On November 20, 2024 Pasithea Therapeutics Corp. (NASDAQ: KTTA) ("Pasithea" or the "Company"), a clinical-stage biotechnology company developing PAS-004, a next-generation macrocyclic MEK inhibitor, for the treatment of neurofibromatosis type 1 (NF1) and other cancer indications, reported that the external Safety Review Committee recommended proceeding to cohort 4, 15mg capsule, without modifications (Press release, Pasithea Therapeutics, NOV 20, 2024, View Source [SID1234648521]). This recommendation was based on the absence of any dose limiting toxicities (DLT’s). In addition, no rash was observed in any of the first 9 patients who received PAS-004. The Company has decided to add a cohort 4b to the trial, which will consist of 3 additional patients and introduce an alternate formulation which is intended for commercial use.

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Dr. Tiago Reis Marques, Chief Executive Officer of Pasithea stated, "We are pleased to observe that as we continue to dose escalate, we have not yet seen rash emerge. Rash is a common adverse event (AE) that is observed at low doses with competitor MEK inhibitors and may lead to the high discontinuation rate in real world practice. In addition, we are excited to dose patients with our potential commercial formulation."

The Phase 1 clinical trial is a multi-center, open-label, dose escalation 3+3 study design to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy of PAS-004 in patients with MAPK pathway driven advanced solid tumors with a documented RAS, NF1 or RAF mutation, or patients who have failed BRAF/MEK inhibition (NCT06299839).

PAS-004 Demonstrates a Differentiated MEK Inhibitor Profile

Unlike first-generation MEK inhibitors for the treatment of NF1 that require twice-daily dosing (BID) and exhibit short half-lives (<8 hours), PAS-004 has the potential to achieve prolonged target inhibition and once-daily dosing (QD) due to its long half-life of approximately 70 hours. As disclosed previously, the PK profile shows consistent plasma levels at steady-state, as reflected by a low Cmax to Cmin ratio, potentially reducing the risks for Cmax-related toxicity. These findings provide a compelling rationale for the advancement of PAS-004 into clinical trials for both the treatment of cutaneous and plexiform neurofibromas in NF1, cancer and other MAPK-driven opportunities. The company expects to provide additional trial updates on a periodic basis as the trial progresses.

On November 20, 2024 Novavax presented its corporate presentation (Press release, Novavax, NOV 20, 2024, View Source [SID1234648520]).

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On November 20, 2024 Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company developing novel, investigational engineered therapies targeting cytokine pathways designed to address areas of unmet need for patients with a variety of cancers, reported the publication of previously reported clinical data demonstrating tolerability and antitumor activity from ARTISTRY-1, a phase 1/2 trial of the company’s lead candidate, nemvaleukin alfa (nemvaleukin) (Press release, Mural Oncology, NOV 20, 2024, View Source [SID1234648519]). The paper, titled "Nemvaleukin alfa as monotherapy and in combination with pembrolizumab in advanced solid tumors: the phase 1/2, non-randomized ARTISTRY-1 trial," was published in the Journal for ImmunoTherapy of Cancer (JITC).

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"While immunotherapies have marked a paradigm shift in the treatment of some types of cancers, many patients still face challenges, including lack of response, tolerability issues, or resistance to therapy, and there remains a great deal of unmet clinical need. In the ARTISTRY-1 study, notable antitumor activity of nemvaleukin was observed in both monotherapy and combination therapy. What was most striking were the durable and complete responses in platinum-resistant ovarian cancer, which does not usually respond to immunotherapy. These clinical data provide a solid foundation for Mural’s ongoing late-stage trials," said Ulka Vaishampayan, MD, Professor, Internal Medicine, Division of Hematology/Oncology at the University of Michigan and the paper’s lead author.

Nemvaleukin is a novel, engineered fusion protein designed to leverage the antitumor effects of the IL-2 pathway while mitigating aldesleukin’s toxicity. ARTISTRY-1 was a three-part, open-label, phase 1/2 study evaluating the safety, tolerability, and efficacy of both nemvaleukin monotherapy and combination therapy with pembrolizumab. The study was conducted at 32 sites in seven countries, with 286 patients with advanced solid tumors enrolled and treated from July 2016 to March 2023.

ARTISTRY-1 is the foundation of Mural’s two ongoing potentially registrational trials, with data readouts expected in late Q1/early Q2 2025 for platinum-resistant ovarian cancer (PROC) and Q2 2025 for mucosal melanoma.

Key Findings:

As previously reported, nemvaleukin was generally well tolerated and demonstrated promising antitumor activity alone and in combination with pembrolizumab across heavily pretreated patients with advanced solid tumors. Robust expansion of CD8+ T cells and natural killer (NK) cells, with minimal expansion of regulatory T (Treg) cells were observed following treatment, thus supporting the design hypothesis of nemvaleukin.

Monotherapy:

10% overall response rate (ORR) with nemvaleukin monotherapy (7/68; 95% CI 4 to 20), with all seven confirmed partial responses (melanoma, n=4; renal cell carcinoma, n=3).
33.3% ORR in patients with mucosal melanoma, with two partial responses (one confirmed, one unconfirmed) in six evaluable patients. All responders had been on prior CPI therapy and progressed.
Combination therapy:

13% ORR with nemvaleukin and pembrolizumab (19/144; 95% CI 8 to 20), with five confirmed complete responses and 14 confirmed partial responses. Six responses were in PD-(L)1 inhibitor-approved and five in PD-(L)1 inhibitor-unapproved tumor types.
21% ORR in patients with PROC: Notably, there were three confirmed responses (two complete, one partial) in 14 evaluable patients with PROC, which does not normally respond to immunotherapy and for which there are no approved immunotherapies. Additionally, there was one unconfirmed partial response.
Durable, stable disease for greater than 6 months was observed in patients with cervical cancer, bladder cancer, non-small-cell lung cancer, PROC, and endometrial cancer.
Safety and Tolerability:

Nemvaleukin was administered in an outpatient setting throughout treatment and had a manageable safety profile, with a low rate (4%) of discontinuation due to adverse events.
Most common grade 3-4 treatment-related adverse events (TREAs) were neutropenia and anemia.

On November 20, 2024 Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, reported that it entered into definitive agreements with certain healthcare focused institutional investors and with Broadwood Partners, L.P. ("Broadwood"), an affiliate of Neal Bradsher, a member of Lineage’s board of directors, for the purchase and sale of up to an aggregate of 39,473,688 of Lineage’s common shares and accompanying warrants (the "common warrants") to purchase an aggregate of up to 39,473,688 of Lineage’s common shares at a combined purchase price of $0.76 per common share and accompanying common warrant, in a registered direct offering (Press release, Lineage Cell Therapeutics, NOV 20, 2024, View Source [SID1234648518]). Each common warrant will be exercisable for one common share at an exercise price of $0.91 per common share and will be exercisable commencing six months following their date of issuance and will expire on the earlier of (a) the three-year anniversary of the initial exercise date, and (b) the 90th day following the date of the public disclosure of the intent to advance OpRegen (also known as RG6501) into a multi-center phase 2 or 3 clinical trial which includes a control or comparator arm, or if the date of such public disclosure occurs prior to the initial exercise date of the common warrants, the 90th day following the initial exercise date. However, the common warrants that may be issued to Broadwood will not be exercisable until the later of (i) their date of issuance, which will be the date shareholder approval is obtained, and (ii) the six-month anniversary of the date of issuance of the common warrants to the unaffiliated institutional investors in the offering.

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H.C. Wainwright & Co. is serving as the exclusive placement agent for the offering.

The offering of the securities to the unaffiliated institutional investors is expected to close on or about November 21, 2024, subject to the satisfaction of customary closing conditions. The offering of the securities to Broadwood is expected to close upon obtaining shareholder approval to satisfy applicable NYSE American rules and to the satisfaction of customary closing conditions.

Lineage expects to receive $24 million in aggregate gross proceeds from the offering with respect to the investments by the unaffiliated institutional investors, and approximately $6 million in aggregate gross proceeds from the offering with respect to the investment by Broadwood, in each case, before deducting the placement agent’s fees and other offering expenses payable by Lineage. The potential additional gross proceeds to Lineage from the common warrants, if fully exercised on a cash basis, will be approximately $36 million. No assurance can be given that Lineage will obtain the shareholder approval required to satisfy applicable NYSE American rules in order to sell the securities in the offering to Broadwood or that any of the common warrants will be exercised. Lineage currently plans to use the net proceeds from the offering for working capital and general corporate purposes, including research and development expenses and capital expenditures.

The securities described above are being offered and sold by Lineage in a registered direct offering pursuant to a "shelf" registration statement on Form S-3 (File No. 333-277758) filed with the Securities and Exchange Commission (the "SEC") on March 7, 2024, and which was declared effective by the SEC on May 14, 2024. The offering of the securities in the registered direct offering is being made only by means of a base prospectus and a prospectus supplement that forms a part of the effective registration statement. A final prospectus supplement and the accompanying base prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Electronic copies of the final prospectus supplement and the accompanying base prospectus may also be obtained, when available, from H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by phone at (212) 856-5711 or e-mail at [email protected].

On November 20, 2024 Kura Oncology, Inc. (Nasdaq: KURA) and Kyowa Kirin Co., Ltd. (TSE: 4151) reported they have entered into a global strategic collaboration to develop and commercialize ziftomenib, Kura’s selective oral menin inhibitor, being investigated for the treatment of patients with acute myeloid leukemia (AML) and other hematologic malignancies (Press release, Kura Oncology, NOV 20, 2024, View Source [SID1234648517]).

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Under the terms of the agreement, Kura will receive an upfront payment of $330 million and expects to receive up to $420 million in near-term milestone payments, including a payment upon the launch of ziftomenib in the monotherapy relapsed/refractory (R/R) setting. In addition, Kura is eligible to receive additional development, regulatory and commercial milestone payments of $741 million, totaling up to $1.161 billion in payments for milestones and the opt-in for solid tumor indications.

In the U.S., Kura will lead development, regulatory and commercial strategy and be responsible for manufacturing ziftomenib. The companies will jointly perform commercialization activities in accordance with a co-created U.S. territory commercialization plan and will share equally in any potential profits and losses.

Outside the U.S., Kyowa Kirin will lead development, regulatory and commercial strategy and is responsible for commercializing ziftomenib. Kura will be eligible to receive tiered double-digit royalties on net product sales.

As a Japan based global specialty pharmaceutical company, Kyowa Kirin aims to create treatments with life-changing value that bring smiles to people living with disease. The company will leverage its hemato-oncology experience and capabilities, and its deep commitment to partnerships, to successfully bring ziftomenib to market globally.

"We believe that ziftomenib is a very promising investigational treatment for genetically defined AML patients," said Yasuo Fujii, MBA, Chief Strategy Officer, Managing Executive Officer of Kyowa Kirin. "The addition of ziftomenib will complement Kyowa Kirin’s existing hemato-oncology portfolio and pipeline and expand our clinical development efforts into combination therapies designed to generate improved outcomes for cancer patients. We look forward to collaborating closely with the team at Kura and adding ziftomenib to our portfolio of oncology candidates as part of our commitment to bringing new, advanced treatment options to patients and the clinical community around the world."

Ziftomenib is the first and only investigational therapy to receive breakthrough designation from the U.S. Food and Drug Administration (FDA) for the treatment of R/R NPM1-mutant AML, a mutation that is associated with poor outcomesi,ii,iii. Enrollment in a Phase 2 registration-directed trial of ziftomenib in R/R NPM1-mutant AML has been completed and the companies anticipate submission of a New Drug Application (NDA) in 2025. Kura is also conducting a series of clinical trials to evaluate ziftomenib in combination with current standards of care in newly diagnosed and R/R NPM1-mutant and KMT2A-rearranged AML. Kura expects to initiate registrational Phase 3 frontline studies in both the fit and unfit frontline AML patient populations in 2025.

"This collaboration is an important step toward fulfilling Kura’s commitment to realizing the promise of precision medicines for the treatment of cancer, and it substantially advances our goal of building a sustainable, fully integrated biopharmaceutical company," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "Kyowa Kirin is a wonderful partner for Kura, bringing the expertise and scale of a global pharmaceutical company. On behalf of our leadership team and board of directors, we are thrilled to be working with Kyowa Kirin to realize the potential of ziftomenib as a transformational therapy for AML patients."

"Importantly," Dr. Wilson continued, "we believe the upfront and anticipated milestone payments from this collaboration combined with our current cash position should provide sufficient funding to support the ziftomenib program to commercialization in the frontline setting, which we believe is a market opportunity of up to $3 billion annually in the U.S. alone."

Additional Details About the Collaboration

Following regulatory approval, Kura will book sales and take the lead role in U.S. commercial strategy development and both parties will share in commercialization activities. Profits and losses from the commercialization activities will be shared equally in the U.S. Outside the U.S., Kyowa Kirin will lead and perform commercialization activities, book sales and be responsible for the conduct and funding of commercialization of ziftomenib, and Kura is eligible to receive tiered double-digit royalties on net product sales.

As part of the strategic collaboration, the companies will share responsibility for the conduct of clinical trials delineated within an agreed-upon global development plan. For the global development plan, Kura will fund the development costs until the end of 2028, and from 2029 onwards, both companies will share the costs at a 50:50 ratio. The companies will share equally the funding of future trials in the U.S. The agreement includes plans to launch multiple Phase 2 and Phase 3 studies of ziftomenib in AML and other hematologic malignancies over the next several years. Development and commercialization activities under the collaboration will be managed through a shared governance structure.

Under the Agreement, Kyowa Kirin has an option to participate in the development and commercialization of ziftomenib in gastrointestinal stromal tumors (GIST) and other solid tumor indications upon opt-in after receipt of clinical data from the ongoing proof-of-concept study evaluating ziftomenib and imatinib in patients with advanced GIST not successfully treated with imatinib. If Kyowa Kirin exercises its option, Kura is eligible for upfront and milestone payments totaling $228 million and the parties’ roles and responsibilities follow the same structure as the collaboration in AML and other heme malignancies. Excluded from the collaboration are Kura’s ongoing efforts to advance multiple, next-generation menin inhibitor drug candidates targeting certain oncology indications, as well as diabetes and other metabolic diseases.

Kura was advised in the transaction by BofA Securities and represented by Cooley LLP.

Conference Call

Kura will host a webcast and conference call featuring management from both companies at 5:30 pm ET today, November 20, 2024. The live call may be accessed by dialing (800) 715-9871 for domestic callers and (646) 307-1963 for international callers and entering the conference ID: 6978447. A live webcast will be available here and in the Investors section of Kura’s website, with an archived replay available shortly after the event.

About Ziftomenib

Ziftomenib is a selective and oral menin inhibitor currently in development for the treatment of genetically defined AML patients with high unmet need. In April 2024, ziftomenib received Breakthrough Therapy Designation (BTD) by the FDA for the treatment of R/R NPM1-mutant AML based on data from Kura’s ongoing KOMET-001 clinical trial. Additional information about clinical trials for ziftomenib can be found at kuraoncology.com/clinical-trials/#ziftomenib.