On March 26, 2024 Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that the U.S. Food and Drug Administration (FDA) has granted Priority Review for its New Drug Application (NDA) for revumenib, the Company’s first-in-class menin inhibitor, for the treatment of adult and pediatric relapsed or refractory (R/R) KMT2A-rearranged (KMT2Ar) acute leukemia (Press release, Syndax, MAR 26, 2024, View Source [SID1234641453]). The NDA filing is being reviewed under the FDA’s Real-Time Oncology Review Program (RTOR) and has been assigned a Prescription Drug User Fee Act (PDUFA) target action date of September 26, 2024. RTOR allows for a more efficient review and close engagement between the sponsor and the FDA throughout the submission process, which historically has led to earlier approvals.

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 receipt of Priority Review for the revumenib NDA filing is a significant milestone as we transition to a leading commercial-stage oncology company with the planned launches of two first- and best-in class drugs in 2024," said Michael A. Metzger, Chief Executive Officer. "With two regulatory filings now under FDA Priority Review, our team is focused on commercial preparations to enable Syndax’s continued success as we enter this next stage of growth."

The NDA submission is supported by positive data from the pivotal AUGMENT-101 trial of revumenib in adult and pediatric patients with KMT2Ar acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). As previously reported, the trial met its primary endpoint at the protocol-defined interim analysis with a complete remission (CR) or a CR with partial hematological recovery (CRh) rate of 23% (13/57; 95% confidence interval [CI]: [12.7, 35.8, one-sided p-value = 0.0036]) among the 57 efficacy evaluable patients in the pooled KMT2Ar acute leukemia population. 70% of patients who achieved a CR/CRh and were assessed for minimal residual disease (MRD) were MRD negative. Additionally, 63% (36/57) of the efficacy-evaluable patients achieved an overall response, 39% (14/36) of whom underwent hematopoietic stem cell transplant (HSCT), with 50% (7/14) restarting revumenib as post-transplant maintenance at the time of the data cutoff.

About Revumenib

Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged, also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and NPM1-mutant AML. Positive topline results from the Phase 2 AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint were presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and data from the Phase 1 portion of AUGMENT-101 in acute leukemia was published in Nature. Revumenib was granted Orphan Drug Designation by the FDA and European Commission for the treatment of patients with AML and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib was granted Breakthrough Therapy Designation (BTD) by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.

About Real-Time Oncology Review (RTOR)

RTOR provides a more efficient review process for oncology drugs to ensure that safe and effective treatments are available to patients as early as possible, while improving review quality and engaging in early iterative communication with the applicant. Specifically, it allows for close engagement between the sponsor and the FDA throughout the submission process and it enables the FDA to review individual sections of modules of a drug application rather than requiring the submission of complete modules or a complete application prior to initiating review. Additional information about RTOR can be found at: View Source

On March 26, 2024 Aptamer Sciences Inc. (KOSDAQ, 291650) reported the filing of an Investigational New Drug (IND) application for the phase 1 clinical trial of AST-201 with the Korean Ministry of Food and Drug Safety on March 12th, 2024 (Press release, Aptamer Sciences, MAR 26, 2024, View Source [SID1234641473]).

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!

AST-201, the company’s pioneering candidate in its pipeline, is an ApDCTM (Aptamer-Drug Conjugate) designed to target GPC3 protein, which exhibits high expression levels in specific cancer cells, notably liver cancer. It comprises gemcitabine as the payload and an aptamer that selectively binds to GPC3 protein. Gemcitabine, a proven systemic anticancer agent, is widely utilized in treating various cancers, including ovarian, breast, non-small cell lung, and pancreatic cancer. The choice of gemcitabine as the payload was deliberate, owing to its moderate toxicity profile, particularly suitable for liver targeting, given the organ’s susceptibility to drug toxicity. Additionally, gemcitabine’s nature as a DNA analogue facilitates its synthesis within the aptamer DNA sequence. The company’s strategic focus on liver cancer addresses significant unmet medical needs, as evidenced by AST-201’s superior efficacy over sorafenib in animal models and its synergistic effect when co-administered with anti-PD-1 therapy.

Liver cancer poses a significant health challenge, particularly in East Asia, with a dismal survival rate. While combination therapies such as atezolizumab and bevacizumab have emerged as standard treatments for advanced liver cancer, recent findings published in Nature Medicine suggest their limited efficacy in certain liver cancer populations with high GPC3 expression levels, highlighting substantial unmet medical needs. In this context, AST-201 offers a promising therapeutic approach by specifically targeting GPC3.

The planned phase 1 trial seeks to evaluate the safety, pharmacokinetic profile, and preliminary efficacy of AST-201 in patients with GPC3-positive advanced solid tumors. Notably, Dr. Hong Jae Chon from CHA Bundang Medical Center, a prominent medical oncologist in South Korea, will serve as the coordinating investigator. The trial will be conducted across four hospitals, including CHA Bundang Medical Center, Samsung Medical Center, Severance Hospital, and the National Cancer Center in South Korea.

Dr. Chon remarked, "GPC3 has garnered considerable attention in liver cancer therapeutic development among biopharmaceutical companies," expressing optimism that "AST-201 may emerge as a novel treatment option for liver cancer patients."

Aptamer Sciences Inc. aims to showcase the clinical benefits of AST-201 and the technological value of its ApDCTM platform through this trial. Moreover, the company anticipates that this milestone will propel its research and development efforts, enhancing the competitiveness of its subsequent hemato-oncology pipeline products, including AST-202 targeting CD25, ApRC (Aptamer Radioligand Conjugate), ApIS (Aptamer Immune Stimulator Conjugate), and so on.

Dr. Dong-il Han, CEO of Aptamer Sciences Inc., emphasized, "Since the second aptamer drug Izervay approved by FDA last year, aptamer technology has garnered significant attention in the pharmaceutical market," highlighting, "The AST-201 clinical trial will showcase the technological capabilities of the ApDCTM platform and expedite ongoing technology transfer discussion with multiple partners. This milestone underscores Aptamer Sciences Inc.’s commitment to advancing innovative therapies and addressing critical unmet needs in oncology."

Fig 1. AST-201 structure (Among the sequence of GPC3 aptamer, the payload of gemcitabine is conjugated as the part of sequence.)

Fig 2. AST-201 mechanism of action

1. AST-201 targets and binds to the GPC3 protein located on the surface of cancer cells.

2. The drug undergoes internalization into the cancer cell by endocytosis.

3. After the lysosomal degradation, gemcitabine monophosphate (dFdCMP), the active form of gemcitabine, is released within the cell leading to programmed cell death of the tumor cell (apoptosis).

On March 26, 2024 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a commercial stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases, reported its financial results for the year ended December 31, 2023, and provided recent corporate and portfolio updates (Press release, BioLineRx, MAR 26, 2024, https://ir.biolinerx.com/news-releases/news-release-details/biolinerx-reports-2023-financial-results-and-recent-corporate [SID1234641438]).

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!

"Following FDA approval of APHEXDA in September, physicians and transplant centers have been very receptive to the value of our strong clinical data, and our commercial team has made substantial progress establishing relationships with transplant centers across the country," said Philip Serlin, Chief Executive Officer of BioLineRx. "This year will continue to be primarily a foundational period for the commercialization of APHEXDA. We are seeing substantial progress on Pharmacy & Therapeutics committee approvals — the first step toward center adoption — and are actively supporting centers as they build usage protocols and treat their first patients. Initial feedback on patient experiences has been positive, and we are already seeing repeat purchases. Notably, we have achieved payer coverage representing approximately 95% of covered lives in the U.S. to date, which we believe reflects the value that APHEXDA offers to payers and patients alike, particularly its ability to mobilize the targeted number of stem cells in fewer apheresis sessions.

"Additionally, through a clinical collaboration with Washington University, we are actively evaluating the potential of motixafortide to support gene therapy for patients with sickle cell disease, a treatment process that requires significant quantities of hematopoietic stem cells. We anticipate data from this proof-of-concept Phase 1 study in patients with sickle cell disease in the second half of this year.

"At the same time, we are making significant progress advancing clinical programs evaluating motixafortide in pancreatic cancer, which if ultimately approved in combination with PD-1 inhibitors, would serve a much larger patient population and provide confidence for expanding into additional solid tumors. In pancreatic cancer, our enthusiasm is bolstered by the compelling data presented last fall from the single-arm pilot phase of the Phase 2b trial sponsored by Columbia University. The first patient has now been dosed in the randomized Phase 2b portion of that study, and we are also working with Gloria Biosciences on the design and execution of a similar randomized Phase 2b combination trial of motixafortide and zimberelimab in pancreatic cancer in China.

"Our vision of bringing a best-in-class stem cell mobilization agent to market, as well as advancing development in pancreatic cancer and other solid tumor areas with major unmet needs, is being actively realized. We look forward to the exciting, continued execution progress that our commercial and development teams will make this year," Mr. Serlin concluded.

Corporate Updates

Launched APHEXDA (motixafortide) in the U.S.
Announced closing of exclusive license agreement that includes development and commercialization rights to motixafortide across all indications in the Asia region, as well as a strategic equity investment
Strengthened motixafortide intellectual property estate with notice of allowance for U.S. patent covering method of manufacturing motixafortide suitable for large scale production; the patent supplements existing Orphan Drug Designation in the U.S. and Europe for the treatment of pancreatic cancer, as well as Orphan Drug market exclusivity for autologous stem cell mobilization in multiple myeloma patients in the U.S. following last year’s FDA approval of APHEXDA
APHEXDA Launch Updates

Reported positive coverage decisions by payers representing ~95% of all covered lives in the U.S.
Received inclusion of APHEXDA in the National Comprehensive Cancer Network (NCCN) guidelines for Hematopoietic Cell Transplantation
Achieved "on formulary" status for APHEXDA within targeted top 80 transplantation centers (which perform 85% of all U.S. transplants) managing ~20% of stem cell transplant procedures at these institutions; anticipate similar on formulary status of ~35% at end of Q2 2024 and ~60% at year-end 2024
Received Healthcare Common Procedure Coding System (HCPCS) J-Code to facilitate Medicare reimbursement for APHEXDA to transplant centers treating Medicare beneficiaries
Clinical Portfolio Updates

Motixafortide (selective inhibitor of CXCR4 chemokine receptor)

Multiple Myeloma

Presented posters at both the American Society of Hematology (ASH) (Free ASH Whitepaper) 65th Annual Meeting on December 10, 2023, and the 2024 Tandem Meetings on February 21-24, 2024. The posters reviewed combination premedication benefits in the Phase 3 GENESIS trial, extended PD effect of elevated CD34+ cells in peripheral blood, and a post-hoc subgroup analysis of impaired HSC mobilization patients that demonstrated a consistent benefit of motixafortide + G-CSF over placebo + G-CSF mobilization for all patients
Supported collaboration partner Gloria Biosciences with stem cell mobilization bridging study IND filing in February with the Center for Drug Evaluation of the National Medical Products Administration in China. Anticipate regulatory action in May 2024 and initiation of pivotal clinical trial in 2H 2024
Pancreatic Ductal Adenocarcinoma (mPDAC)

Announced first patient dosed in a randomized, investigator-initiated Phase 2b clinical trial in collaboration with Columbia University assessing motixafortide in combination with the PD-1 inhibitor cemiplimab and standard-of-care chemotherapy as first-line treatment in patients with metastatic pancreatic cancer
Advanced plans with collaboration partner Gloria Biosciences on a Phase 2b randomized clinical trial in China assessing motixafortide in combination with the PD-1 inhibitor zimberelimab and standard-of-care chemotherapy as first-line treatment in patients with metastatic pancreatic cancer. Anticipate clinical trial initiation in 2025
Sickle Cell Disease (SCD) & Gene Therapy

Continued to enroll patients into a clinical trial in collaboration with Washington University School of Medicine in St. Louis to evaluate motixafortide as monotherapy and in combination with natalizumab for stem cell mobilization for gene therapies in sickle cell disease. Anticipate data in 2H 2024
Financial Results for Year Ended December 31, 2023

Total revenues for the year ended December 31, 2023, were $4.8 million, compared to no revenues for the year ended December 31, 2022. Revenues in 2023 (all of which were recorded in the fourth quarter) primarily reflect a portion of the upfront payment from the Gloria Biosciences license agreement, of which $4.6 million was recognized in 2023, as well as $0.2 million of revenues from product sales of APHEXDA in the U.S.
Cost of revenues for the year ended December 31, 2023, amounted to $3.7 million, compared to no cost of revenues for the year ended December 31, 2022. The cost of revenues in 2023 (all of which was recorded in the fourth quarter) primarily reflects a $3.0 million sub-license fee to the upstream licensor of motixafortide payable on closing of the exclusive license agreement in Asia, as well as amortization of an intangible asset in respect of these license revenues in the amount of $0.5 million. Cost of product sales were insignificant, representing approximately 6% of related sales.
Research and development expenses for the year ended December 31, 2023, were $12.5 million, compared to $17.6 million for the year ended December 31, 2022. The decrease resulted primarily from lower expenses related to motixafortide NDA supporting activities, as well as lower expenses associated with completion of the AGI-134 study
Sales and marketing expenses for the year ended December 31, 2023, were $25.3 million, compared to $6.5 million for the year ended December 31, 2022. The increase resulted primarily from the ramp-up of pre-commercialization and commercialization activities related to motixafortide
General and administrative expenses for the year ended December 31, 2023, were $6.3 million, compared to $5.1 million for the year ended December 31, 2022. The increase resulted primarily from an increase in payroll and related expenses associated with a small headcount increase during the 2022 period, as well as an increase in professional services and legal expenses
Non-operating expenses for the year ended December 31, 2023, were $10.8 million, compared to non-operating income of $5.7 million for the year ended December 31, 2022. Non-operating expenses and income primarily relate to the non-cash revaluation of outstanding warrants resulting from changes in the company’s share price during the respective periods
Net loss for the year ended December 31, 2023 was $60.6 million, compared to $25.0 million for the year ended December 31, 2022. The net loss for 2023 included $17.8 million in non-cash expenses, specifically an expense of $11.1 million for the revaluation of warrants and a one-time $6.7 million impairment of intangible assets associated with discontinuation of the AGI-134 development program. The net loss for 2022 included $6.4 million in non-cash income specifically related to the revaluation of warrants.
As of December 31, 2023, the Company had cash, cash equivalents, and short-term bank deposits of $43.0 million. The Company anticipates that this amount and other available resources, including amounts available under a debt facility with Kreos Capital, will be sufficient to fund operations, as currently planned, into 2025
A copy of the Company’s annual report on Form 20-F for the year ended December 31, 2023 has been filed with the U.S. Securities and Exchange Commission at View Source and posted on the Company’s investor relations website at View Source Company will deliver a hard copy of its annual report, including its complete audited consolidated financial statements, free of charge, to its shareholders upon request at [email protected].

Conference Call and Webcast Information

To access the conference call, please dial +1-888-281-1167 from the U.S. or +972-3-918-0685 internationally. A live webcast and a replay of the call can be accessed through the event page on the Company’s website. Please allow extra time prior to the call to visit the site and download any necessary software to listen to the live broadcast. The call replay will be available approximately two hours after completion of the live conference call. A dial-in replay of the call will be available until March 28, 2024; please dial +1-888-295-2634 from the US or +972-3-925-5904 internationally.

On March 26, 2024 Volastra Therapeutics, a clinical-stage biotechnology company, reported partnerships with Microsoft, Function Oncology and Tailor Bio with the goal of broadening the potential of its evolving therapeutics pipeline across a large number of tumor types through identification of predictive biomarkers (Press release, Volastra Therapeutics, MAR 26, 2024, View Source [SID1234641454]).

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!

Volastra leads the field in development of therapeutics that target chromosomal instability (CIN), a key characteristic of cancer associated with accelerated disease progression, increased resistance to therapies, and shortened patient survival. While CIN is a hallmark of cancer, levels of CIN vary widely across tumor types from being nearly ubiquitous in some to only partially present in others.

Volastra’s two KIF18A inhibitors are in parallel Phase 1 clinical trials treating tumor types with near-universally high levels of CIN. Significant potential remains in many other tumor types, for which a biomarker-defined approach may be able to identify subsets of patients most likely to benefit from treatment.

"Predictive biomarkers can help us expand the reach of our therapies to as many patients as possible," said Charles Hugh-Jones, M.D., FRCP, CEO at Volastra. "By leveraging the diverse expertise of our partners, we believe we can achieve this even in cancers with heterogenous levels of CIN."

Volastra has collaborated with Microsoft Research since 2020 to develop image-based artificial intelligence (AI) models that quantify CIN in patient samples.

"Our collaboration has shown extraordinary progress in creating AI techniques to identify visual hallmarks of CIN with high levels of accuracy, a process that is incredibly difficult and expensive for humans to do alone," commented Jonathan Carlson, Ph.D., Managing Director, Microsoft Research Heath Futures. "We are thrilled to continue to combine our research expertise with Volastra’s so they may amplify their impact and reach more patients."

This novel visual approach will now be complemented by the unique and distinct expertise of Function Oncology and Tailor Bio, both recognized leaders in precision medicine.

"Function’s collaboration with Volastra integrates our unique CRISPR platform to decipher patient-specific drug target vulnerabilities," said Srinath Sampath, M.D., Ph.D., M.Phil., co-founder and CEO of Function Oncology. "Our platform allows us to reach ground-state genetic truth about target dependence in cancer and beyond, and we look forward to applying this technology to Volastra’s clinical programs."

Jason Yip, MBA, co-founder and CEO of Tailor Bio commented, "Our latest Nature publication demonstrated the remarkable potential for genomic CIN signatures to quantify unique aspects of chromosomal instability. We are excited to apply our proprietary precision medicine platform to clinical trials in the rapidly advancing field of KIF18A inhibition."

On March 26, 2024 Amplia Therapeutics Limited (ASX: ATX), ("Amplia" or the "Company"), reported an update on its Phase 1b/2a trial (the ACCENT trial) of narmafotinib in combination with standard-of-care chemotherapy gemcitabine and Abraxane in first-line patients with advanced pancreatic cancer (Press release, Amplia Therapeutics, MAR 26, 2024, View Source [SID1234641474]). Narmafotinib is the company’s best-in-class inhibitor of the protein FAK, a drug target gaining increasing attention in the treatment of solid tumours.

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!

Completion of the Phase 1b stage of the trial was announced in November 2023.

• Fourteen (14) patients were dosed over three dose levels,
• A safe and well-tolerated dose of 400 mg narmafotinib once-a-day was identified that provided the drug levels to significantly inhibit FAK.
• Of these fourteen patients seven (7) patients remained on trial for >6 months, with two (2) patients being on trial for more than 10 months. By contrast, the median progression free survival for advanced pancreatic cancer patients treated with gemcitabine and Abraxane alone is 5.5 months.
• Six (6) patients have now recorded a partial response as best response, with the remaining eight (8) recording stable disease.
• These response rates are substantially higher than predicted from historical studies of gemcitabine and Abraxane treatment alone.
• Three (3) patients remain on trial from the Phase 1b cohort. The Phase 2a trial will initially enrol 26 patients over the coming months. Recruitment into this next stage of the trial is progressing well recruiting patients through six trial sites in Australia and five trial sites in South Korea.
• Currently eleven patients have now been recruited.
• Seven patients in Australia and four patients in Korea.

An interim analysis of efficacy will then be conducted around Q3 2024. An efficacy assessmentshowing six or more partial or complete responses out of the 26 patients will be sufficient to continue the trial. An additional 24 patients will then be enrolled to give a total of 50 patients.

Amplia CEO and MD Dr Chris Burns commented: "The clinical responses we are seeing in patientsfrom the Phase 1b stage is very promising. The duration on trial, given the aggressiveness of the disease inthese patients, is also extremely encouraging. As reported at the end of our Phase 1b trial, the drug safety and tolerability also appears to be very acceptable for this patient group. We look forward to reporting on further data from the trial as the Phase 2a patients are assessed."

About the ACCENT Trial

The protocol for the ACCENT trial is entitled ‘A Phase 1b/2a, Multicentre, Open Label Study of the Pharmacokinetics, Safety and Efficacy of AMP945 in Combination with Nab-paclitaxel and Gemcitabine in Pancreatic Cancer Patients’. The trial is a single-arm open label study conducted in two stages. The first stage (Phase 1b) determined an optimal dose of AMP945 by assessing the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of AMP945 when dosed in combination with gemcitabine and Abraxane in first-line patients with advanced pancreatic cancer.

This second stage (Phase 2a), of the trial is designed to assess efficacy in combination with gemcitabine and Abraxane. The primary endpoints are Objective Response Rate (ORR) and Duration on Trial (DOT) with secondary endpoints being Progression Free Survival (PFS) and Overall Survival (OS). Safety and tolerability will continue to be assessed.

More information about the ACCENT trial, including a list of participating sites, can be found via the Amplia Therapeutics website and at ClinicalTrials.gov under the identifier NCT05355298.

The Company will provide further updates on the trial as recruitment proceeds.