On December 10, 2024 IMUNON, Inc. (NASDAQ: IMNN), a clinical-stage company in late-stage development with its DNA-mediated immunotherapy, reported additional clinical data from ongoing analyses of results from the Company’s Phase 2 OVATION 2 Study of IMNN-001, its investigational interleukin-12 (IL-12) immunotherapy for the treatment of advanced ovarian cancer based on its proprietary TheraPlas technology (Press release, IMUNON, DEC 10, 2024, View Source [SID1234648985]). The updated results, based on an additional seven months of patient monitoring, show the hazard ratio (HR) decreased from 0.74 to 0.69, with an increase in median overall survival (OS) from 11.1 to 13 months following treatment with IMNN-001 plus standard-of-care (SoC) neoadjuvant and adjuvant chemotherapy (NACT) versus SoC alone. More than one-third of patients in the trial survived more than 36 months from the point of study enrollment, with 62% of those surviving patients from the IMNN-001 treatment arm and 38% from the SoC arm. Over 10% of trial participants have reached 48 months or beyond.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"These results indicate that OS benefits are being maintained in the population of patients treated with IMNN-001, providing strong additional validation of the potential for our novel IL-12 immunotherapy to represent a historic advance in the treatment of ovarian cancer," said Stacy Lindborg, Ph.D., president and chief executive officer of IMUNON. "We understand the significant challenges that ovarian cancer presents to women and their families, especially women with advanced late-stage disease who are newly diagnosed, and that there is a desperate need for new treatments that can make a meaningful difference. We remain on track to initiate a Phase 3 pivotal clinical trial for IMNN-001 in advanced ovarian cancer in the first quarter of 2025 and look forward to updating on our progress."

The OVATION 2 Study included a total of 112 patients with newly diagnosed advanced ovarian cancer (intent-to-treat population). Study participants were randomized 1:1 to evaluate the safety and efficacy of IMNN-001 (100 mg/m2 administered intraperitoneally weekly) plus NACT of paclitaxel and carboplatin compared to SoC NACT alone. Initial results from the OVATION 2 Study were reported in July 2024 and results were recently presented in a late-breaking session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting in November 2024.

"While most research in ovarian cancer in recent years has focused on maintenance therapies for patients who have already responded to chemotherapy, the fact that we are seeing these positive results maintained in a population of newly diagnosed patients with advanced stages of disease requiring neoadjuvant chemotherapy is unprecedented and especially encouraging," said Premal H. Thaker, M.D., Interim Chief of Gynecologic Oncology, David & Lynn Mutch Distinguished Professor of Obstetrics & Gynecology, Director of Gynecologic Oncology Clinical Research at Washington University School of Medicine, and the OVATION 2 Study Chair. "As the first immunotherapy to achieve clinically effective progression-free and overall survival in ovarian cancer in conjunction with chemotherapy, we are especially excited to advance this promising program to a pivotal Phase 3 clinical trial."

About the Phase 2 OVATION 2 Study

OVATION 2 evaluated the dosing, safety, efficacy and biological activity of intraperitoneal administration of IMNN-001 in combination with neoadjuvant and adjuvant chemotherapy (NACT) of paclitaxel and carboplatin in patients newly diagnosed with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. Treatment in the neoadjuvant period is designed to shrink the tumors as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT, patients undergo interval debulking surgery, followed by three additional cycles of adjuvant chemotherapy to treat any residual tumor. This open-label study enrolled 112 patients who were randomized 1:1 and evaluated for safety and efficacy to compare NACT plus IMNN-001 versus standard-of-care NACT. In accordance with the study protocol, patients randomized to the IMNN-001 treatment arm could receive up to 17 weekly doses of 100 mg/m2 in addition to NACT. As a Phase 2 study, OVATION 2 was not powered for statistical significance. Additional endpoints included objective response rate, chemotherapy response score and surgical response.

About IMNN-001 Immunotherapy

Designed using IMUNON’s proprietary TheraPlas platform technology, IMNN-001 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anticancer immunity acting through the induction of T-lymphocyte and natural killer cell proliferation. IMUNON previously reported positive safety and encouraging Phase 1 results with IMNN-001 administered as monotherapy or as combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer and completed a Phase 1b dose-escalation trial (the OVATION 1 Study) of IMNN-001 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer.

About Epithelial Ovarian Cancer

Epithelial ovarian cancer is the sixth deadliest malignancy among women in the U.S. There are approximately 20,000 new cases of ovarian cancer every year and approximately 70% are diagnosed in advanced Stage III/IV. Epithelial ovarian cancer is characterized by dissemination of tumors in the peritoneal cavity with a high risk of recurrence (75%, Stage III/IV) after surgery and chemotherapy. Since the five-year survival rates of patients with Stage III/IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate, but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for a regional approach to immune modulation.

On December 10, 2024 ImmunityBio, Inc. (NASDAQ: IBRX), a leading immunotherapy company, reported that it intends to offer and sell, subject to market and other conditions, shares of its common stock in an underwritten public offering (Press release, ImmunityBio, DEC 10, 2024, View Source [SID1234648984]). In addition, ImmunityBio expects to grant the underwriters a 30-day option to purchase up to an additional 15% of the shares of common stock offered in the offering at the public offering price, less underwriting discounts and commissions. ImmunityBio currently intends to use the net proceeds from this offering to progress its continued commercialization of ANKTIVA for treatment of BCG-unresponsive non-muscle invasive bladder cancer ("NMIBC") with carcinoma in situ ("CIS") with or without papillary tumors, to fund its trials in BCG-naïve NMIBC and non-small cell lung cancer ("NSCLC"), toward further research and development, for working capital needs, and for other general corporate purposes. All of the shares are being offered by ImmunityBio. There can be no assurance as to whether or when the offering may be completed, or the actual size or terms of the offering.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Jefferies and Piper Sandler are acting as joint book-running managers and representatives of the underwriters for the offering. BTIG and H.C. Wainwright & Co. are acting as co-lead managers for the offering.

A shelf registration statement on Form S-3ASR relating to the common stock offered in the public offering described above was filed with the Securities and Exchange Commission ("SEC") on April 17, 2024 and became automatically effective on April 17, 2024. The proposed offering is being made only by means of a prospectus supplement and accompanying prospectus that form a part of the registration statement. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus supplement and accompanying prospectus relating to the offering, when available, may also be obtained from Jefferies LLC, by mail at Attn: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, New York 10022, by telephone at (877) 821-7388 or by email at [email protected], or Piper Sandler & Co. by mail at Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402 or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy the securities being offered, nor shall there be any sale of the securities being offered in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction. The offering may be made only by means of a prospectus supplement and accompanying prospectus.

On December 10, 2024 Immix Biopharma, Inc. ("ImmixBio", "Company", "We" or "Us" or "IMMX"), a clinical-stage biopharmaceutical company developing cell therapies for AL Amyloidosis and select immune-mediated diseases, reported that new NXC-201 NEXICART-1 clinical data in relapsed/refractory AL Amyloidosis has been presented at 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held in San Diego, California (Press release, Immix Biopharma, DEC 10, 2024, View Source [SID1234648983]). The updated results include follow-up and clinical data from 3 new NEXICART-1 patients.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are encouraged by the updated NXC-201 results being presented by our academic collaborators at ASH (Free ASH Whitepaper) 2024. We believe the high percentage of complete responders, combined with the consistent, attractive tolerability profile is critically important in relapsed/refractory AL Amyloidosis. This expanded NXC-201 dataset continues to bolster our leadership in relapsed/refractory AL Amyloidosis, where no drugs are FDA approved today," said Ilya Rachman, M.D., Ph.D., Chief Executive Officer of Immix Biopharma. Gabriel Morris, Chief Financial Officer of Immix Biopharma, added, "We are looking forward to bringing this promising therapy to U.S. relapsed/refractory AL Amyloidosis patients."

At the NXC-201 ASH (Free ASH Whitepaper) 2024 oral presentation, data were presented from 16 relapsed/refractory AL amyloidosis patients (including 3 new patients) in the ongoing Phase 1b/2 NEXICART-1 study, with median 4 lines of therapy prior to NXC-201. Patients were infused with CAR+T cells at doses of 150 x 106 (n=1), 450 x 106 (n=2), and 800 x 106 (n=13).

Patient characteristics:

81% (13/16) had cardiac involvement
38% (6/16) had New York Heart Association (NYHA) stage 3 or 4 heart failure (3 stage 4, 3 stage 3)
31% (5/16) had Mayo stage 3 (1 stage 3b, 4 stage 3a) AL amyloidosis disease
44% (7/16) had t(11;14) translocation
Relapsed/refractory to a median 4 lines of prior therapy (range: 3-10)
Safety and efficacy data:

Overall response rate of 94% (15/16)
Complete response rate of 75% (12/16) (9 out of 16 were MRD- 10-5)
Organ response rate of 62% (8/13 evaluable)
Best responder had a duration of response of 31.5 months as of December 9, 2024, with complete response ongoing
There were no immune effector cell-associated neurotoxicity syndrome (ICANS) events
Median CRS duration was 2 days (range: 1-5):
No grade 4 cytokine release syndrome (CRS) events
2 experienced no CRS; 3 experienced grade 1 CRS; 8 Experienced grade 2 CRS; 3 experienced grade 3 CRS
The NXC-201 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting oral presentation video can be accessed on the ASH (Free ASH Whitepaper) website: View Source

The NXC-201 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting oral presentation can be accessed on the ImmixBio corporate website at this link: View Source

ASH Presentation Details (CAR-T NXC-201 in relapsed/refractory AL Amyloidosis).

Event 66th ASH (Free ASH Whitepaper) Annual Meeting and Exposition, San Diego, CA
Title "Efficacy and Safety of Anti-BCMA Chimeric Antigen Receptor T-Cell (CART) for the Treatment of Relapsed and Refractory AL Amyloidosis"
Presentation
Date/Time (Pacific Time)
Publication #894
Session Date: Monday, December 9, 2024
Session Name: 652. MGUS, Amyloidosis, and Other Non-Myeloma Plasma Cell Dyscrasias: Clinical and Epidemiological: Ignored no Longer-Progress in AL Amyloidosis
Session Time: 2:45 PM-4:15 PM
Presentation Time: 4:00PM PT
About NEXICART-1
NEXICART-1 (NCT04720313) is an open-label, ex-U.S. Phase 1b/2 clinical trial of NXC-201 (formerly HBI0101) in patients with relapsed/refractory multiple myeloma and relapsed/refractory AL amyloidosis (including AL Amyloidosis patients with impaired cardiac function and including AL Amyloidosis patients exposed to prior BCMA-targeted therapy). The primary objective of the study is to characterize the safety and efficacy of NXC-201. NEXICART-1 clinical results are available at View Source .

About NEXICART-2
NEXICART-2 (NCT06097832) is an open-label, single-arm, multi-site U.S. Phase 1b/2 dose expansion clinical trial of CAR-T NXC-201 in relapsed/refractory AL Amyloidosis. NEXICART-2 is expected to enroll 40 patients with adequate cardiac function who have not been exposed to prior BCMA-targeted therapy. The study is designed with a standard 6 patient safety-run in to evaluate two doses (three patients each at 150 million CAR+T cells and 450 million CAR+T cells) (both dose levels were evaluated in the NEXICART-1 study and have produced complete responses in relapsed/refractory AL Amyloidosis patients). The study aims to evaluate the safety and efficacy of NXC-201. Primary endpoints are complete response rate and overall response rate, according to consensus recommendations (Palladini et al. 2012).

About NXC-201
NXC-201 is a sterically-optimized BCMA-targeted chimeric antigen receptor T (CAR-T) cell therapy. Initial data from Phase 1b/2 ex-U.S. study NEXICART-1 has demonstrated high complete response rates and no neurotoxicity of any kind in AL Amyloidosis.

NXC-201 is being studied in a comprehensive clinical development program for the treatment of patients with relapsed/refractory AL amyloidosis in the U.S., with the potential to expand into select immune-mediated diseases. The NXC-201 NEXICART-2 (NCT06097832) U.S. clinical trial builds on a robust clinical dataset. NXC-201 has been awarded Orphan Drug Designation (ODD) in AL Amyloidosis by the US FDA and in the EU by the EMA.

About AL Amyloidosis
AL amyloidosis is caused by abnormal plasma cells in the bone marrow, which produce misfolded amyloid proteins that build-up in the heart, kidney, liver, and other organs. This build-up causes progressive and widespread damage to multiple organs, including heart failure, and leads to high mortality rates.

The U.S. observed prevalence of relapsed/refractory AL Amyloidosis is estimated to be growing at 12% per year according to Staron, et al Blood Cancer Journal, to approximately 33,277 patients in 2024.

The Amyloidosis market was $3.6 billion in 2017, and is expected to reach $6 billion in 2025, according to Grand View Research.

On December 10, 2024 Halia Therapeutics, a biopharmaceutical company at the forefront of developing treatments for chronic inflammation and related disorders, reported promising topline data resulting in the advancement to the second stage of its Phase 2 clinical trial evaluating HT-6184, a first-in-class allosteric NEK7/NLRP3 inflammasome inhibitor given orally, in patients with lower-risk myelodysplastic syndromes (LR-MDS) (Press release, Halia Therapeutics, DEC 10, 2024, View Source [SID1234648981]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The initial cohort of 18 patients with LR-MDS demonstrated a hematological improvement-erythroid (HI-E) response to HT-6184 treatment following 16 weeks of monotherapy, exceeding the preset requirement of at least three responders. Having achieved this critical milestone, the trial now advances to its second stage enrolling an additional 8-10 patients to further validate HT-6184’s potential.

"The high frequency of erythroid response following treatment with HT-6184 validates the key importance of the NLRP3 inflammasome and myddosome pathways as pathogenetic drivers of ineffective hematopoiesis in MDS, offering the prospect of a safe and effective oral therapeutic for LR-MDS patients," said Alan List, MD Halia SAB Member.

"This trial represents a significant step forward in addressing the unmet needs of patients with LR-MDS," said Dr. David J. Bearss, Ph.D., President and CEO of Halia Therapeutics. "By targeting the underlying inflammatory signaling driving this condition, HT-6184 aims to transform treatment outcomes and improve quality of life for patients who currently face limited options."

The Phase 2 trial utilizes a Simon’s minimax two-stage design to evaluate the safety and efficacy of HT-6184 in up to 40 patients across multiple clinical sites in India. Primary endpoints include hematologic improvements such as transfusion dependency and changes in hemoglobin levels. Secondary endpoints assess HT-6184’s impact on biomarkers of inflammasome activation in MDS and the size of somatic gene mutation clones, offering a comprehensive view of its therapeutic potential.

The trial is expected to conclude by the end of Q2 2025. The results of this study are anticipated to provide pivotal data to support HT-6184’s continued clinical development and eventual regulatory submission.

About Myelodysplastic Syndromes (MDS): An Urgent Unmet Need

MDS is a group of hematologic cancers characterized by bone marrow dysfunction, leading to abnormal and underdeveloped blood cells. These conditions result in complications such as anemia, increased infection risk, and, in some cases, progression to acute myeloid leukemia. Current treatments are limited in efficacy and durability for patients with LR-MDS, underscoring the need for innovative therapeutic solutions. Novel oral agents are needed for the treatment of this disease to alleviate the need to go into the office for treatment either with an injection or needed infusion.

About HT-6184

HT-6184 is a groundbreaking drug candidate that targets the protein NEK7 through an allosteric mechanism. NEK7 plays a crucial role in the NLRP3 inflammasome, which is essential for its assembly and activity. In preclinical models, Halia demonstrated that inhibiting NEK7’s binding ability to NLRP3 disrupts inflammasome signaling and reduces the inflammatory response. HT-6184 prevents the formation of the NLRP3 inflammasome and promotes its disassembly once activated.

On December 10, 2024 Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer, reported results from an oral presentation at the 66 th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, reporting Phase 1 findings from the two-part IMproveMF study (Press release, Geron, DEC 10, 2024, View Source [SID1234648980]). The safety results from the dose escalation Part 1 suggest the tolerability of RYTELO (imetelstat), a first-in-class telomerase inhibitor, in combination with ruxolitinib as frontline therapy in patients with intermediate-1 (INT-1), intermediate-2 (INT-2) or high-risk (HR) myelofibrosis (MF). Based on the dose escalation findings in Part 1, imetelstat 9.4 mg/kg dosed every four weeks with ruxolitinib was the selected dose for the dose expansion Part 2 of the study, which is currently enrolling patients.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"As a telomerase inhibitor, the potential of imetelstat to affect the malignant clone differentiates it from any other drug currently approved or in development for myelofibrosis treatment. These early results also support the potential tolerability of imetelstat and ruxolitinib as a combination therapy and could have significant implications for future development efforts," said Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron. "Given these early findings from the IMproveMF study presented at ASH (Free ASH Whitepaper), we are now enrolling Part 2 of the study for dose confirmation and expansion at the highest dose level, imetelstat 9.4 mg/kg every 4 weeks, to further explore and confirm this dosing and schedule in combination with ruxolitinib as a potential frontline therapy in MF."

"Upon diagnosis, intermediate-1 and -2 and high-risk myelofibrosis patients typically receive ruxolitinib as the primary therapy, which reduces enlarged spleens and alleviates symptoms. These early results showing the tolerability of ruxolitinib combined with imetelstat in this patient population are highly encouraging, because as a non-JAK inhibitor treatment option with a potentially novel mechanism of action, imetelstat could provide an additive benefit, affecting the underlying malignant clones implicated in MF progression, when combined with ruxolitinib alone," said John Mascarenhas, M.D., Professor of Medicine at the Icahn School of Medicine at Mount Sinai and a principal investigator on the IMproveMF study, who delivered the oral presentation at ASH (Free ASH Whitepaper).

IMproveMF is an ongoing, multicenter Phase 1/1b trial that aims to evaluate the safety, pharmacokinetics (PK), and clinical activity of imetelstat in combination with ruxolitinib in patients with INT-1/INT-2/HR MF. As of the November 4, 2024 cutoff date, at least three patients had received each imetelstat dose level: Dose Level 1, imetelstat 4.7 mg/kg (n=3); Dose Level 2, imetelstat 6.0 mg/kg (n=3); Dose Level 3, imetelstat 7.5 mg/kg (n=4); and Dose Level 4, imetelstat 9.4 mg/kg (n=7). Ruxolitinib doses were individualized per patient. The PK profiles of imetelstat and ruxolitinib were consistent with previous monotherapy studies of imetelstat and ruxolitinib. At the time of this analysis, the median duration of imetelstat treatment for the seven patients in the imetelstat 9.4 mg/kg cohort was 12.1 weeks (range: 4.1-20.9 weeks).

The combination of imetelstat with ruxolitinib was well-tolerated, and no dose-limiting toxicities were reported at any imetelstat dose level within the first 28 days of Cycle 1. Grade 3 treatment-emergent adverse events (TEAEs) were reported in 47% (8/17) of patients, with anemia reported in 24% (4/17), neutropenia in 18% (3/17), leukopenia in 12% (2/17), and abdominal pain, fatigue, pneumonia and epistaxis each reported in 6% (1/17) of patients. No Grade 4 or 5 TEAESs were reported.

For patients in the 9.4 mg/kg imetelstat dose level selected for dose expansion in Part 2 of the study, hematology values, including hemoglobin, leukocytes, neutrophils and platelets, were stable over time. Across all four dose cohorts, average absolute change from baseline total symptom score (TSS) over week 12 was a median of –5 and maximum absolute reduction from baseline TSS up to Week 24 was a median of –5. A trend for dose-dependent spleen volume reduction (SVR) at Week 24 was observed in the first three doses. Further evidence is needed in the 9.4 mg/mg dose where Week 24 data were not available at the time of this analysis. Preliminary results showed variant allele frequency (VAF) reductions in JAK2, CALR, MPL and high molecular risk driver mutations across the four dose cohorts.

IMproveMF is actively enrolling patients for dose confirmation and expansion (NCT05371964). In parallel, the separate IMpactMF Phase 3 trial is ongoing in MF patients who are relapsed/refractory to JAK inhibitors (NCT04576156). This Phase 3 trial is designed to confirm the results from the IMbark Phase 2 study, where single-agent imetelstat treatment resulted in multiple clinically meaningful benefits, including symptom response and potential improvement in overall survival.

The ASH (Free ASH Whitepaper) presentation, titled "Trial Update from IMproveMF, an Ongoing, Open-Label, Dose-Escalation and -Expansion, Phase 1/1B Trial to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of the Novel Combination of Imetelstat with Ruxolitinib in Patients with Intermediate-1, Intermediate-2, or High-Risk Myelofibrosis (MF)," is available on Geron’s website in the investor section under publications.

About RYTELO (imetelstat)

RYTELO (imetelstat) is an FDA-approved oligonucleotide telomerase inhibitor for the treatment of adult patients with low-to-intermediate-1 risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia requiring four or more red blood cell units over eight weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs). It is indicated to be administered as an intravenous infusion over two hours every four weeks.

RYTELO is a first-in-class treatment that works by inhibiting telomerase enzymatic activity. Telomeres are protective caps at the end of chromosomes that naturally shorten each time a cell divides. In LR-MDS, abnormal bone marrow cells often express the enzyme telomerase, which rebuilds those telomeres, allowing for uncontrolled cell division. Developed and exclusively owned by Geron, RYTELO is the first and only telomerase inhibitor approved by the U.S. Food and Drug Administration.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Thrombocytopenia

RYTELO can cause thrombocytopenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased platelets occurred in 65% of patients with MDS treated with RYTELO.

Monitor patients with thrombocytopenia for bleeding. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer platelet transfusions as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended.

Neutropenia

RYTELO can cause neutropenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased neutrophils occurred in 72% of patients with MDS treated with RYTELO.

Monitor patients with Grade 3 or 4 neutropenia for infections, including sepsis. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended.

Infusion-Related Reactions

RYTELO can cause infusion-related reactions. In the clinical trial, infusion-related reactions occurred in 8% of patients with MDS treated with RYTELO; Grade 3 or 4 infusion-related reactions occurred in 1.7%, including hypertensive crisis (0.8%). The most common infusion-related reaction was headache (4.2%). Infusion-related reactions usually occur during or shortly after the end of the infusion.

Premedicate patients at least 30 minutes prior to infusion with diphenhydramine and hydrocortisone as recommended and monitor patients for one hour following the infusion as recommended. Manage symptoms of infusion-related reactions with supportive care and infusion interruptions, decrease infusion rate, or permanently discontinue as recommended.

Embryo-Fetal Toxicity

RYTELO can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RYTELO and for 1 week after the last dose.

ADVERSE REACTIONS

Serious adverse reactions occurred in 32% of patients who received RYTELO. Serious adverse reactions in >2% of patients included sepsis (4.2%) and fracture (3.4%), cardiac failure (2.5%), and hemorrhage (2.5%). Fatal adverse reactions occurred in 0.8% of patients who received RYTELO, including sepsis (0.8%).

Most common adverse reactions (≥10% with a difference between arms of >5% compared to placebo), including laboratory abnormalities, were decreased platelets, decreased white blood cells, decreased neutrophils, increased AST, increased alkaline phosphatase, increased ALT, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache.

Please see RYTELO (imetelstat) full Prescribing Information, including Medication Guide, available at View Source