On July 15, 2024 Sumitomo Pharma America, Inc. (SMPA) reported that the U.S. Food and Drug Administration (FDA) granted Fast Track designation to DSP-5336 for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) with a KMT2A rearrangement, also known as, mixed lineage leukemia rearrangement (MLLr) or nucleophosmin mutation (NPM1m) (Press release, Sumitomo Dainippon Pharma, JUL 15, 2024, View Source [SID1234644876]). DSP-5336 is an investigational small molecule inhibitor of the menin and mixed-lineage leukemia (MLL) protein interaction, which plays key roles in gene expression and protein interactions involved in many biological pathways, including cell growth, cell cycle, genomic stability, and hematopoiesis.1,2,3

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FDA Fast Track Designation is granted to investigational therapies being developed to treat serious or life-threatening conditions that demonstrate the potential to address unmet medical needs.

"For patients and families facing a diagnosis of relapsed or refractory acute myeloid leukemia, significant unmet medical needs remain – and we share in their urgency to identify and advance new treatment pathways," said Tsutomu Nakagawa, Ph.D, President and Chief Executive Officer of SMPA. "We are encouraged by FDA’s decision and look forward to working closely with the agency as we continue our clinical development of DSP-5336."

Updated data from the ongoing open-label, dose escalation and optimization portion of the Phase 1/2 study for DSP-5336 were presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress, building on preliminary data presented at the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Objective response was observed in 57% (12/21) of patients, which included responses in patients with both Nucleophosmin 1 (NPM1) mutation and KMT2A (MLL) rearrangement. The proportion with complete remission or complete remission with partial hematologic recovery (CR/CRh) was 24% (5/21 patients).

To date, DSP-5336 remains well-tolerated with no dose limiting toxicity (DLT) observed and no significant cardiac signal nor treatment-related discontinuations or deaths. No significant drug-drug interactions with azoles have been identified and repeat dosing results in minimal to no pharmacokinetic accumulation. Importantly, no differentiation syndrome (DS) prophylaxis was needed, and the three cases of DS reported (5%) were manageable and did not result in intensive care unit (ICU) stays or discontinuation of DSP-5336.

"Management of AML continues to be challenging with limited options for which there are currently no approved targeted therapies to treat AML with KMT2A (MLL) rearrangements or NPM1 mutations, leaving a serious unmet medical need," said Jatin Shah, M.D., Chief Medical Officer – Oncology at SMPA. "DSP-5336 has shown promising clinical activity, and menin inhibitors have tremendous potential to impact the outcomes of these types of acute leukemia. We are excited by these early results and FDA Fast Track Designation, and look forward to working closely with the agency and our collaborators to rapidly advance this program with the goal of providing a well-tolerated and effective targeted treatment option for patients with relapsed or refractory acute myeloid leukemia."

Leukemia is a type of cancer that forms in blood-forming tissue, characterized by the uncontrolled growth of blood cells, usually white blood cells, in the bone marrow. Acute leukemia, a form of leukemia, requires immediate treatment as blood cells multiply rapidly leading to a sudden onset of symptoms.4 Approximately 30% of AML patients have NPM1 mutations6 and 5-10% of AML patients have KMT2A (MLL) rearrangements.5

About DSP-5336
DSP-5336 is an investigational small molecule inhibitor of the menin and mixed-lineage leukemia (MLL) protein interaction. Menin is a scaffold nuclear protein which plays key roles in gene expression and protein interactions involved in many biological pathways, including cell growth, cell cycle, genomic stability, and hematopoiesis.1,2 In preclinical studies, DSP-5336 has shown selective growth inhibition in human acute leukemia cell lines with KMT2A (MLL) rearrangements or NPM1 mutations.1,3 DSP-5336 reduced the expression of the leukemia-associated genes HOXA9 and MEIS1, and increased the expression of the differentiation gene CD11b in human acute leukemia cell lines with MLL rearrangements and NPM1 mutation.7,8 The safety and efficacy of DSP-5336 is currently being clinically evaluated in a Phase 1/2 dose escalation/dose expansion study in patients with relapsed or refractory acute leukemia (NCT04988555). The FDA granted Orphan Drug Designation for DSP-5336 for the indication of acute myeloid leukemia in June 2022. The FDA granted Fast Track Designation for DSP-5336 for the indication of relapsed or refractory acute myeloid leukemia with MLLr or NPM1m in June 2024.

On July 15, 2024 Mabwell (688062.SH), an innovative biopharmaceutical company with entire industry chain, reported its novel Nectin-4 targeting ADC (R&D code: 9MW2821) has been approved by the NMPA to enter Phase II clinical trial as monotherapy or in combination with a PD-1 inhibitor for the treatment of triple-negative breast cancer (TNBC) (Press release, Mabwell Biotech, JUL 15, 2024, View Source [SID1234644875]).

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The Phase II clinical trial recently approved aims to evaluate the efficacy and safety of 9MW2821 as monotherapy or in combination with a PD-1 inhibitor in patients with locally advanced or metastatic TNBC. The study includes two cohorts: Cohort A will enroll patients with locally advanced or metastatic TNBC who have previously received taxane/anthracycline-based chemotherapy and topoisomerase inhibitor based antibody-drug conjugate treatment, and will receive 9MW2821 monotherapy; Cohort B will enroll patients with locally advanced or metastatic TNBC who have not previously received systemic therapy, and will receive a combination treatment of 9MW2821 and a PD-1 inhibitor.

Clinical results previously presented at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting showed that among the 20 patients with locally advanced or metastatic TNBC treated by 9MW2821 and evaluable for efficacy assessment, the objective response rate (ORR) and disease control rate (DCR) were 50.0% and 80.0% respectively. The median progression-free survival (mPFS) was 5.9 months, and the median overall survival (mOS) was not yet reached, with one patient achieved complete response (CR) and had been in CR for 20 months and is currently sustained to be CR. Additionally, 9MW2821 has recently been granted Fast Track Designation (FTD) by the U.S. Food and Drug Administration (FDA) for the treatment of locally advanced or metastatic Nectin-4 positive TNBC.

About 9MW2821

9MW2821 is the first site-specific conjugated novel Nectin-4-targeting ADC developed by Mabwell using ADC platform and automated high-throughput hybridoma antibody molecular discovery platform, and is the first drug candidate to enter clinical study among the Nectin-4-targeting ADCs developed by Chinese companies, and the first therapeutic drug candidate targeting Nectin-4 in the world to reveal clinical efficacy data of cervical cancer (CC), esophageal cancer (EC) and breast cancer. 9MW2821 has been granted FTD by FDA for the treatment of advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) in Feb. 2024, and also respectively granted Orphan Drug Designation (ODD) and FTD for the treatment of EC and recurrent or metastatic CC progressed on or following prior treatment with a platinum-based chemotherapy regimen in May 2024. Then, it has been granted FTD for the treatment of locally advanced or metastatic Nectin-4 positive TNBC in July, 2024.

9MW2821 achieves site-specific modification of antibody through proprietary conjugate technology linkers and optimized ADC conjugation process. After injection, 9MW2821 can specifically bind to Nectin-4 on the cell membrane surface, be internalized and release cytotoxic drug, and induce the apoptosis of tumor cells.

On July 15, 2024, Pulse Biosciences, Inc. (the "Company") reported to have entered into an equity distribution agreement (the "Distribution Agreement") with Canaccord Genuity LLC and Needham & Company, LLC (each a "Sales Agent" and together, the "Sales Agents"), as sales agents, pursuant to which the Company may offer and sell, from time to time, through the Sales Agents, shares of the Company’s common stock, par value $0.001 per share (the "Common Stock"), having an aggregate offering price of up to $60.0 million (the "Shares") (Filing, 8-K, Pulse Biosciences, JUL 15, 2024, View Source [SID1234644873]).

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The Company is not obligated to sell any Shares under the Distribution Agreement. Subject to the terms and conditions of the Distribution Agreement, the Sales Agents will use commercially reasonable efforts, consistent with their normal trading and sales practices, to sell Shares from time to time based upon the Company’s instructions, including any price, time or size limits or other customary parameters or conditions specified by the Company. Under the Distribution Agreement, the Sales Agents may sell Shares in transactions that are deemed to be "at the market" offerings as defined in Rule 415(a)(4) under the Securities Act of 1933, as amended (the "Securities Act"), including sales made by means of ordinary brokers’ transactions, including directly on the Nasdaq Capital Market or into any other existing trading market for the Shares, or sales made to or through a market maker, in block transactions or by any other method permitted by law, including negotiated transactions. Sales may be made at market prices prevailing at the time of a sale or at prices related to prevailing market prices or at negotiated prices. The Company will pay the Sales Agents a commission of up to 3.0% of the gross sales price per share sold by the Sales Agents. The Company also will reimburse the Sales Agents for certain specified expenses in connection with entering into the Distribution Agreement. The Company has no obligation to sell any of the Shares under the Distribution Agreement and may at any time suspend solicitations and offers under the Distribution Agreement.

The issuance and sale, if any, of the Shares by the Company under the Distribution Agreement will be made pursuant to the Company’s effective registration statement on Form S-3 (File No. 333-278322) filed with the U.S. Securities and Exchange Commission (the "SEC") on March 28, 2024, and declared effective as of April 8, 2024, as well as a related registration statement on Form S-3 (File No. 333-280805), filed with the SEC on July 15, 2024 pursuant to Rule 462(b) of the Securities Act, which became effective immediately upon filing. The Company filed a prospectus supplement with the SEC on July 15, 2024 in connection with the offer and sale of the Shares pursuant to the Distribution Agreement.

The foregoing description of the Distribution Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Distribution Agreement, a copy of which is filed as Exhibit 1.1 to this Current Report on Form 8-K and is incorporated herein by reference. The legal opinion of Baker & Hostetler LLP, counsel to the Company, relating to the validity of the issuance and sale of the Shares being offered pursuant to the Distribution Agreement, is filed as Exhibit 5.1 to this Current Report on Form 8-K and is incorporated herein by reference.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy any Shares under the Distribution Agreement nor shall there be any sale of such Shares 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.

On July 15, 2024 Peptomyc S.L., a company developing foundational mini-protein therapeutics for the treatment of cancer, reported that the Company has been issued a patent by both the Indian and the European Patent Office protecting its Methods and Composition of Matter (Press release, Peptomyc, JUL 15, 2024, View Source [SID1234644872]).

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"We are delighted to announce further protection of our mini-protein therapeutics in Europe and India. This patent grants add to similar ones in the major geographical areas in oncology, strengthening our patent portfolio and protecting our unique mini-protein therapeutics, which are able to inhibit MYC, the most dysregulated oncogene in human cancer" said Laura Soucek, CEO at Peptomyc S.L.

The Company currently maintains over 10 different patent families worldwide covering applications protecting Peptomyc S.L. first-in-modality mini-protein therapeutics in multiple oncological indications, and counts on the services of ABG Intellectual Property and Dechert LLP for the protection of its IP assets.

On July 15, 2024 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported that enrollment has been completed and dosing initiated for the sixth dose cohort of its Phase 1/2 study of ONCT-534 for the treatment of patients with metastatic castration-resistant prostate cancer who are relapsed or refractory to approved androgen receptor pathway inhibitors (ARPI) (Press release, Oncternal Therapeutics, JUL 15, 2024, https://investor.oncternal.com/news-releases/news-release-details/oncternal-announces-enrollment-completed-and-dosing-initiated-0 [SID1234644871]). Patients in the sixth cohort are receiving ONCT-534, the company’s dual-action androgen receptor inhibitor (DAARI), at a dose of 1200 mg taken orally once each day. The decision to proceed to this higher dose level was made by the study’s Safety Review Committee (SRC) after reviewing data from the fifth dose level of 600 mg ONCT-534 daily. An initial update on ONCT-534 safety and efficacy based on prostate–specific antigen (PSA) levels from this study is expected in the third quarter of 2024 and will include data from this 1200 mg dose cohort.

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"We are encouraged by the rapid enrollment in the dose escalation portion of our Phase 1/2 study with ONCT-534. The drug has been well tolerated, with no dose limiting toxicities observed to date. Patient demand continues to be strong," said Salim Yazji M.D., Chief Medical Officer at Oncternal Therapeutics. "We are looking forward to sharing initial safety and efficacy data soon, which will include a larger, more robust set of clinical and biomarker results, as well as longer follow-up from the earlier dosing cohorts."

About Study ONCT-534-101
Study ONCT-534-101 is a Phase 1/2, single-arm, open-label, multi-center study to evaluate the safety and tolerability, pharmacokinetics, and preliminary anti-tumor activity of ONCT-534 in patients with mCRPC who have relapsed or are refractory to approved ARPIs including enzalutamide, abiraterone, apalutamide, and darolutamide. After the safety and tolerability and preliminary antitumor activity of ONCT-534 have been assessed in Phase 1, Phase 2 will commence to further evaluate the safety and antitumor activity of ONCT-534 to support selecting an optimal dose.