On February 22, 2024 Asieris Pharmaceuticals (Stock Code: 688176.SH), a global biopharmaceutical leader in the discovery, development, and commercialization of innovative drugs for genitourinary tumors and related diseases reported that the international multicenter Phase III clinical study of its non-surgical treatment for cervical HSIL product APL-1702, will be presented for the first time in the form of an oral presentation at the 2024 European Research Organization on Genital Infection and Neoplasia (EUROGIN), to be held on March 13-16 (Press release, Asieris Pharmaceuticals, FEB 22, 2024, View Source [SID1234640398]).

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Oral presentation (Abstract No.6802) Photodynamic therapy with APL-1702 for high-grade squamous intraepithelial lesions (HSIL): results from a randomized phase Ⅲ global study (YHGT-CEV-1/APRICITY)

This study is a prospective, randomized, double-blind, placebo-controlled international multicenter Phase III clinical trial designed to evaluate the efficacy and safety of APL-1702 for the treatment of cervical HSIL. It is led by Academy Member Dr. Jinghe Lang from Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, and has enrolled 402 participants. The trial met its primary endpoint, together with a robust safety profile. APL-1702 holds the potential to become the world’s first non-surgical product with proven clinical efficacy against cervical HSIL.

EUROGIN is the leading international multidisciplinary Congress on Human Papillomavirus (HPV), aims to translate scientific and evidence-based research into clinical practice, accelerating the reduction of the burden of HPV-related cancers and their mortality.

On February 22, 2024 Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on its Phase III clinical trial, Flamingo-01, which is evaluating GLSI-100, an immunotherapy to prevent breast cancer recurrences in patients who have previously undergone surgery, reported the following update on the expansion of the clinical trial into Europe (Press release, Greenwich LifeSciences, FEB 22, 2024, https://investor.greenwichlifesciences.com/news-events/press-releases/detail/78/protocol-accepted-by-european-regulators [SID1234640397]).

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The Company’s application to expand Flamingo-01 into Europe has been reviewed by European Medicines Agency (EMA) through EMA’s Clinical Trials Information System (CTIS). The Company was informed that the manufacturing, non-clinical, clinical, statistical, and regulatory sections of its application are acceptable and the regulators’ requests for information have been addressed. The regulators have thus approved the clinical trial, marking a major milestone for the Company.

The 5 individual countries in Europe will now make a final determination, and if acceptable, they will allow the first group of approximately 105 sites in Europe to begin initiation and activation. Once an individual site has been activated patients can be screened and enrolled.

CEO Snehal Patel commented, "Our interactions with EMA and the 5 participating countries through the CTIS process provided great insight into EMA’s expectations for a marketing license application in Europe for GLSI-100. We will continue the dialogue with EMA regulators as we operate Flamingo-01 in Europe, which will help us prepare for an EU licensing application in the future in parallel to filing a BLA in the US."

About Flamingo-01 and GLSI-100

Flamingo-01 (NCT05232916) is a Phase III clinical trial designed to evaluate the safety and efficacy of GLSI-100 (GP2 + GM-CSF) in HER2/neu positive breast cancer patients who had residual disease or high-risk pathologic complete response at surgery and who have completed both neoadjuvant and postoperative adjuvant trastuzumab based treatment. The trial is led by Baylor College of Medicine and currently includes US clinical sites from university-based hospitals and cooperative networks with plans to expand into Europe and to open up to 150 sites globally. In the double-blinded arms of the Phase III trial, approximately 500 HLA-A*02 patients will be randomized to GLSI-100 or placebo, and up to 250 patients of other HLA types will be treated with GLSI-100 in a third arm. The trial has been designed to detect a hazard ratio of 0.3 in invasive breast cancer-free survival, where 28 events will be required. An interim analysis for superiority and futility will be conducted when at least half of those events, 14, have occurred. This sample size provides 80% power if the annual rate of events in placebo-treated subjects is 2.4% or greater.

For more information on Flamingo-01, please visit the Company’s website here and clinicaltrials.gov here. Contact information and an interactive map of the majority of participating clinical sites can be viewed under the "Contacts and Locations" section. Please note that the interactive map is not viewable on mobile screens. Related questions and participation interest can be emailed to: [email protected]

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 282,000 new breast cancer patients and 3.8 million breast cancer survivors in 2021. HER2/neu (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels.

On February 22, 2024 Moderna, Inc. (NASDAQ:MRNA) reported financial results and provided business updates for the fourth quarter and fiscal year 2023 (Press release, Moderna Therapeutics, FEB 22, 2024, View Source/news/news-details/2024/Moderna-Reports-Fourth-Quarter-and-Fiscal-Year-2023-Financial-Results-and-Provides-Business-Updates/default.aspx" target="_blank" title="View Source/news/news-details/2024/Moderna-Reports-Fourth-Quarter-and-Fiscal-Year-2023-Financial-Results-and-Provides-Business-Updates/default.aspx" rel="nofollow">View Source [SID1234640396]).

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"2023 was a year of transition for Moderna as we adapted to the endemic market. At the same time, our development team made significant pipeline advancements across infectious diseases, oncology and rare diseases, while our commercial team increased our COVID-19 market share in the U.S.," said Stéphane Bancel, Chief Executive Officer of Moderna. "We look forward to the anticipated approvals of our RSV vaccine beginning in the first half of the year. With multiple upcoming Phase 3 data readouts in 2024, we remain focused on commercial execution and continued investment in our pipeline with financial discipline."

Recent progress includes:

Commercial Updates

COVID-19: The Company reported $2.8 billion in Spikevax (COVID-19 vaccine) sales in the fourth quarter of 2023, which includes $0.8 billion of U.S. sales and $2 billion of international sales. This led to $6.7 billion in vaccine sales for fiscal 2023, consistent with the previously communicated financial framework of at least $6 billion.

Moderna achieved 48% cumulative market share1 in the U.S. retail segment during the fall 2023 COVID season, up from 37% in 2022. Moderna took specific actions in 2023 to transition to a seasonal endemic market including the resizing of its manufacturing footprint to improve cash flow, the flattening of its commercial structure to drive sales execution, and the focusing of its investments toward near-term growth drivers.

The Company is reaffirming its 2024 product sales outlook as it enters the second year of the U.S. commercial endemic COVID market with increased clarity of market size and dynamics. Moderna continues to focus on public health efforts to increase vaccination coverage rates globally for the 2024/2025 season to reduce the substantial burden of COVID-19. The Company is also prioritizing key international markets for greater commercial focus and is participating in the EU Health Emergency and Response Authority’s tendering procedure for up to 36 million doses of mRNA COVID-19 vaccines per year for up to four years.

RSV: The Company continues to expect initial regulatory approvals of its RSV vaccine (mRNA-1345) starting in the first half of 2024.

Moderna is well-prepared for the launch of its second respiratory vaccine, which will build upon the success of its commercial efforts in the fall COVID-19 market. The Company is encouraged by early indications of widespread consumer awareness and established demand in the RSV market, which Moderna will enter with a strong competitive profile with robust efficacy data, a well-established safety and tolerability profile, and as the only pre-filled syringe (PFS) product available at the time of launch. The PFS ready-to-use formulation will save pharmacists and clinicians time as well as potentially help reduce administration errors.

The PDUFA (Prescription Drug User Fee Act) action date for mRNA-1345 is May 12, 2024, by which time the Company expects the U.S. FDA’s response to its Biologics License Application (BLA). If the outcome is positive, the Company anticipates that the U.S. CDC Advisory Committee on Immunization Practices (ACIP) will include mRNA-1345 on the agenda of its June 26-28 meeting. Assuming that corresponding marketing authorizations would be granted as expected, the Company also plans to launch its RSV vaccine in Australia and Germany in 2024 and other markets in 2025 due to regulatory and tender timing.

Fourth Quarter 2023 Financial Results

Revenue: Total revenue for the fourth quarter of 2023 was $2.8 billion, a decrease from $5.1 billion in the same period in 2022, primarily due to a reduction in sales of the Company’s COVID-19 vaccine. Net product sales for the fourth quarter of 2023 were $2.8 billion, representing a 43% decline compared to the same period in 2022, primarily driven by lower sales volume, partially offset by a higher average selling price. Net product sales in the fourth quarter of 2023 include the recognition of $0.6 billion from deferred revenue, related to Gavi, the Vaccine Alliance.

Cost of Sales: Cost of sales for the fourth quarter of 2023 totaled $929 million, which included third-party royalties of $125 million, or 33% of net product sales, compared to 39% of net product sales for the fourth quarter of 2022. In the third quarter of 2023, the Company embarked on a strategic initiative aimed at optimizing the cost structure of its COVID-19 business, with an emphasis on resizing its manufacturing cost structure. The initiative involved scaling down the Company’s capacity and commitments with its third-party contract manufacturing organizations (CMOs), reevaluating its raw material inventory levels, and reducing its purchase commitments related to raw materials that were not expected to be consumed before expiration. As a part of this strategic effort during the fourth quarter of 2023, the Company incurred, as expected, additional charges of $169 million, primarily related to the wind-down of certain contract manufacturing operations. Additionally, cost of sales also includes an inventory write-down of $322 million, reflecting revised demand forecasts as the Company adapts to the end-of-season trends.

Research and Development Expenses: Research and development expenses for the fourth quarter of 2023 increased by 16% to $1.4 billion, compared to the same quarter of 2022. The growth in spending was largely driven by increased clinical manufacturing activities, notably with respect to the Company’s RSV vaccine, cytomegalovirus (CMV) vaccine, combination vaccine against flu and COVID-19, as well as its individualized neoantigen therapy. The increase also included an upfront payment of $120 million associated with the strategic research and development collaboration with Immatics.

Selling, General and Administrative Expenses: Selling, general and administrative expenses for the fourth quarter of 2023 increased by 25% to $470 million, in comparison to the fourth quarter of 2022. The growth in spending was primarily due to increased personnel-related costs and commercial and marketing expenses, driven by the expansion of commercial operations, particularly in the U.S. market.

Income Taxes: Income tax benefit for the fourth quarter of 2023 was $147 million, largely attributable to the tax benefits as part of finalizing our 2022 U.S. tax return.

Net Income: Net income was $217 million for the fourth quarter of 2023, compared to $1.5 billion for the fourth quarter of 2022, primarily driven by lower COVID-19 product sales.

Earnings Per Share: Diluted earnings per share was $0.55 for the fourth quarter of 2023, compared to $3.61 for the fourth quarter of 2022.

Full Year 2023 Financial Results

Revenue: Total revenue was $6.8 billion for the full year 2023, compared to $19.3 billion in 2022. The decrease in total revenue for 2023 was mainly due to a decline in sales of the Company’s COVID-19 vaccine. Net product sales for 2023 were $6.7 billion, a decrease of 64% from 2022, driven by lower vaccination rates. Net product sales include the recognition of $0.6 billion from deferred revenue, related to Gavi, the Vaccine Alliance.

Cost of Sales: Cost of sales for the full year 2023 was $4.7 billion, or 70% of net product sales, inclusive of third-party royalties of $301 million, inventory write-downs of $2.2 billion, unutilized manufacturing capacity and wind-down costs of $981 million, and losses on firm purchase commitments and cancellation fees of $205 million. Cost of sales includes a total of $1.6 billion, resulting from the Company’s strategic initiative to resize its manufacturing cost structure that was launched in the third quarter of 2023. Cost of sales, as a percentage of net product sales, increased by 41 percentage points to 70%, from 29% in 2022. The increase in cost of sales as a percentage of net product sales was primarily due to the strategic initiative and other aforementioned charges (excluding royalties) over lower net product sales, driven by a decline in product demand and increased product seasonality.

Research and Development Expenses: Research and development expenses increased by 47% to $4.8 billion for 2023, compared to 2022. The increase in spending in 2023 was mainly attributable to increases in clinical trial and clinical manufacturing expenses, personnel-related costs, and consulting and outside services, largely driven by the Company’s late-stage clinical studies for the RSV vaccine, CMV vaccine, combination vaccine against seasonal influenza and COVID-19, and the individualized neoantigen therapy program, as well as continued development of the Company’s pipeline.

Selling, General and Administrative Expenses: Selling, general and administrative expenses increased by 37% to $1.5 billion for 2023, compared to 2022. The increase in spending in 2023 was primarily attributable to the Company’s continued corporate expansion, particularly in the commercial area.

Income Taxes: Income tax provision for the full year 2023 was $772 million, which was primarily driven by a non-cash charge related to a valuation allowance on deferred tax assets.

Net Income (Loss): Net loss for the full year 2023 was $(4.7) billion, compared to a net income of $8.4 billion in 2022.

Earnings (Loss) Per Share: Diluted loss per share for the full year 2023 was $(12.33), compared to a diluted earnings per share of $20.12 in 2022.

Cash Position: Cash, cash equivalents and investments as of December 31, 2023, and December 31, 2022, were $13.3 billion and $18.2 billion, respectively. The decrease in cash position in 2023 was largely attributable to the full year’s operating loss and the repurchases of the Company’s common stock during the first half of the year.

2024 Financial Framework

Revenue: The Company expects revenue of approximately $4 billion for 2024 from its respiratory franchise.

Cost of Sales: The Company expects cost of sales for 2024 to be approximately 35% of product sales for the year.

Research and Development Expenses: The Company expects full-year 2024 research and development expenses of approximately $4.5 billion, compared to $4.8 billion in 2023.

Selling, General and Administrative Expenses: The Company expects full-year 2024 selling, general and administrative expenses of approximately $1.3 billion, compared to $1.5 billion in 2023.

Income Taxes: The Company anticipates its full-year tax expense to be negligible.

Capital Expenditures: The Company expects capital expenditures for 2024 of approximately $0.9 billion.

Cash and Investments: The Company expects 2024 year-end cash and investments of approximately $9 billion.

Recent Progress and Upcoming Late-Stage Pipeline Milestones

With nine late-stage programs, Moderna continues to advance its pipeline and expects numerous product milestones in 2024 across its vaccines and therapeutics portfolio.

Respiratory vaccines:

RRespiratory syncytial virus (RSV) vaccine: Moderna has filed for regulatory approvals for its vaccine for the prevention of RSV-associated lower respiratory tract disease (RSV-LRTD) and acute respiratory disease (ARD) in adults ages 60 years or older (mRNA-1345). The regulatory applications are based on positive data from the pivotal ConquerRSV study, a randomized, double-blind, placebo-controlled study of approximately 37,000 adults, 60 years or older. The trial met both its primary efficacy endpoints, with a vaccine efficacy (VE) of 83.7% (95.88% CI: 66.1%, 92.2%; p<0.0001) against RSV-LRTD as defined by two or more symptoms, and a VE of 82.4% (96.36% CI: 34.8%, 95.3%; p=0.0078) against RSV-LRTD defined by three or more symptoms. Most solicited adverse reactions were mild to moderate, and no cases of Guillain-Barre Syndrome (GBS) have been reported with mRNA-1345 in the Phase 3 RSV trial. These data were published in the New England Journal of Medicine in December 2023. Follow-up data from a Phase 3 RSV study with a median follow-up duration of 8.6 months, with a range of 15 days to 530 days, and including subjects from the Northern and Southern Hemispheres was recently presented at the RSVVW’24 conference. In this supplemental analysis, mRNA-1345 maintained durable efficacy, with sustained VE of 63.3% (95.88% CI: 48.7%, 73.7%) against RSV-LRTD including two or more symptoms. VE was 74.6% (95% CI, 50.7-86.9) against RSV-LRTD with ≥2 symptoms, including shortness of breath and 63.0% (95% CI, 37.3-78.2) against RSV-LRTD including three of more symptoms. The stringent statistical criterion of the study, a lower bound on the 95% CI of >20%, continued to be met for both endpoints. As mentioned above, the Company expects regulatory approvals beginning in the first half of 2024.
Seasonal flu vaccine: Moderna’s seasonal flu vaccine (mRNA-1010) demonstrated consistently acceptable safety and tolerability across three Phase 3 trials. In the most recent Phase 3 trial (P303), mRNA-1010 met all immunogenicity endpoints, demonstrating higher titers compared to a currently licensed standard-dose flu vaccine. mRNA-1010 has also shown higher or comparable titers compared to a currently licensed enhanced flu vaccine (Fluzone HD) in a separate Phase 1/2 study. The Company is in ongoing discussions with regulators and intends to file in 2024.

Next-generation COVID-19 vaccine: Moderna’s Phase 3 study of its next-generation COVID-19 vaccine (mRNA-1283), which is designed to be refrigerator-stable, is fully enrolled. The Company anticipates data from the study in the first half of 2024.

Seasonal flu + COVID vaccine: Moderna’s Phase 3 trial of its combination vaccine against seasonal flu and COVID-19 (mRNA-1083) is fully enrolled. The Company anticipates data from the study in 2024.
Latent and other vaccines:

CMV vaccine: The pivotal Phase 3 study of Moderna’s CMV vaccine candidate (mRNA-1647) is fully enrolled and accruing cases, evaluating its efficacy, safety and immunogenicity in the prevention of primary infection in women of childbearing age. The Company anticipates potential efficacy data from the study in 2024.
Oncology therapeutics:

Individualized Neoantigen Therapy (INT): Moderna continues to demonstrate the potential clinical benefit of its INT program (mRNA-4157). In partnership with Merck, Phase 3 trials continue to enroll in resected high-risk (stage III/IV) melanoma and completely resected stage II, IIIA or IIIB non-small cell lung cancer. Moderna and Merck plan to initiate clinical studies in additional tumor types in 2024. In December 2023, the Company announced results of a three-year analysis of its Phase 2b study evaluating INT in combination with KEYTRUDA, Merck’s anti-PD-1 therapy, in patients with resected high-risk melanoma. Compared to KEYTRUDA alone, this combination continued to show an improvement in recurrence-free survival, reducing the risk of recurrence or death by 49%, as well as in distant metastasis-free survival, reducing the risk of developing distant metastasis or death by 62%. Additionally, the results of the primary analysis at two-year follow-up of its Phase 2 study were published in The Lancet. The Company has purchased and started build-out of a manufacturing site in Marlborough, MA, to enable commercial scale of its INT program.
Rare disease therapeutics:

Propionic acidemia (PA) & methylmalonic acidemia (MMA): The Company expects to advance its PA (mRNA-3927) and MMA (mRNA-3705) programs into registrational studies in 2024.
Moderna Corporate Updates

Highlighted the Company’s digital and AI strategy and progress at its second Digital Investor Event on November 8, 2023.
Reviewed the Company’s progress and ambitions during its second Environmental, Social and Governance (ESG) Investor Event on December 7, 2023.
Published Moderna CEO Stéphane Bancel’s annual letter to shareholders on January 2, 2024.
Provided business and pipeline updates at the 42nd Annual J.P. Morgan Healthcare Conference on January 8, 2024.
Scheduled the Moderna Annual Meeting of Shareholders to be held on Monday, May 6, 2024, at 8:00 a.m. ET.
Company accolades:

Moderna topped BioSpace’s Best Places to Work in Biopharma ranking for the third consecutive year.
Moderna was named to Fortune’s list of World’s Most Admired Companies for the first time.
Stéphane Bancel, Chief Executive Officer of Moderna, was elected to the National Academy of Engineering.
Key 2024 Investor and Analyst Event Dates

Vaccines Day: March 27 at 9 a.m. ET
R&D Day: September 12
Investor Call and Webcast Information

Moderna will host a live conference call and webcast at 8:00 a.m. ET on February 22, 2024. To access the live conference call via telephone, please register at the link below. Once registered, dial-in numbers and a unique pin number will be provided. A live webcast of the call will also be available under "Events and Presentations" in the Investors section of the Moderna website.

Telephone: https://register.vevent.com/register/BI0c7f1372a78b427d9f354a2630418034
Webcast: View Source
The archived webcast will be available on Moderna’s website approximately two hours after the conference call and will be available for one year following the call.

On February 22, 2024 Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage biopharmaceutical company focused on developing innovative treatments for cancer patients, reported promising preclinical imaging and therapeutic efficacy data for its MNPR-101 radiopharmaceutical program (Press release, Monopar Therapeutics, FEB 22, 2024, View Source [SID1234640395]). This novel first-in-class radiopharma program targets cancers expressing the urokinase plasminogen activator receptor (uPAR), which include a majority of all triple-negative breast, colorectal, and pancreatic cancers.

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MNPR-101 Conjugated to Imaging Radioisotope

Maximizing the dose delivered to the tumor relative to normal tissue is of paramount importance in radiopharmaceutical therapy. Figure 1 below shows the before and after optimization of MNPR-101-Zr, Monopar’s radiopharmaceutical imaging agent for advanced solid tumors expressing uPAR. Monopar’s in-house radiopharmaceutical development team was able to significantly increase tumor uptake of MNPR-101-Zr while minimizing uptake in healthy tissue, as shown in this preclinical positron emission tomography (PET) sequential imaging time-series. The high specificity and durable tumor uptake are evident in the After Optimization panel below.

Monopar recently announced it received Human Research Ethics Committee (HREC) clearance in Australia to commence a Phase 1 dosimetry clinical trial for MNPR-101-Zr in advanced cancer patients. "As we prepare to launch this clinical trial, we are encouraged by the significant, precise, and durable accumulation we are seeing in tumors and the corresponding therapeutic benefit in preclinical human tumor xenograft models," said Andrew Cittadine, Monopar’s Chief Operating Officer. "We are aiming to present these promising preclinical results at an upcoming scientific meeting."

On February 22, 2024 Notable Labs, Ltd. (Nasdaq: NTBL) ("Notable", "Notable Labs"), a clinical-stage therapeutics platform company developing a new class of cancer therapies based on its Predictive Precision Medicine Platform (PPMP), reported the advancement of its volasertib Phase 2 program utilizing PPMP to enrich the study population for clinical responders (Press release, Notable Labs, FEB 22, 2024, View Source [SID1234640394]). Notable is developing its lead drug asset volasertib with its proprietary PPMP for patients with relapsed/refractory acute myelogenous leukemia (r/r AML).

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"PPMP’s recently reported, 100% accurate prediction of fosciclopirox’s clinical trial outcome has allowed us to eliminate an entire 30-patient cohort from the planned volasertib program, and further validated our PPMP-guided development strategy to target responding patients, improve patient outcomes and reduce the risk, time, and cost of drug development," said Thomas Bock, M.D., Chief Executive Officer of Notable Labs.

"We in-licensed volasertib because of its robust clinical experience in Boehringer Ingelheim’s expansive Phases 1-3 program and our PPMP data that distinguished predicted volasertib-responders from predicted non-responders based on samples from patients with AML. We therefore believe that PPMP will focus volasertib’s development on clinically responding patients, boost its clinical response rate and enhance patient outcomes," continued Dr. Bock. "The open label design of our Phase 2 trial will enable us to provide frequent data updates, and initiate a subsequent Phase 3 trial at the earliest possibility."

Joseph Wagner, Ph.D., Chief Scientific Officer of Notable, added, "In our PPMP-guided Phase 2 trial, we are additionally leveraging important learnings from the extensive post-hoc analysis of the original Phase 2 and 3 trials. This analysis suggests that standardizing best supportive care and introducing body surface area-based dosing are likely to enhance patient responses and tolerability. We are going to include and evaluate these refinements in a small all-comers dose optimization prelude, expected to begin in Q2 2024 and be completed in Q4 2024, prior to enrolling PPMP-predicted responders."

Volasertib Phase 2 program: Summary of expected near-term clinical milestones

● Volasertib IND filing: Q1 2024
● Phase 2 program initiation: Q2 2024
● Prelude data on dose optimization: Q4 2024
● Enrollment of first PPMP-selected patient: Q4 2024

About Volasertib

Volasertib is a PLK-1 inhibitor with demonstrated activity in AML and other tumor types, including solid tumors, with significant unmet medical need. Building on the performance of volasertib on PPMP, an important and proprietary step during Notable’s targeted in-licensing strategy and decision making, Notable will utilize PPMP to predict volasertib-responsive patients prior to their treatment, with the goal of selectively enrolling and treating those predicted responders, increasing volasertib’s response rates and overall patient outcomes, and fast-tracking volasertib’s remaining clinical development in this patient population. Volasertib was originally developed and manufactured by Boehringer Ingelheim and previously granted breakthrough therapy designation by the FDA. Notable in-licensed volasertib and obtained exclusive worldwide development and commercialization rights, except for certain rare pediatric cancers.

About the Volasertib Phase 2 trial

Notable’s single-arm, open-label Phase 2 study of volasertib combined with decitabine in r/r AML patients is designed to achieve two objectives: i) to confirm the optimized tolerability profile suggested by volasertib’s Phase 3 post-hoc analysis through the introduction of body-surface area-based volasertib dosing and standardizing best supportive care, and ii) to evaluate the clinical impact of volasertib treatment on selectively enrolled r/r AML patients who are predicted to clinically respond, based on PPMP testing of their blood or bone marrow samples (PPMP-predicted responders). Parallel primary endpoints are i) a positive predicted response rate and ii) a per-protocol response assessment of complete remission and overall survival.

The Phase 2 program is designed to include a non-selective dose optimization prelude expected to enroll a small cohort of all-comers patients with r/r AML. This dose optimization prelude will evaluate the use of standardized best supportive care and body surface area-based dosing prior to beginning the prospective PPMP-based patient selection. Data on patient safety, tolerability, and efficacy, including overall safety, response and duration of response, will be evaluated.