On December 13, 2023, Genprex, Inc. (the "Company") reported to have entered into an At The Market Offering Agreement (the "Agreement") with H.C. Wainwright & Co., LLC, serving as agent (the "Agent") with respect to an at-the-market offering program under which the Company may offer and sell, from time to time at its sole discretion, shares of its common stock, par value $0.001 per share (the "Common Stock"), having an aggregate offering price of up to $25.0 million (the "Shares") through the Agent (the "Offering"). Any Shares offered and sold in the Offering will be issued pursuant to the Company’s shelf Registration Statement on Form S-3 (File No. 333-271386) filed with the Securities and Exchange Commission (the "SEC") on April 21, 2023, which was declared effective on June 9, 2023, the related prospectus contained therein, and the prospectus supplement relating to the Offering to be filed with the SEC on December 13, 2023 and any applicable additional prospectus supplements related to the Offering that form a part of the Registration Statement (Filing, 8-K, Genprex, DEC 13, 2023, View Source [SID1234638528]).

The Agent may sell the Shares by any method permitted by law deemed to be an "at the market offering" as defined in Rule 415 of the Securities Act of 1933, as amended, including, without limitation, sales made through The Nasdaq Capital Market ("Nasdaq") or on any other existing trading market for the Common Stock. The Agent will use commercially reasonable efforts to sell the Shares from time to time consistent with its normal sales practices and applicable federal rules, regulations and Nasdaq rules, based upon instructions from the Company (including any price, time or size limits or other customary parameters or conditions the Company may impose). The Company will pay the Agent a commission equal to three percent (3%) of the gross sales proceeds of any Shares sold through the Agent under the Agreement, and also has provided the Agent with customary indemnification and contribution rights.

The Agent is not required to sell any specific number or dollar amount of securities, but will use commercially reasonable efforts to sell, on behalf of the Company, all of the shares of common stock requested to be sold by the Company, consistent with its normal trading and sales practices, on mutually agreed terms between the Agent and the Company. There is no arrangement for funds to be received in any escrow, trust or similar arrangement.

The foregoing description of the Agreement is not complete and is qualified in its entirety by reference to the full text of the Agreement, a copy of which is filed herewith as Exhibit 1.1 to this Current Report on Form 8-K and is incorporated herein by reference. A copy of the opinion of Lowenstein Sandler LLP relating to the legality of the issuance and sale of the shares in the Offering is attached as Exhibit 5.1 hereto.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the securities discussed herein, nor shall there be any offer, solicitation, or sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

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On December 13, 2023 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, reported that the Company granted a non-qualified stock option to one newly-hired employee to purchase a total of 350,000 shares of the Company’s common stock at an exercise price per share of $2.28, which was the closing price per share of the Company’s common stock as reported by NASDAQ on the grant effective date of December 11, 2023 (Press release, Fate Therapeutics, DEC 13, 2023, View Source [SID1234638527]). The option was approved by the Compensation Committee of the Company’s Board of Directors and granted under the Company’s Amended and Restated Inducement Equity Plan as an inducement material to the new employee entering into employment with the Company in accordance with Nasdaq Listing Rule 5635(c)(4). The option vests over four years, with 25% vesting on the one-year anniversary of the grant date and the remaining 75% percent vesting in approximately equal monthly installments over the following thirty-six months, subject to the employee being continuously employed by the Company through each vesting date.

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On December 13, 2023 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with genetically defined cancers, reported topline results from the dose escalation portion of the Phase 1 clinical trial of BDTX-1535 in patients with recurrent glioblastoma (GBM) who expressed epidermal growth factor receptor (EGFR) alterations at the time of their initial diagnosis (Press release, Black Diamond Therapeutics, DEC 13, 2023, View Source [SID1234638526]). BDTX-1535, a fourth-generation, brain-penetrant, covalent EGFR inhibitor, is under investigation in a Phase 1 clinical trial for the treatment of patients with non-small cell lung cancer (NSCLC) or GBM.

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"These initial results in patients with recurrent GBM are encouraging, as there are no approved therapies available for those who progress following initial treatment, and there is strong rationale for a brain penetrant, covalent EGFR inhibitor such as BDTX-1535 to have a meaningful impact in earlier lines of therapy," said Patrick Wen, M.D., Director of The Center for Neuro-Oncology at Dana-Farber Cancer Institute.

Clinical data as of November 2023 reflect 27 patients with recurrent GBM who received a range of doses spanning 15mg to 400mg once daily (QD) in the dose escalation cohort. Combined pharmacokinetic (PK) and safety data from these 27 patients with GBM and 27 patients with NSCLC were previously presented on October 14, 2023 at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper). No new safety signals were observed; adverse events were consistent with the EGFR tyrosine kinase inhibitor (TKIs) class of drugs, including primarily Grade 1 and 2 diarrhea and rash. Patients with NSCLC dosed at 100mg QD or greater demonstrated confirmed partial responses in lung lesions and CNS metastases.

Key enrollment and inclusion factors

Of the 27 patients with recurrent GBM, 22 were started at or escalated to a dose of 100mg QD or greater and reached at least one post baseline tumor assessment.
Patients were heavily pretreated, with a median of 2 prior lines of therapy (range 1-4). All patients except one had received prior temozolomide. Other prior treatments included chemotherapy, bevacizumab, checkpoint inhibitors or investigational agents.
Patients were required to have EGFR alterations at the time of diagnosis, but EGFR status was not known at time of treatment with BDTX-1535 as biopsies are not commonly performed for recurrent disease.
Key results

Of the 22 patients evaluable for efficacy, 3 patients were on therapy longer than 10 months, 1 patient longer than 6 months, and 5 patients longer than 4 months. Historical progression-free survival (PFS) in this population is in the range of 2-4 months.
The patient on therapy the longest remains on BDTX-1535 at 100mg QD for over 15 months with prolonged disease stabilization. This patient had previously progressed after 3 months of temozolomide treatment.
Of the 19 patients with measurable disease by Response Assessment in Neuro-Oncology (RANO) criteria, 1 patient achieved a confirmed partial response (PR) and 8 patients experienced stable disease (SD). The patient with the PR stayed on treatment for longer than 4 months at 200 mg QD.
Black Diamond plans to submit results from the dose escalation GBM cohort for presentation at a medical meeting in the second quarter of 2024. Enrollment is ongoing in a "window of opportunity" clinical trial of BDTX-1535 in second-line patients with high-grade glioma. The trial (NCT06072586) is sponsored by the Ivy Brain Tumor Center in Phoenix, Arizona and is enrolling patients prior to a planned resection in order to assess PK and pharmacodynamics (PD) in brain tissue. Patients achieving adequate drug levels in the gadolinium non-enhancing regions of the tumor will continue with treatment following surgery. The trial will enroll up to 22 patients, and clinical data is expected in the second quarter of 2024.

"We believe the ‘window of opportunity’ trial of BDTX-1535 will provide valuable information on both drug levels in the brain and clinical activity in second-line patients, and will inform potential next steps in our development program," said Sergey Yurasov, M.D., Ph.D., Chief Medical Officer of Black Diamond Therapeutics. "More than half of all newly diagnosed GBM patients express an altered form of EGFR, and preclinical data demonstrate BDTX-1535 potently inhibits this spectrum of alterations. Therefore, BDTX-1535 may be optimally suited to benefit first-line patients."

About BDTX-1535

BDTX-1535 is an oral, brain-penetrant MasterKey inhibitor of oncogenic epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC), including families of non-classical driver mutations (e.g., L747P, L718Q), acquired resistance C797S mutation, and complex mutations. BDTX-1535 is a fourth generation TKI that potently inhibits, based on preclinical data, more than 50 oncogenic EGFR mutations expressed across a diverse group of patients with NSCLC in multiple lines of therapy. Based on preclinical data, BDTX-1535 also inhibits EGFR extracellular domain mutations and alterations commonly expressed in glioblastoma (GBM) and avoids paradoxical activation observed with earlier generation reversible TKIs. Dose escalation of BDTX-1535 in patients with GBM is complete and dose expansion is currently ongoing in patients with NSCLC (NCT05256290).

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.