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.

On November 20, 2024 Valora Therapeutics Inc. ("Valora"), a biotechnology company pioneering a novel approach to immunotherapy, reported the successful closing of its seed funding round (Press release, Valora Therapeutics, NOV 20, 2024, View Source [SID1234648535]). The investment was co-led by Avalon BioVentures, a top-tier investor group with a long history of nurturing groundbreaking life science companies from inception to exit, together with Bregua Corporation and TigerGene, investors recognized for their expertise in supporting innovative biotech companies. Additional participation was provided by Alexandria Venture Investments and Correlation Ventures. This significant investment will propel the advancement of Valora’s proprietary AbLec platform to develop novel immunotherapeutics.

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"The AbLec platform represents a significant leap forward in manipulating glycoimmunology and unlocking new paradigms in immunotherapy. I look forward to providing scientific support to Valora as it advances lead molecules toward clinical development."

Valora’s AbLec (Antibody-Lectin chimera) platform is expected to offer a fresh perspective on restoring proper immunological competency. By precisely targeting specific sugar molecules on cells, AbLecs modulate glyco-immune checkpoints—a key control point in the body’s immune response. This innovative approach holds significant potential for developing first-in-class and best-in-class therapeutics in oncology, autoimmune diseases, and other therapeutic areas. The technology is exclusively licensed from Stanford University. It builds upon the transformative work performed at the Stanford laboratory of Dr. Carolyn Bertozzi, recipient of the 2022 Nobel Prize in Chemistry, and a world leader in glycobiology, together with Dr. Jessica Stark, who is currently an Assistant Professor of Biological Engineering and Chemical Engineering at the Massachusetts Institute of Technology. Both Drs. Carolyn Bertozzi and Jessica Stark are scientific founders and advisors for Valora.

"We are incredibly honored to partner with highly recognized investors and Valora’s scientific founders, Dr. Carolyn Bertozzi and Dr. Jessica Stark, to develop the AbLec platform as a trailblazing approach for next-generation immunomodulators," said Miguel Garcia-Guzman, Ph.D., Valora’s CEO. "This funding allows us to accelerate our R&D efforts, optimizing the AbLec platform and advancing AbLec therapeutics toward the clinic. We take great pride in the work we do at Valora and are deeply grateful for the support of our investors."

Dr. Stark added, "The AbLec platform represents a significant leap forward in manipulating glycoimmunology and unlocking new paradigms in immunotherapy. I look forward to providing scientific support to Valora as it advances lead molecules toward clinical development."

The seed funding will enable Valora to further explore and develop the full potential of the AbLec platform, validating specific mechanisms of action, and advancing lead molecules into preclinical development. Valora has established its R&D operations at the Avalon BioVentures Accelerator in San Diego, California, providing access to a supportive ecosystem of biotech experts and resources.

Sandy Madigan, Ph.D., Managing Partner at Avalon BioVentures and a Board Member of Valora Therapeutics, stated, "We are excited to co-lead the seed funding round for Valora. We believe Valora has the team and resources to lead the development of novel AbLec therapeutics and to rapidly advance this groundbreaking technology toward the clinic."

Stefan Heller, Ph.D., who represents Bregua Corporation on the Board of Valora Therapeutics, added, "We are excited to collaborate with Valora’s team to advance the AbLec platform for developing novel therapies. This innovative approach has promising potential for creating leading-edge treatments across a range of therapeutic areas."

Audrey Warner, Partner at TigerGene and Director of Valora Therapeutics concluded, "We are very excited to partner with Valora’s team to explore the promise of glyco-immune checkpoint modulation and deliver innovative biological therapeutics to alleviate patient suffering across a multitude of indications."

On November 20, 2024 The Cancer Prevention & Research Institute of Texas (CPRIT) reported that it plans to award Orphagen a $10.2 M product development grant over three years to partially fund the final steps towards IND filing and a Phase 1 clinical trial of OR-449, a novel small molecule and orally-bioavailable therapeutic candidate for an intractable cancer, adrenocortical cancer (ACC) (Press release, Orphagen, NOV 20, 2024, View Source [SID1234649065]). OR-449 may be developed subsequently in head & neck and lung squamous cancers as a precision therapy for the 3-10% of these tumors where its target is highly expressed. Details of today’s announcement are here: CPRIT.grants.announcement.Nov.20.2024.

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A major site for the Phase 1 trial would be the MD Anderson Cancer Center in Houston, internationally recognized for its expertise in treatment of ACC. To initiate and fully comply with the CPRIT grant, Orphagen will raise additional matching funds and move its headquarters to Texas in 2025.

Scott Thacher, Orphagen’s CEO and founder, stated, "This is an important step forward for our programs. OR-449 is the first of our internal programs that is on the path to a Phase 1 trial."

"Further OR-449 represents a significant opportunity for improved therapy of ACC patients, whose options for medical therapy are limited. The target of OR-449 is the orphan nuclear receptor SF-1, now recognized as a potential driver of ACC."

Orphagen Pharmaceuticals is a preclinical stage biopharmaceutical company focused on discovering and developing first-in-class therapeutics for cancer and inflammatory disease. Orphagen is a pioneer in the screening, discovery and development of ligands that modulate orphan or unexplored members of the nuclear receptor family. On a per target basis, the nuclear receptors are one of the most successful target classes known to the pharmaceutical industry.

Its first-in-class SF-1 antagonist (OR-449) has practically completed IND-enabling studies. Potential expansion indications for OR-449 include other cancers where SF-1 expression is highly elevated in such a way to suggest these depend on SF-1 activity for tumor growth.

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 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.