On November 5, 2024 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported financial results for the quarter ended September 30, 2024, and highlighted select corporate milestones and progress on its key clinical development programs (Press release, Karyopharm, NOV 5, 2024, View Source [SID1234647730]).

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!

"This quarter, we delivered our third consecutive quarter of U.S. XPOVIO net product revenue growth in the highly competitive multiple myeloma marketplace. On our clinical pipeline, we are very excited with the change to our Phase 3 SENTRY myelofibrosis trial endpoints following engagement with the FDA, strengthening our confidence for a successful outcome for this trial. We continue to drive disciplined expense management and trial execution as we look forward to our next phase of growth with potential new indications in myelofibrosis and endometrial cancer," said Richard Paulson, President and Chief Executive Officer of Karyopharm.

"A significant unmet need in myelofibrosis remains, as less than half of patients achieve SVR35 with each of the approved JAKi inhibitors. I am encouraged by the Phase 1 trial which evaluated the combination of selinexor and ruxolitinib, as it shows an approximate doubling of SVR35 to 80% compared to historical JAKi monotherapy and a meaningful 18.5 point improvement in Abs-TSS at week 24 compared to baseline," said Dr. John Mascarenhas, Principal Investigator of the Phase 3 SENTRY trial, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders. "The change to Abs-TSS as a co-primary endpoint signifies a new era in the evaluation of combination therapy and reflects a growing willingness by the FDA to incorporate more sensitive methods of evaluating symptoms in trials with active comparators."

Third Quarter 2024 and Recent Highlights

XPOVIO Commercial Performance

Achieved U.S. net product revenue of $29.5 million for the third quarter of 2024, compared to $28.0 million for the second quarter of 2024 and $30.2 million for the third quarter of 2023.

XPOVIO net product revenue was supported by quarter-over-quarter double digit growth in demand, partially offset by higher gross-to-net quarter-over-quarter largely due to higher proportion of 340B book of business.

Continued quarter-over-quarter demand growth with strong demand growth in the community setting, which represents approximately 60% of overall net product revenues. In the academic setting, demand for XPOVIO grew quarter-over-quarter amidst ongoing competitive pressures with continued use of XPOVIO preceding and following T-cell therapies in later lines.

Expanded global patient access for selinexor in the third quarter of 2024 with favorable reimbursement decisions in France and Italy and additional regulatory approvals in Turkiye, South Korea, Thailand and Malaysia.
Research and Development (R&D) Highlights

Myelofibrosis

Following recent alignment with the FDA, absolute change in total symptom score (Abs-TSS) at Week 24 will replace total symptom improvement of ≥ 50% (TSS50) as a co-primary endpoint in the pivotal Phase 3 SENTRY trial of selinexor in combination with ruxolitinib in JAKi naive myelofibrosis. Abs-TSS measures the average improvement in patient symptom scores over 24 weeks relative to the patient’s baseline symptom score and is an accepted measure that has been used in other Phase 3 clinical trials in myelofibrosis to evaluate the benefit/risk of an add-on treatment, such as selinexor, to the current standard of care. Spleen volume reduction ≥35% (SVR35) at Week 24 will remain as a co-primary endpoint. These two co-primary endpoints will be tested sequentially starting with SVR35 followed by Abs-TSS.

Proactively increasing the total sample size of the SENTRY trial to approximately 350 patients to further increase the statistical powering. The trial continues to enroll patients with strong momentum with expected top-line data read-out remaining in the second half of 2025.

SENTRY-2 Phase 2 trial of selinexor monotherapy in JAKi naïve patients with moderate thrombocytopenia continues to enroll patients. The Company expects to present preliminary data from this trial in late 2024 or early 2025.
Endometrial Cancer

Long-term follow-up data from a pre-specified exploratory subgroup analysis of patients with advanced or recurrent TP53 wild-type endometrial cancer from the SIENDO study (NCT03555422) were presented with expanded exploratory quality-adjusted time without symptoms or toxicity analysis (Q-TWiST) for the proficient mismatched repair status (pMMR) TP53 wild-type subgroup at the International Gynecological Cancer Society (IGCS) conference in October 2024. These data showed the restricted mean Q-TWiST for selinexor to be 30 months compared to 17 months for placebo, resulting in a difference of 13 months.

Pivotal XPORT-EC-042 Phase 3 trial in TP53 wild-type endometrial cancer continues to enroll patients and is expected to read-out top-line data in early 2026.
Multiple Myeloma

Pivotal XPORT-MM-031 (EMN29) Phase 3 trial, in collaboration with the European Myeloma Network, evaluating an oral combination of selinexor 40 mg, pomalidomide and dexamethasone (SPd) in patients with previously treated multiple myeloma now has a targeted enrollment of approximately 120 patients which leverages the positively evolving data observed with SPd 40 mg. Pending regulatory agency feedback on the updated protocol, the Company will provide guidance on the top-line data readout timeline from this trial.
2024 Financial Outlook

Based on its current operating plans, Karyopharm has further narrowed its guidance for full year 2024 as follows:

Total revenue to be in the range of $145.0 million to $155.0 million as compared to the Company’s prior guidance of $145.0 million to $160.0 million. Total revenue consists of U.S. XPOVIO net product revenue and license, royalty and milestone revenue earned from partners.

U.S. XPOVIO net product revenue to be in the range of $110.0 million to $115.0 million as compared to the Company’s prior guidance of $105.0 million to $120.0 million.

R&D and selling, general and administrative (SG&A) expenses to be in the range of $255.0 million to $265.0 million, which includes approximately $20.0 million estimated non-cash stock-based compensation expense, as compared to the Company’s prior guidance of $250.0 million to $265.0 million.

The Company expects that its existing cash, cash equivalents and investments, the revenue it expects to generate from XPOVIO net product sales and its license agreements and ongoing disciplined expense management and cost saving measures, will be sufficient to fund its planned operations into the first quarter of 2026.1
1Excluding re-payment of $24.5 million aggregate principal amount of the Company’s remaining senior convertible notes due October 2025 (the 2025 Notes) and $25.0 million minimum liquidity covenant under the Company’s senior secured term loan due 2028. Taking into account the repayment of the 2025 Notes and the minimum liquidity covenant, Karyopharm expects its cash, cash equivalents and investments will be sufficient to fund its operations into the fourth quarter of 2025.

Third Quarter 2024 Financial Results

Total revenue: Total revenue for the third quarter of 2024 was $38.8 million, compared to $36.0 million for the third quarter of 2023.

Net product revenue: Net product revenue for the third quarter of 2024 was $29.5 million, compared to $30.2 million for the third quarter of 2023.

License and other revenue: License and other revenue for the third quarter of 2024 was $9.3 million, compared to $5.8 million for the third quarter of 2023. The increase was primarily due to $6.0 million of milestone-related revenue recognized from Menarini, which was related to reimbursement approvals for NEXPOVIO in the third quarter of 2024, partially offset by a $3.3 million decrease in revenue related to the reimbursement of development-related expenses from Menarini due to timing of reimbursement.

Cost of sales: Cost of sales for the third quarter of 2024 was $1.3 million, compared to $0.9 million for the third quarter of 2023. Cost of sales reflects the costs of XPOVIO units sold and the costs of products sold to our partners.

R&D expenses: R&D expenses for the third quarter of 2024 were $36.1 million, compared to $35.6 million for the third quarter of 2023. The increase was primarily due to an increase in clinical trial and related costs, mainly driven by increased activity in the ongoing Phase 3 SENTRY trial in myelofibrosis.

SG&A expenses: SG&A expenses for the third quarter of 2024 were $27.6 million, compared to $30.8 million for the third quarter of 2023. The decrease was primarily due to our ongoing cost reduction initiatives and lower headcount.

Interest income: Interest income for the third quarter of 2024 was $1.8 million, compared to $2.8 million for the third quarter of 2023 due to a lower cash and investments balance quarter-over-quarter.

Interest expense: Interest expense for the third quarter of 2024 was $11.4 million, compared to $6.1 million for the third quarter of 2023. The increase in interest expense was due to the Company’s new term loan and new secured convertible senior notes.

Other income: Other income for the third quarter of 2024 was $3.8 million due to a non-cash gain recognized in connection with the remeasurement of embedded derivatives and liability classified common stock warrants. The Company had immaterial other income in the third quarter of 2023.

Net loss: Karyopharm reported a net loss of $32.1 million, or $0.26 loss per basic and diluted share, for the third quarter of 2024, compared to a net loss of $34.5 million, or $0.30 loss per basic and diluted share, for the third quarter of 2023.

Cash position: Cash, cash equivalents, restricted cash and investments as of September 30, 2024 totaled $133.9 million, compared to $192.4 million as of December 31, 2023.

Conference Call Information

Karyopharm will host a conference call today, November 5, 2024, at 8:00 a.m. Eastern Time, to discuss the third quarter 2024 financial results and provide business highlights. To access the conference call, please dial (800) 836-8184 (local) or (646) 357-8785 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call, along with accompanying slides, will be available under "Events & Presentations" in the Investor section of the Company’s website. An archived webcast will be available on the Company’s website approximately two hours after the event.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with VELCADE (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) under accelerated approval in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in a growing number of ex-U.S. territories and countries, including Europe, the United Kingdom, China, South Korea and Israel, and is marketed in those areas by Karyopharm’s global partners. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326; Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).

In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody (Xd).

For the treatment of adult patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.

The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3‐4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations
Lactation: Advise not to breastfeed.

For additional product information, including full prescribing information, please visit www.XPOVIO.com.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch.

On November 5, 2024 Bristol Myers Squibb (NYSE: BMY) reported that the company will participate in two upcoming investor conferences in November 2024 (Press release, Bristol-Myers Squibb, NOV 5, 2024, View Source [SID1234647729]).

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!

Samit Hirawat, M.D., Executive Vice President, Chief Medical Officer and Head of Development, and Robert Plenge, M.D., Ph.D., Executive Vice President, Chief Research Officer, will take part in a fireside chat at Guggenheim’s Inaugural Healthcare Innovation Conference. They will answer questions about the company beginning at 10:00 a.m. ET on November 11, 2024.

David Elkins, Executive Vice President, Chief Financial Officer, will participate in a fireside chat at the 2024 Jefferies London Healthcare Conference on November 19, 2024. He will answer questions about the company beginning at 9:30 a.m. GMT (U.K.).

Investors and the general public are invited to listen to both sessions at their respective times by visiting View Source An archived edition of each session will be available following its conclusion.

On November 5, 2024 Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer, reported the publication of abstracts containing new data highlighting the potential of RYTELO (imetelstat), a first-in-class telomerase inhibitor, in myeloid hematologic malignancies. Six abstracts have been accepted for presentation at the 66 th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place from December 7-10, 2024, in San Diego, California and virtually (Press release, Geron, NOV 5, 2024, View Source [SID1234647726]).

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 look forward to collaborating with our trial investigators to present meaningful data updates across the imetelstat pipeline, which we believe continue to highlight telomerase inhibition as an important and powerful approach to treating myeloid hematologic malignancies," said Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron.

Lower-Risk Myelodysplastic Syndromes (LR-MDS)

Abstract #352: "Effect of Prior Treatments on the Clinical Activity of Imetelstat in Transfusion-Dependent Patients with Erythropoiesis-Stimulating Agent, Relapsed or Refractory/Ineligible Lower-Risk Myelodysplastic Syndromes"

Oral presentation on Saturday, December 7, 2024 at 4:45 p.m. PT by Uwe Platzbecker, M.D., Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, Leipzig University Hospital, Leipzig, Germany

This abstract evaluates the effect of prior treatments on the clinical activity of imetelstat in patients with red blood cell (RBC) transfusion-dependent (TD) LR-MDS in an analysis of imetelstat-treated patients pooled from the IMerge Phase 2, Phase 3 and QTc studies (N=226). The results suggest that imetelstat demonstrates RBC-transfusion-related clinical activity and increases in hemoglobin in these patients regardless of prior therapies, although there are limited data on outcomes in later lines of treatment.

"There are very few treatment options today for patients with lower-risk MDS who have symptomatic anemia and are transfusion dependent, which often results in patients having to cycle through available therapies. By pooling data across the IMerge clinical trial, we sought to understand the potential of treatment with imetelstat for these patients regardless of their prior treatment. Although we have small numbers in some cases, these data have important clinical implications, suggesting that these patients experienced a RBC-transfusion related clinical benefit and improvements in hemoglobin with imetelstat regardless of their prior treatment," said Dr. Platzbecker.

Therapy received prior to imetelstat treatment*

≥8-week RBC-TI

≥24-week RBC-TI

RBC Transfusion Reduction of ≥4 U/8 weeks

Hb Rise of ≥1.5 g/dL for ≥8 weeks

HI-E (IWG 2018)

ESA (n=204)

40%

28%

64%

33%

43%

Luspatercept (n=35)

29%

20%

69%

29%

26%

Lenalidomide (n=26)

23%

12%

54%

19%

31%

HMA (n=22)

14%

9%

50%

14%

18%

*Prior treatment was not mutually exclusive; patients may have received more than one prior therapy.

RBC-TI, red blood cell-transfusion independence; HI-E, hematologic improvement-erythroid; IWG, International Working Group; Hb, hemoglobin; ESA, erythropoiesis-stimulating agent; HMA, hypomethylating agent.

Additionally, in imetelstat-treated patients ineligible for ESA therapy (n=22) treated in the front-line, 36% and 14% achieved ≥8-week and ≥24-week RBC-TI, respectively, 41% met HI-E, 64% had a transfusion reduction of ≥4 U/8 weeks, and 2% had a Hb rise of ≥1.5 g/dL for ≥8 weeks.

Abstract #4590: "Initial Results from the QTc Substudy of the IMerge Phase 3 Trial Demonstrate Clinically Meaningful Efficacy, Manageable Safety, and Absence of Proarrhythmic Risk in Patients with Lower-Risk Myelodysplastic Syndromes Who Received Prior Therapies Beyond Erythropoiesis Stimulating Agents"

Poster presentation on Monday, December 9, 2024 from 6:00 p.m. – 8 p.m. PT by Rami S. Komrokji, M.D., Vice Chair, Malignant Hematology Department, Moffitt Cancer Center

This abstract reports the first efficacy and safety results from the ventricular repolarization IMerge QTc substudy conducted per FDA guidance. This substudy differed from the IMerge Phase 3 trial in its crossover design, by allowing prior lenalidomide and HMA therapy besides ESAs and by allowing lower-risk MDS patients with the del(5q) mutation. As of the data cutoff on May 10, 2024, no clinically meaningful effects of imetelstat on cardiac repolarization or other ECG parameters were observed. In the 51 total imetelstat-treated patients (35 randomized and 16 crossover), the median treatment duration was 29.3 weeks and the median (95% CI) duration of RBC-TI among ≥8-week RBC-TI responders was 52.6 weeks (40.9-non estimable). Subgroup analyses showed ≥8-week RBC-TI rates of 30% (7/23) and 50% (14/28) in patients with and without prior luspatercept, 38% (5/13) and 42% (16/38) in patients with and without prior lenalidomide, and 21% (3/14) and 49% (18/37) in patients with and without prior HMA use, respectively. No new safety signals emerged, and in the total imetelstat-treated population, Grade 3/4 neutropenia and thrombocytopenia by laboratory evaluation occurred in 65% (33/51) and 49% (25/51) of patients, respectively, of which most cases resolved to Grade ≤2 within four weeks; incidence was similar to the overall Phase 3 imetelstat-treated population. In this QTc substudy, efficacy and safety of imetelstat were comparable to that shown in the overall population of the IMerge Phase 3 trial, and notably, responses to imetelstat were seen in patients receiving prior treatments including luspatercept, lenalidomide, and HMAs.

Abstract #3210: "Correlation of Patient-Reported Outcomes with Red Blood Cell Transfusion Reduction and Rise in Hemoglobin in Patients with Lower-Risk Myelodysplastic Syndromes in the IMerge Trial"

Poster presentation on Sunday, December 8, 2024 from 6:00 p.m. – 8 p.m. PT by Mikkael Sekeres, MD, University of Miami Health System and Sylvester Comprehensive Cancer Center

This abstract reports on post-hoc analyses of the patient-reported outcome (PRO) population from the IMerge Phase 3 clinical trial (N=175; 118 treated with imetelstat and 57 treated with placebo). PROs were assessed with validated Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, Functional Assessment of Cancer Therapy-Anemia (FACT-An), and the Quality of Life in Myelodysplasia Scale (QUALMS) questionnaires. In the ring sideroblast positive (RS+) and RS negative (RS-) groups, respectively, sustained, meaningful improvement in fatigue was achieved by 55% and 43% of imetelstat-treated patients; differences (95% CI) versus placebo appeared to favor imetelstat (9% [−12, 29] for RS+ and 13% [−15, 36] for RS−). Similarly, in patients with prior transfusion burdens of 4-6 U/8 weeks or >6 U/8 weeks, respectively, sustained improvement in fatigue was achieved by 44% and 57% of imetelstat-treated patients; differences (95% CI) versus placebo appeared to favor imetelstat (8% [−15, 29] for 4-6 U/8 weeks and 11% [−13, 34] for >6 U/8 weeks). Similar to the RBC-TI response and improvement in fatigue association, for imetelstat-treated patients with versus in those without a ≥1.5-g/dL increase in hemoglobin lasting ≥8 weeks, improvements in fatigue were seen in 70% (28/40) versus 40% of patients, respectively (31/78; nominal P-value=.003); in those with versus in those without transfusion reduction of ≥4 U/8 weeks, improvements were seen in 69% (49/71) versus 21% of patients (10/47; nominal P-value <.001). The QUALMS and FACT-An analyses suggested that imetelstat maintained QOL and anemia symptoms, while placebo recipients experienced worsening QOL and anemia symptoms.

"Low quality of life can be one of the most devastating and burdensome impacts of living with lower-risk MDS, particularly when patients are anemic and transfusion-dependent. The sustained improvement in fatigue and maintenance of quality of life and anemia symptoms with imetelstat shown in these post-hoc analyses are meaningful and very encouraging as we aim to improve outcomes for these patients," Dr. Platzbecker continued.

Myelofibrosis (MF)

Abstract #998: "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)"

Oral presentation on Monday, December 9, 2024 at 4:45 p.m. PT by John Mascarenhas, M.D., Professor of Medicine at the Icahn School of Medicine at Mount Sinai

This abstract reports the first safety results from the dose escalation Part 1 of the Phase 1/1B IMproveMF clinical trial, in which 13 patients were enrolled as of July 10, 2024. At least three patients received each dose level of imetelstat and doses of ruxolitinib were individualized per patient. No dose limiting toxicities (DLTs) were observed, and adverse events were consistent with those observed in other clinical trials of imetelstat. Imetelstat and ruxolitinib pharmacokinetic profiles in the combination study were similar to previous monotherapy studies. These early results show potential for the tolerability of the combination of imetelstat and ruxolitinib in this frontline MF patient population.

"These early results support the potential tolerability of imetelstat as a combination therapy and could have significant implications for future development efforts," continued Dr. Feller.

Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes (HR-MDS)

Abstract #3222: "A Phase II Study Evaluating the Efficacy and Safety of Imetelstat in Patients with Advanced Myelodysplastic Neoplasms or AML Failing HMA-Based Therapy – Interim Analysis Results of the IMpress Study"

Poster presentation on Sunday, December 8, 2024 from 6:00 p.m. – 8 p.m. PT by Uwe Platzbecker, M.D.

This abstract, submitted by Geron collaborators, provides an interim analysis from the Phase 2 IMpress trial, led by the European Myelodysplastic Neoplasms Cooperative Group (EMSCO), which is evaluating imetelstat in patients with HR-MDS or AML, refractory, relapsing or intolerant to either azacitidine or decitabine, or venetoclax plus azacitidine. Between June and October 2023, 23 patients (6 HR-MDS, 17 AML) received at least one dose of imetelstat with an average of 2.8 doses administered per patient. In this first part of the trial, none of the 23 treated patients reached the primary endpoint visit, which was scheduled after 4 cycles of treatment. Sixteen of these 23 patients reached the preliminary disease assessment visit after two cycles of imetelstat; one patient showed a response in hematologic improvements in the erythroid and platelet lineages (HI-E and HI-P), 7 patients had stable disease and 8 patients had progressive disease. Short-term transient improvement in hematological values was observed in individual cases. In patients on the LR-MDS dosing schedule of every four weeks, imetelstat showed some antiproliferative effects, including a decline in blasts and leukocytes. Overall, no new safety signals occurred beyond those already known for imetelstat. A total of 30 serious adverse events (SAEs) occurred in 18 patients of which 21 SAEs required hospitalizations. Based on the observations in this first cohort, the protocol was amended to a more frequent dosing schedule for a second cohort of patients being enrolled and treated with this modified schedule starting in August 2024.

Abstract #52: "Overcoming Ven/Aza Resistance Through Imetelstat-Mediated Lipophagy in Acute Myeloid Leukemia"

Oral presentation on Saturday, December 7, 2024 at 10:15 a.m. PT by Claudia Bruedigam, Team Head, Leukaemia Metabolism Laboratory, QIMR Berghofer Medical Research Institute, Queensland, Australia

This abstract, submitted by Geron collaborators, shares pre-clinical data identifying imetelstat-mediated, ferroptosis-associated lipidomic alterations in AML cells that correlate with imetelstat treatment responses in vivo. These mechanistic insights may be leveraged to develop an optimized therapeutic strategy using imetelstat to target venetoclax/azacitidine resistant AML subclones.

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

On November 5, 2024 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that its research collaborators at Meharry Medical College will present a poster detailing positive preclinical data from a study of the Company’s lead drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid)evaluating TUSC2’s role in modulating immune responses in cancer (Press release, Genprex, NOV 5, 2024, View Source [SID1234647725]). The poster will be presented at the 39th Annual Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Meeting being held November 6-10, 2024 in Houston, Texas.

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 pleased to have our academic partner present their findings on REQORSA at this prestigious cancer meeting, expanding on REQORSA’s ability to modulate immune responses in cancer," said Ryan Confer, President and Chief Executive Officer at Genprex. "We continue to bolster the growing body of evidence supporting REQORSA’s anti-tumor mechanisms, highlighting its therapeutic potential to treat a variety of cancers."

The Genprex-supported poster to be presented at the 2024 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting:

Title: "TUSC2 Modulates Cancer Immune Responses"

Collaborator: Meharry Medical College

In this study, researchers used comparative flow cytometry analysis of splenocytes, lymph nodes cells, and tumor infiltrating leucocytes (TILs) from TUSC2 Knock Out (KO) and TUSC2 Wild Type (WT) mice. FACS analysis was focused on the differences in T reg, Cytotoxic T cells and NK cells between the two mice groups. For analysis of immune responses to tumors, researchers challenged two groups of TUSC2 KO mice with syngeneic 129 Sv background metastatic lung cancer 344SQ cells and injected one group with TUSC2-expressing lipoparticles (REQORSA).

In the REQORSA supplemented group, the tumor growth was diminished. A significant reduction in T reg and significant increase in Cytotoxic T cells and NK cells were observed within TILs. A significant increase in Granzyme B expression within Cytotoxic T cells and NK cells was shown in REQORSA supplemented mice compared to the control group.

This research expanded on previous studies showing that REQORSA modulates immune cells within the Tumor Micro Environment. REQORSA-dependent changes in immune cells correlated with the reduction in tumor size in the experimental group, indicating that REQORSA may carry anti-tumor potential even for individuals with low overall TUSC levels in various tissues due to aging, chronic inflammation, metabolic diseases, etc. This research documents that REQORSA treatment has been shown to lead to increased immune response against tumors in TUSC2 KO mice.

TUSC2 is the tumor suppressor gene used in REQORSA. REQORSA consists of a TUSC2 gene expressing plasmid encapsulated in non-viral lipid-based nanoparticles in a lipoplex form (the Company’s Oncoprex Delivery System), which has a positive charge. REQORSA is injected intravenously and specifically targets cancer cells. REQORSA is designed to deliver the functioning TUSC2 gene to negatively charged cancer cells while minimizing uptake by normal tissue. Laboratory studies conducted at MD Anderson show that the uptake of TUSC2 in tumor cells in vitro after REQORSA treatment was 10 to 33 times the uptake in normal cells.

Following the conference, the poster will be made available to download on Genprex’s website, where it can be reviewed in greater detail.

On November 5, 2024 Exact Sciences Corp. (Nasdaq: EXAS), a leading provider of cancer screening and diagnostic tests, reported that the Company generated revenue of $709 million for the third quarter ended September 30, 2024, compared to $628 million for the same period of 2023 (Press release, Exact Sciences, NOV 5, 2024, View Source [SID1234647724]).

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 Exact Sciences’ team is helping eradicate cancer while strengthening our platform and growing our business efficiently," said Kevin Conroy, chairman and CEO. "During the third quarter, we delivered test results to more patients than ever before, improved profitability, and achieved key milestones in our pipeline of innovative cancer diagnostics. While we have made progress, our execution during the third quarter and updated outlook for the full year don’t reflect our full potential. We plan to accelerate growth in 2025, and our long-term outlook remains strong."

Third-quarter 2024 financial results

For the three-month period ended September 30, 2024, as compared to the same period of 2023 (where applicable):

Total revenue was $709 million, an increase of 13 percent on a reported and core revenue basis
Screening revenue was $545 million, an increase of 15 percent
Precision Oncology revenue was $164 million, an increase of 5 percent on a reported and core revenue basis
Gross margin including amortization of acquired intangible assets was 69 percent, and non-GAAP gross margin excluding amortization of acquired intangible assets was 72 percent
Other operating income was $3 million compared to $72 million, which included a gain related to the sale of the Oncotype DX Genomic Prostate Score Test in third-quarter 2023
Net loss was $38 million, or $0.21 per basic and diluted share, a reduction of $39 million, or $0.21 per basic and diluted share
Adjusted EBITDA was $99 million an increase of $42 million, and adjusted EBITDA margin was 14 percent, an increase of 500 basis points
Operating cash flow was $139 million and free cash flow was $113 million, increases of $114 million and $113 million, respectively
Cash, cash equivalents, and marketable securities were $1.02 billion at the end of the quarter
Screening primarily includes laboratory service revenue from Cologuard tests and PreventionGenetics. Precision Oncology includes laboratory service revenue from global Oncotype DX and therapy selection tests.

Platform and pipeline advancements

The Company’s ExactNexus technology platform allows Exact Sciences to connect electronically with patients, health systems, healthcare professionals, and payers. The digital tools and data embedded within the ExactNexus platform enable personalized customer experiences, creating a streamlined process for accessing information, enhancing patient engagement, and improving health outcomes. This approach contributed to strong growth in Cologuard test utilization among rescreen patients and within care gap programs during the third quarter.

Exact Sciences received FDA approval for the Cologuard Plus test, its next-generation Cologuard test. The Cologuard Plus test detects cancers and precancerous polyps with even greater sensitivity than the Cologuard test while reducing false positives by more than 30 percent. This advancement enhances the Company’s screening capabilities and reinforces its commitment to delivering high-quality, non-invasive options for patients. With the Cologuard Plus test, the Company expects to secure a higher price through an established Medicare pathway.

In the third quarter, the Company also presented data for its blood-based colorectal cancer screening test, showcasing a sensitivity of 88% for colorectal cancer and 31% for advanced precancerous lesions at 90% specificity. These results show the potential of the Company’s novel marker panel to detect advanced precancerous lesions and cancers at an attractive cost profile. This innovation is expected to provide average-risk patients with another screening option, reinforcing the power of the Company’s unique scientific approach.

Exact Sciences secured acceptance from a peer-reviewed journal for its first publication on the Oncodetect test, its molecular residual disease and recurrence monitoring test. These data are currently under embargo and are expected to be shared in January 2025. With nearly 6 million cancer survivors in the U.S. who could benefit from residual and recurrent disease testing, the need is urgent – yet less than 5% are currently receiving the vital testing today. This recognition highlights the scientific rigor behind the product and positions the Oncodetect test as a leading solution for monitoring residual disease and cancer recurrence.

The Company also shared evidence supporting its blood-based multi-cancer screening test, assessing organ-specific performance of methylation and protein biomarkers in a prospectively collected cohort of samples from its ASCEND 2 study. The analysis indicated an overall sensitivity of 55% in cancers without standard-of-care screening options (excluding lung), and 64% in the six most aggressive cancers with the shortest survival rates, with a specificity of 98.5%. These findings highlight the potential clinical value of using multiple biomarkers to detect various cancer types, including the most aggressive and those without recommended screening options.

2024 outlook

The Company has updated its full-year 2024 revenue and adjusted EBITDA guidance:

Prior guidance

November 5 update

Total revenue

$2.810 – $2.850 billion

$2.730 – $2.750 billion

Screening

$2.155 – $2.175 billion

$2.080 – $2.095 billion

Precision Oncology

$655 – $675 million

$650 – $655 million

Adjusted EBITDA

$335 – $355 million

$310 – $320 million

Third-quarter 2024 conference call & webcast

Company management will host a conference call and webcast on Tuesday, November 5, 2024, at 5 p.m. ET to discuss third-quarter 2024 results. The webcast will be available at exactsciences.com. Domestic callers should dial 888-330-2384 and international callers should dial +1-240-789-2701. The access code for both domestic and international callers is 4437608. A replay of the webcast will be available at exactsciences.com. The webcast, conference call, and replay are open to all interested parties.