it may not be necessary to conduct a formal use-related risk analysis of medication errors due to the Company proposing dosage forms that would not overlap with those of imatinib mesylate. In the NDA package, the Company will have to justify why its alternate dosage forms could overcome the risk of dosing errors by physicians and patients. Following the discussion with the Review Team about possible differences in the way IkT-001Pro and imatinib mesylate are absorbed in the gut, the FDA agreed with the Company’s assertion that a pre-clinical analysis of gut absorption should be performed to determine whether a food effect clinical study is warranted, since the Company’s clinical measures were all performed using an FDA-approved meal prior to taking IkT-001Pro or imatinib mesylate. While the Company will have to supply data and/or rationale for use of IkT-001Pro in any indication for which imatinib mesylate is approved, use in children will need to be accompanied by a statutory planning document related to dose adjustments and use in children of different ages and/or weights. This planning document is required for any product in which use in children is proposed. All other elements of the pre-NDA meeting remain unchanged from those reported on February 7, 2024.

The Company continues to explore additional indications for which imatinib delivered by IkT-001Pro could be useful and has an upcoming meeting with the FDA to discuss cardiopulmonary applications of IkT-001Pro in April, 2024.

About IkT-001Pro
IkT-001Pro is a prodrug formulation of imatinib mesylate and has been developed to improve the safety of the first FDA-approved Abelson (Abl) kinase inhibitor, imatinib (marketed as Gleevec). Imatinib is commonly taken for hematological and gastrointestinal cancers that arise from Abl kinase mutations found in the bone marrow or for gastrointestinal cancers that arise from c-Kit and/or PDGFRa/b mutations in the stomach; c-Kit, PDGFRa/b and Abl are all members of the Abelson Tyrosine Kinase protein family. IkT-001Pro has the potential to be a safer alternative for patients and may improve the number of patients that reach and sustain major and/or complete cytogenetic responses in Stable-Phase Chronic Myelogenous Leukemia ("Stable-Phase CML") and/or reduce the relapse rate for these patients. In preclinical studies, IkT-001Pro was shown to be as much as 3.4 times safer than imatinib in primates, reducing burdensome gastrointestinal side effects that occur following oral administration. Imatinib delivered as IkT-001Pro was granted Orphan Drug Designation for Stable-Phase CML in September, 2018.

On February 28, 2024 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, reported its financial results for the fourth quarter and year ended December 31, 2023 and provided a business update (Filing, 3 mnth, DEC 31, Immunocore, 2024, FEB 28, 2024, View Source [SID1234640584]).

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"In the last 5 years, Immunocore has transformed from a research organization to a revenue-generating, sustainable company," said Bahija Jallal, CEO of Immunocore. "We look forward to the next 5 years, when we maximize the potential of KIMMTRAK, expect to launch our PRAME ImmTAC therapy, and advance our clinical candidates across oncology, infectious diseases and autoimmune diseases."

"Throughout the last year, we expanded the reach of KIMMTRAK in metastatic uveal melanoma with additional approvals, launches, and sales growth across all territories," said Ralph Torbay, Head of Commercial. "We believe KIMMTRAK, the world’s first approved TCR therapy, could benefit thousands more patients and look forward to broadening indications with ongoing late-stage clinical trials in cutaneous and adjuvant uveal melanoma."

Full Year and Fourth Quarter 2023 Highlights (including post-period)

Financial Results

Total net product revenue (or "net sales) arising from the sales of KIMMTRAK (tebentafusp) was $67.6 million in the fourth quarter of 2023, of which $49.1 million was generated in the United States, $18.3 million in Europe and $0.2 million in international regions. For the year ended December 31, 2023, the Company generated net sales from the sale of KIMMTRAK in the amount of $238.7 million, of which $169.8 million was in the United States, $67.6 million in Europe and $1.3 million in international regions.

Research & development expenses for the year 2023 were $163.5 million, compared to $101.9 million for the year 2022. Selling, general and administrative (SG&A) expenses for the year 2023 were $144.5 million, compared to $123.1 million for the year 2022.

Net loss for the fourth quarter of 2023 was $19.7 million compared to a net loss of $30.0 million in the same period in 2022, and full year net loss for 2023 was $55.3 million compared to a full year net loss of $52.5 million in 2022.

The fourth quarter basic and diluted loss per share was $0.40, compared to $0.64 for the fourth quarter of 2022. Basic and diluted loss per share for 2023 was $1.13, compared to $1.15 for 2022.

Cash and cash equivalents at December 31, 2023 were $442.6 million. In February 2024, the Company raised net cash proceeds of $389.3 million from an offering of convertible notes with a six-year term and 2.50% interest rate (Convertible Notes).

KIMMTRAK expansion strategy

KIMMTRAK (tebentafusp-tebn) for metastatic uveal melanoma

Since the start of the 2024, KIMMTRAK has been launched in two additional countries (Australia and Canada), for a total of 12 launched and 38 approved countries. KIMMTRAK continues to be the standard of care for HLA-A02+ patients with metastatic uveal melanoma (mUM) in all of the countries in which it has been launched. In 2024, the Company plans to reach more patients in the United States, Europe and globally, as it continues to drive global launches and focuses on supporting early patient identification and treatment.

KIMMTRAK Phase 2/3 clinical trial in 2L+ advanced cutaneous melanoma

The Company also continues to enroll patients into a Phase 2/3 clinical trial (TEBE-AM) to investigate the potential of KIMMTRAK in 2L+ advanced cutaneous melanoma. Topline data from the Phase 2 portion of the trial is expected to be available by the fourth quarter of 2024.

KIMMTRAK Phase 3 clinical trial in adjuvant uveal (or ocular) melanoma

In 2023, the Company signed an agreement for a European Organisation for Research and Treatment of Cancer (EORTC)-sponsored trial to study KIMMTRAK as adjuvant therapy for uveal (or ocular) melanoma (ATOM). The Company anticipates that the EORTC will randomize the first patient in the second half of 2024.

PRAME franchise

PRISM-MEL301 – First PRAME Phase 3 clinical trial with IMC-F106C in first-line advanced cutaneous melanoma

In February 2024, the Company entered into a clinical trial collaboration and supply agreement with Bristol Myers Squibb (NYSE:BMY) to investigate Immunocore’s ImmTAC bispecific TCR candidate targeting PRAME HLA-A02, IMC-F106C, in combination with Bristol Myers Squibb’s nivolumab, in first-line advanced cutaneous melanoma. Under the terms of the collaboration, Immunocore will sponsor and fund the registrational Phase 3 clinical trial of IMC-F106C in combination with nivolumab in first-line advanced cutaneous melanoma (PRISM-MEL-301), and Bristol Myers Squibb will provide nivolumab.

In August 2023, the Company announced plans to start a registrational Phase 3 clinical trial with IMC-F106C in first-line advanced cutaneous melanoma (CM). The Company decided to advance IMC-F106C into a Phase 3 first-line CM clinical trial in combination with nivolumab with a primary endpoint of progression-free survival (PFS), based on the Company’s analysis of the ongoing Phase 1 data in previously treated CM which demonstrated monotherapy clinical activity including partial responses (PR), durable tumor reduction, disease control (PR and SD), PFS and circulating tumor DNA (ctDNA) reduction (consistent with prior reported data for IMC-F106C and tebentafusp). Additional rationale includes safety in combination with checkpoints (from the ongoing Phase 1 data and prior experience with tebentafusp) and evidence from across the platform for increased clinical activity in earlier line patients compared to later line. As such, PRISM-MEL-301, the first PRAME Phase 3 clinical trial with IMC-F106C, will randomize patients with HLA-A*02:01-positive, first-line advanced CM to IMC-F106C + nivolumab versus a control arm of either nivolumab or nivolumab + relatlimab, depending on the country where the patient is enrolled. The Company plans to randomize the first patient in this trial in the first quarter of 2024.

Phase 1/2 clinical trial of IMC-F106C targeting PRAME-A02 in multiple solid tumors

In addition to progressing IMC-F106C into a registrational trial in cutaneous melanoma, the Company is continuing to enroll patients in the monotherapy and combination arms of the Phase 1/2 clinical trial across multiple tumor types, including expansion arms for patients with advanced ovarian, non-small cell lung, and endometrial carcinoma. The initial data from the Phase 1 clinical trial of IMC-F106C, the first PRAME x CD3 ImmTAC bispecific protein, was presented at the 2022 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in September 2022. Durable Response Evaluation Criteria in Solid Tumors (RECIST) responses and reduction in ctDNA were observed across multiple solid tumors. In August 2023, the Company provided an updated analysis of the original 18 melanoma patients (initially presented at ESMO (Free ESMO Whitepaper) in September 2022), which continued to show promising durability of the clinical activity (range of duration of partial response from 6 months to 17 months). The Company expects to report clinical data from the ongoing monotherapy and combination cohorts throughout 2024 including cutaneous melanoma (expected in Q2 2024), ovarian (expected by Q3 2024), and non-small cell lung carcinoma (expected by Q4 2024).

IMC-P115C (PRAME HLA-A02 Half-Life Extended) & IMC-T119C (PRAME HLA-A24)

The Company is expanding the PRAME franchise with two new PRAME ImmTAC candidates, IMC-P115C (PRAME HLA-A02 HLE) and IMC-T119C (PRAME HLA-A24) for solid tumors, which are both on track for investigational new drug (IND) or clinical trial application (CTA) submissions for IMC-P115C in the middle of 2024 and the fourth quarter of 2024 for IMC-T119C.

IMC-R117C (PIWIL1) for colorectal and other gastrointestinal cancers

The Company has leveraged its proprietary peptide (ImmSPECT) database to validate a novel target, PIWIL1. PIWIL1 is believed to play a role in tumor progression and is expressed across a range of tumors, including colorectal which is historically insensitive to immune checkpoints, as well as other gastrointestinal cancers. PIWIL1 is also reported to be a negative prognostic marker and the Company believes IMC-R117C is the first PIWIL1-targeted immunotherapy. The Company submitted a CTA to regulatory authorities in December 2023, and expects the trial to start in the second half of 2024.

Enrolling ImmTAV candidates for a functional cure in infectious diseases

The Company continues to enroll people living with HIV in the multiple ascending dose (MAD) part of a Phase 1 clinical trial with IMC-M113V, to identify a safe and tolerable dosing schedule. This trial will also test whether IMC-M113V could lead to reduction in the viral reservoir and, after stopping all therapies (antiretroviral therapies and IMC-M113V), delay or prevent HIV rebound (known as functional cure). The MAD part of the trial will enroll up to 28 participants. The Company expects to present a data update from the Phase 1 clinical trial in the second half of 2024.

In 2023, the Company amended the design of the ongoing Phase 1 clinical trial with IMC-I109V for people living with HBV to include HBV-positive hepatocellular carcinoma. The Company continues to enroll patients into the single ascending dose portion of the trial in 2024.

Tissue-specific down modulation of the immune system for autoimmune diseases

The Company is expanding its platform into autoimmune diseases with two first-in-class new bispecific candidates entering the Company’s pipeline. The key differentiator of the ImmTAAI platform is tissue-specific down modulation of the immune system. When tethered to the tissue of interest, the new candidates supress pathogenic T cells via PD1 receptor agonism.

The first candidate, IMC-S118AI (PPIxPD1), is targeted specifically to pancreatic beta cells and is intended for disease-modifying treatment in type 1 diabetes. IMC-S118AI recognizes a peptide from pre-proinsulin presented by HLA-A02 on beta cells coupled with a PD1 agonist effector arm. IMC-S118AI is advancing towards GMP manufacturing in 2024.

The second target is present in the skin and intended to treat inflammatory dermatological diseases. The candidate is an antigen presenting cell (APC) tethered ImmTAAI and is not HLA restricted (e.g. universal for all populations).

Financial Results

Basic and diluted loss per share was $0.40 and $1.13 for the quarter and year ended December 31, 2023, respectively, as compared to a basic and diluted loss per share of $0.64 and $1.15, respectively, for the same periods in 2022. Net loss for the quarter and year ended December 31, 2023, was $19.7 million and $55.3 million, respectively, as compared to $30.0 million and $52.5 million, respectively, for the same periods in 2022.

For the fourth quarter and year ended December 31, 2023, we generated net sales of $67.6 million and $238.7 million, respectively, due to the sale of KIMMTRAK and tebentafusp, of which $49.1 million and $169.8 million, respectively was in the United States, $18.3 million and $67.6 million, respectively, was in Europe, and $0.2 million and $1.3 million, respectively, was in the international regions. The increase in net sales was due primarily to increased volume in the United States and global country expansion, as we continued our commercialization efforts.

For the fourth quarter and year ended December 31, 2023, our research and development (R&D) expenses were $45.6 million and $163.5 million, respectively as compared to $31.1 million and $101.9 million for the quarter and year ended December 31, 2022. These increases were driven by expenses incurred for our PRAME programs, increases in headcount-related expenses as a result of higher number of employees and associated staff costs, increases related to consumables and facilities costs, and decreased R&D tax credits due to us no longer qualifying as a ‘small and medium enterprise’ (SME) under the UK R&D tax regulations. The Company expects R&D expenses to increase in future periods as the Company advances its trials and further develops clinical and preclinical pipeline candidates.

For the quarter and year ended December 31, 2023, our SG&A expenses were $41.4 million and $144.5 million, respectively, compared to $35.4 million and $123.1 million for the quarter and year ended December 31, 2022. These increases were related to an increase in headcount costs, higher selling and distribution costs following regulatory approval of KIMMTRAK, and costs associated with expansion as a growing publicly listed and commercial company.

Cash and cash equivalents were $442.6 million as of December 31, 2023, as compared to $402.5 million as of December 31, 2022. In February 2024, the Company raised net cash proceeds of $389.3 million from a Convertible Notes offering with a six-year term and 2.50% interest rate. The Company plans to use $50 million from the net proceeds to repay its existing Pharmakon loan by the end of 2024. The Company estimates Pro Forma for the net cash proceeds from the Convertible Notes offering in February 2024, and the Pharmakon loan repayment, its cash and cash equivalents at year-end 2023, were approximately $782 million.

As of December 31, 2023, the Company no longer qualified as a foreign private issuer for U.S. publicly company reporting purposes. Effective January 1, 2024, it now files periodic reports on U.S. domestic filer forms with the Securities and Exchange Commission (SEC) and comply with other rules as required, including but not limited to presenting its financial results in press releases and Annual Report on Form 10-K in accordance with U.S. GAAP, with such change being applied retrospectively. See the Company’s Annual Report on Form 10-K filed today with the SEC for more information.

On February 28, 2024 HUTCHMED (China) Limited, the innovative, commercial-stage biopharmaceutical company, reported its financial results for the year ended December 31, 2023 and provides updates on key clinical and commercial developments (Filing, 3 mnth, DEC 31, Hutchison China MediTech, 2024, FEB 28, 2024, View Source [SID1234640583]). HUTCHMED to host results call and webcasts today at 7:30 a.m. EST / 12:30 p.m. GMT / 8:30 p.m. HKT in English, and at 8:30 a.m. HKT in Chinese (Putonghua) on Thursday, February 29, 2024.

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All amounts are expressed in U.S. dollars unless otherwise stated.

Strategic: global vision, commitment to patients and path to self-sustainability

· Executed our global vision of bringing our innovative medicines worldwide, as demonstrated through the Takeda1 partnership which brought $435 million in upfront and milestone payments plus manufacturing income and royalties on net sales, setting a strategic example for the rest of our pipeline.

· On track to be self-sustaining with a disciplined approach to leveraging our R&D2 expertise and creating value through licensing and commercialization.

Pipeline: fruquintinib global and China expansion, sovleplenib China NDA3 review, savolitinib NSCLC4 enrolled

· Fruquintinib U.S. FDA5 approval three weeks ahead of PDUFA6 date for third-line CRC7, leading to a swift launch by Takeda, inclusion in NCCN8 guidelines and U.S. in-market sales9 of $15.1 million. Global regulatory progress with MAA10 filing to the EMA11 validated in June 2023 and NDA submitted to PMDA12 in September 2023.

· Fruquintinib NDA for second-line gastric cancer accepted for review in China. Registrations studies in China for 2L EMC13 and 2L RCC14 completed enrollment during 2023 for fruquintinib in combination with sintilimab, expecting NDA filing to the NMPA15 for EMC in early 2024 and topline results for RCC by end of 2024.

· NDA for sovleplenib, a novel Syk16 inhibitor, for primary ITP17 accepted and granted priority review in China, supported by data from Phase III trial (ESLIM-01), meeting all endpoints.

· SAVANNAH, the pivotal global Phase II trial for savolitinib in NSCLC, completed enrollment, to be followed by potential NDA filing to the U.S. FDA by AstraZeneca18 around the end of 2024.

Outlook and financial: expecting strong product revenue growth and reduced expenses; substantial cash

· Total revenue up 97% (102% at CER19) to $838.0 million for 2023, with Oncology/Immunology consolidated revenue up 223% (228% at CER) to $528.6 million at high end of guidance, including recognition of $280 million of the upfront payment from Takeda. Net income attributable to HUTCHMED of $100.8 million.

· 2024 Oncology/Immunology consolidated revenue guidance of $300 million to $400 million, driven by 30% to 50% growth target in marketed product sales and royalties.

· R&D expenses focused in line with strategy targeting key projects.

· Strengthened cash balance, with $886.3 million at year end (2022: $631.0m), ensures HUTCHMED is well placed to deliver on its objective of becoming a self-sustaining business.

2023 FULL YEAR RESULTS & BUSINESS UPDATES

Mr Simon To, Executive Chairman of HUTCHMED, said, "We have made significant progress throughout 2023. We executed against our commitment to bring our innovative medicines to patients worldwide with the U.S. FDA approval of FRUZAQLA in November 2023, while remaining dedicated to becoming a self-sustaining business. The Takeda partnership, which is one of the biggest small-molecule overseas licensing deals in the history of China biotech, strengthened our cash position by $435 million. Takeda delivered a successful U.S. launch within 48 hours of approval, and has subsequently seen strong early patient uptake."

"We will continue to deliver on our strategy in 2024. We will stay focused on our target of becoming sustainable through our balanced strategy of growing sales of our novel medicines in China, and advancing our medicines overseas with our partners. This, when combined with our other goals on pipeline progression and further business development, means that while the global macroeconomic environment remains uncertain. HUTCHMED is positioned to thrive and continue to deliver innovative medicines to ever more patients around the world."

Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, said, "HUTCHMED delivered impressive financial results in 2023, with revenue up 97% to $838 million. This, alongside our significantly strengthened cash balance of $886 million, will enable us to continue advancing our pipeline and successfully executing our strategy."

"2023 was an important year for HUTCHMED, particularly for fruquintinib, for which we filed market authorization applications in the U.S., EU and Japan, based on the successful FRESCO-2 study. Following the U.S. FDA approval for third-line patients with advanced CRC, we continue to work together with Takeda continue to pursue additional launches in new markets worldwide. In China, we also filed an NDA for second-line gastric cancer based on the FRUTIGA study."

"Another milestone was the successful ESLIM-01 registration study in China in ITP patients for sovleplenib, our first potential novel medicine in immunological diseases. The NDA was accepted and granted priority review by the NMPA in January 2024. There are over 250,000 new and existing adult ITP patients in China.20 The treatment options are limited to steroids and TPO/TPO-RAs21, representing an unmet medical need that sovleplenib could help address, with its new mechanism of action and favorable safety profile. Syk inhibition has the potential to target other major diseases such as rheumatoid arthritis. We are also planning to initiate clinical development of sovleplenib outside China in 2024."

"For savolitinib, we completed the confirmatory trial in NSCLC patients with MET22 exon 14 skipping alterations. An NDA submission is expected in the first quarter of 2024, with potential to expand the label indication to include first-line patients in China. Outside China, we will continue our work with AstraZeneca on the pivotal global savolitinib lung cancer trial SAVANNAH, which, subject to favorable data, can support a filing to the U.S. FDA for approval. This study completed enrollment with a potential NDA submission towards the end of 2024 in EGFR23 mutant NSCLC patients who progressed on TAGRISSO treatment, which received U.S. FDA Fast Track designation in January 2023. We believe the convenient dosing, targeted efficacy and safety profile of savolitinib as an oral medicine in combination with TAGRISSO, the leading oral third-generation EGFR TKI24, should position it well in a competitive market and address the unmet needs of MET+ NSCLC patients."

"Our China commercialization efforts progressed well, as we successfully renewed NRDL25 coverage for both fruquintinib and surufatinib without further price reduction. Their in-market sales saw strong growth in 2023. Over the next two years, we plan to continue growth in China through expanded indications and the launch of new products together with revenue from FRUZAQLA overseas commercialization."

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.