On December 13, 2023 Amgen (NASDAQ:AMGN) reported that the U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review for the Company’s Biologics License Application (BLA) for tarlatamab (Press release, Amgen, DEC 13, 2023, View Source [SID1234638525]).

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Tarlatamab is a potential first-in-class, investigational delta-like ligand 3 (DLL3) targeting Bispecific T-cell Engager (BiTE) therapy for the treatment of adult patients with advanced small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.

"The FDA’s Priority Review designation for this application underscores the urgency to provide new treatment options for patients with advanced SCLC who have progressed following treatment with platinum-based chemotherapy," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "While first-line treatments often show strong responses, patients can experience aggressive recurrences and long-term survival remains a challenge.2,3 Unfortunately, for patients who relapse, there are limited treatment options, emphasizing the importance of bringing new therapies to this patient population with advanced disease."

The FDA grants Priority Review to applications for medicines that offer, if approved, significant improvements over available options or may provide a treatment option where no adequate therapy currently exists. Based on the Priority Review designation, the Prescription Drug User Fee Action (PDUFA) date for tarlatamab is June 12, 2024.

The BLA is based on the Phase 2 results from the DeLLphi-301 clinical trial that studied patients with advanced SCLC with disease progression on or after platinum-based chemotherapy. Results from the study were recently featured as part of a late-breaking presentation during the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and simultaneously published in the New England Journal of Medicine.4,5 The data presented demonstrated antitumor activity with a durable response and encouraging survival outcomes in previously treated SCLC. The safety profile was consistent with the Phase 1 trial.6

Tarlatamab is being investigated in multiple studies including DeLLphi-302, a Phase 1b study evaluating tarlatamab in combination with an anti-PD-1 therapy in second-line or later SCLC; DeLLphi-303, a Phase 1b study investigating tarlatamab in combination with standard of care therapies in first-line SCLC; DeLLphi-304, a randomized Phase 3 trial comparing tarlatamab monotherapy with standard of care chemotherapy in second-line treatment of SCLC that is enrolling patients; DeLLphi-306, a recently-initiated, randomized Phase 3 trial of tarlatamab following chemoradiotherapy in earlier settings of SCLC; and DeLLpro-300, a Phase 1b study of tarlatamab in de novo or treatment-emergent neuroendocrine prostate cancer.7 Amgen also plans to initiate an additional Phase 3 study of tarlatamab in first-line treatment of SCLC.

In October, tarlatamab was granted Breakthrough Therapy Designation by the FDA. The application is being reviewed by the FDA under the Project Orbis framework and Real Time Oncology Review (RTOR). Project Orbis is an initiative from the FDA Oncology Center of Excellence that provides a framework for concurrent submission of oncology products among certain countries.

About Small Cell Lung Cancer (SCLC)
SCLC is one of the most aggressive and devastating solid tumors with a median survival of approximately 12 months following initial therapy and a 7% five-year relative survival rate when all stages are combined.8-10 Of the more than 2.2 million patients diagnosed with lung cancer worldwide each year, SCLC comprises 15% of cases.11,1 Despite initial high response rates to platinum-based first-line chemotherapy, patients quickly relapse and require subsequent treatment options.1

About Tarlatamab
Tarlatamab is an investigational, targeted therapy engineered by Amgen researchers that brings a patient’s own T cells in close proximity to SCLC cells by binding both CD3 on T cells and DLL3 on SCLC cells. This results in the formation of a cytolytic synapse with lysis of the cancer cell.12,13 DLL3 represents an exciting therapeutic target for patients with SCLC, as approximately 85% to 96% of patients have expression of DLL3 on the cell surface of SCLC cells, with minimal expression in normal cells.6,14-16

About Tarlatamab Clinical Trials
Amgen’s robust tarlatamab development program includes the DeLLphi clinical trials, which evaluate tarlatamab as a monotherapy and as part of combination regimens in earlier stages of SCLC, and DeLLpro clinical trials, which evaluate tarlatamab in neuroendocrine prostate cancer.

In the Phase 1 DeLLphi-300 study, tarlatamab showed responses in 23.4% of patients with encouraging durability in heavily pre-treated patients with SCLC. In the Phase 2 DeLLphi-301 study, tarlatamab administered as 10 mg dose every two weeks demonstrated an objective response rate of 40% in patients with advanced SCLC who had failed two or more prior lines of treatment. In both DeLLphi-300 and DeLLphi-301, the most frequent treatment-related adverse events were cytokine release syndrome (CRS; 52-55%), pyrexia (31-37%), and dysgeusia (22-26%), which were primarily grade 1-2. Treatment discontinuation for adverse events occurred in 3-4% of patients in the two trials.5,6

For more information, please visit www.tarlatamabclinicaltrials.com.

About BiTE Technology
Bispecific T-cell Engager (BiTE) technology is a targeted immuno-oncology platform that is designed to engage patient’s own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. The BiTE immuno-oncology platform has the potential to treat different tumor types through tumor-specific antigens. The BiTE platform has a goal of leading to off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. Amgen is advancing multiple BiTE molecules across a broad range of hematologic malignancies and solid tumors, further investigating BiTE technology with the goal of enhancing patient experience and therapeutic potential. To learn more about BiTE technology, visit View Source

On December 13, 2023 Syntara (ASX:SNT) reported that it has commenced dosing in the final cohort of a phase 2 clinical trial studying its pan-LOX inhibitor SNT-5505 in patients with the bone marrow cancer myelofibrosis (Press release, Syntara, DEC 13, 2023, View Source [SID1234638506]). The trial was cleared to progress after FDA review of the protocol and data from the earlier cohort which demonstrated an excellent safety profile and encouraging signs of efficacy when used in patients who had failed on current standard of care.

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This additional cohort of the phase 2 trial MF-101 aims to demonstrate that SNT-5505, the lead asset in Syntara’s drug discovery pipeline, is safe and effective in myelofibrosis patients who are sub-optimally controlled on the market leading JAK inhibitor, ruxolitinib. Full recruitment of 15 patients is targeted for Q2 2024 from 19 clinical trial sites in Australia, South Korea, Taiwan and the USA. The open label study is expected to report interim data on 6 months of treatment in Q4 2024 and final data from 12 months treatment in Q2 2025.

Data previously announced by the company from the first cohort of MF-101 where SNT-5505 was used for 6 months in patients as a monotherapy was presented this week at the American Society of Haematology (ASH) (Free ASH Whitepaper) 2023 meeting in San Diego. The oral presentation was delivered in the New Therapeutic Frontiers session by Dr. Pankit Vachhani, Assistant Professor of Medicine & Medical Director of the Clinical Research Unit at the University of Alabama at Birmingham.

Commenting on the presentation, Dr Gabriela Hobbs, Assistant Professor, Medicine, Harvard Medical School & Clinical Director, Leukaemia, Massachusetts General Hospital said, "The data presented this week at ASH (Free ASH Whitepaper) demonstrated that when used as a monotherapy in patients who have failed on a JAK inhibitor, SNT-5505 comprehensively inhibits the LOX enzymes, is well tolerated, and in some patients led to improvements in fibrosis and blood counts, which are encouraging signs of efficacy. Treatments like SNT-5505 that are well tolerated and can improve/stabilize blood counts and fibrosis are needed. In particular, SNT-5505 in combination with JAK inhibitor therapy has the potential to enhance the impact of JAK inhibitor treatment on symptoms, which is a vital area for future research. I eagerly anticipate reviewing data from this next study cohort in 2024."

An effective pan-LOX inhibitor for myelofibrosis would open a market that is conservatively estimated at US$1 billion per annum.

Pharmaxis CEO Gary Phillips said, "This study that commenced recruitment today is crucial in establishing the place for SNT-5505 in the treatment regimen of myelofibrosis patients. The open label design enables us to assess the performance of SNT-5505 in real time and we are targeting a major interim data update at ASH (Free ASH Whitepaper) 2024 that will also trigger follow up discussions with the FDA on the pivotal registration study design and support ongoing discussions with strategic partners."

SNT-5505 is a pan-LOX inhibitor that has also demonstrated compelling pre-clinical data when used in combination with standard of care in other haematological malignancies such as myelodysplastic syndrome and solid tumours like those found in hepatocellular carcinoma and pancreatic cancer.

On December 12, 2023, Kiromic BioPharma, Inc. (the "Company") reported to have issued a 25% Senior Secured Convertible Promissory Note (the "Note") to an accredited investor (Filing, Kiromic, DEC 12, 2023, View Source [SID1234641113]). The Note has a principal amount of $2,000,000, bears interest at a rate of 25% per annum (the "Stated Rate") and matures on December 12, 2024 (the "Maturity Date"), on which the principal balance and accrued but unpaid interest under the Note shall be due and payable. The Stated Rate will increase to 27% per annum or the highest rate then allowed under applicable law (whichever is lower) upon occurrence of an event of default, including the failure by the Company to make payment of principal or interest due under the Note on the Maturity Date, and any commencement by the Company of a case under any applicable bankruptcy or insolvency laws.

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The Note is convertible into shares (the "Conversion Shares") of the Company’s common stock, par value $0.001 per share (the "Common Stock"), at an initial conversion price of $2.50 per share (the "Conversion Price"), subject to a beneficial ownership limitation equivalent to 9.99% (the "Beneficial Ownership Limitation").

The unpaid principal of and interest on the Note constitute unsubordinated obligations of the Company and are senior and preferred in right of payment to all subordinated indebtedness and equity securities of the Company outstanding as of the Issuance Date; provided, however, that the Company may incur or guarantee additional indebtedness after the Issuance Date, whether such indebtedness are senior, pari passu or junior to the obligations under the Note, which are secured by all of the Company’s right, title and interest, in and to, (i) all fixtures (as defined in the Uniform Commercial Code, the "UCC") and equipment (as defined in the UCC), and (ii) all of the Company’s intellectual property as specified in the Note, subject to certain exclusions as described in the Note.

The foregoing description of the Note is qualified in its entirety by reference to the full text of such Note, a copy of which is attached hereto as exhibit 10.1 and incorporated herein by reference.

On December 12, 2023 Molecure S.A. ("Molecure": WSE: MOC) a clinical stage biotechnology company developing first-in-class small molecule drug candidates that directly modulate unexplored protein and mRNA targets to treat multiple incurable diseases, reported in vitro that small molecule binding to the selected mRNA fragment inhibit the translation of the protein encoded by that mRNA (Press release, Molecure, DEC 12, 2023, View Source [SID1234640058]). Confirmation of the mechanism of stopping the pathological proteins translation in a dose dependent manner, represents a significant milestone in the development of the mRNA platform and has been one of the strategic goals of the Company during 2023-2025.

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‘The initial stage of scientific research in the mRNA platform involved identifying the structure of the mRNA region with high potential for binding small molecules (druggable regions). After confirming the functionality of this region, we conducted modeling of its tertiary structure, a necessary step to proceed to virtual screening. The binding of the best compounds to the mRNA fragment was confirmed using biophysical methods. The identified molecules, directly interacting with the mRNA fragment, demonstrated inhibition of the protein translation encoded by the given mRNA in a dose dependent manner. These results mark our anticipated Proof-of-Concept (PoC) for the first mRNA target in the platform. This big success achieved by our scientists validated of our ambitious approach for platform development. The next stage will involve evaluating the possibilities of continued preclinical and potentially clinical development of lead molecules optimized in this program. The company is also expanding its in-house expertise in identifying new mRNA regions that may serve as attractive therapeutic targets’ says Dr. Zbigniew Zasłona, Chief Scientific Officer, and Member of the Board at Molecure S.A.

‘We are proud to have achieved the in vitro Proof-of-Concept (PoC) for the first hit molecules developed in the mRNA platform. As the result of combining creativity, innovative approach, and the determination of our team in discovery of new molecules, leveraging strong in-house expertise in drug design using advanced digital methods. It confirms that we are among the global leaders in the field of mRNA-targeting small molecule drugs, a breakthrough technology with the potential to change the paradigm of treating many diseases, where the protein structure itself prevents direct interaction with small molecules (so-called undruggable targets). The development of the mRNA discovery platform, alongside our two clinical programs, is one of Molecure’s strategic priorities. Achieving the in vitro proof-of-concept this year, as outlined in our 2023-2025 strategy, is a significant milestone that we have reached and confirmed as planned. This will enable us to intensify partnering discussions and increase the likelihood of establishing commercially attractive collaborations with industry partners’ says Dr. Marcin Szumowski, CEO, and President of the Board at Molecure S.A.

The business model of the Company in the mRNA platform involves a hybrid approach. Molecure aims to develop its own proprietary projects targeting internally selected mRNA structures as well as provide services to external companies in the biopharmaceutical sector. These services involve validating mRNA fragments chosen by the client as therapeutic targets. This approach enables partnering and the generation of revenue as early as the optimization stage of active binders, i.e., after achieving in vitro Proof-of-Concept (PoC) for the relevant mRNA target.

Molecure is one of the few biotechnology companies globally developing small molecule drugs that directly interact with mRNA targets.

On December 12, 2023 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast cancers (mBC) harboring ESR1 mutations, reported the three poster presentations examining clinical data tied to Sermonix’s Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE) studies (Press release, Sermonix Pharmaceuticals, DEC 12, 2023, View Source [SID1234638576]). The presentations were initially shared last week at the 2023 San Antonio Breast Cancer Symposium (SABCS).

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"Secondary analysis of our ELAINE study results reveals reassuring pharmacokinetic data, further confidence in lasofoxifene’s ability to be effectively combined with abemaciclib, and a better understanding of the baseline genomic alterations found in patients with ESR1 mutations," said Dr. Paul Plourde, Sermonix vice president for clinical oncology development. "We are delighted to be actively screening and enrolling patients into our Phase 3 ELAINE-3 registrational trial at institutions across the U.S., and with the EU to closely follow."

One poster addressed pharmacokinetics (PK) of lasofoxifene as a monotherapy and in combination with Eli Lilly and Company’s CDK4/6 inhibitor abemaciclib (Verzenio). Key takeaways included:

PK data for lasofoxifene 5 mg/day were consistent with previous clinical trials, resulting in similar steady-state concentrations in patients across several studies.
Addition of abemaciclib to lasofoxifene did not appear to alter the PK of lasofoxifene in ELAINE-2 compared with monotherapy in ELAINE-1, suggesting little to no drug-drug interaction.
Abemaciclib concentrations in ELAINE-2 were consistent with previous monotherapy data, suggesting no impact of lasofoxifene on abemaciclib PK.
A second poster discussed baseline genomic alterations and the activity of lasofoxifene and abemaciclib during the ELAINE-2 study. Key results/conclusions included:

In 26 of the 29 patients (median age 60 years) enrolled, ESR1 mutations were identified at baseline by the Guardant360 CDx test. The profiling demonstrated that other genomic alterations are frequently detected concurrently with ESR1 mutations in the endocrine-resistant setting, in line with previous findings among patients with hormone receptor-positive mBC.
Co-alterations in ESR1 and other genes associated with treatment resistance did not appear to compromise the efficacy of lasofoxifene plus abemaciclib in ELAINE-2.
A third poster offered a trial-in-progress update on ELAINE-3, a 400-patient Phase 3 study assessing the efficacy and safety of lasofoxifene in combination with abemaciclib in treating locally advanced or ER+/HER2- mBC with an ESR1 mutation. ELAINE-3 enrollment is now underway.

To learn more about Sermonix Pharmaceuticals and lasofoxifene, visit View Source For more information about the ELAINE studies, visit View Source

About Lasofoxifene
Lasofoxifene is an investigational novel endocrine therapy in clinical development which has demonstrated robust target engagement as an ESR1 antagonist in the breast, particularly in the presence of ESR1 mutations. Lasofoxifene has demonstrated anti-tumor activity as monotherapy and in combination with a CDK4/6 inhibitor in Phase 2 studies and has unique tissue selectivity distinguishing it from other current and investigational endocrine therapies, with beneficial effects seen on vagina and bone in previous clinical studies. Lasofoxifene, which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ:LGND), has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a novel targeted and tissue selective oral endocrine therapy could, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer.