On May 14, 2024 Nykode Therapeutics ASA (OSE: NYKD), a clinical-stage biopharmaceutical company dedicated to the discovery and development of novel immunotherapies, reported that it has expanded its collaboration with MSD (Merck & Co., Inc., Rahway, NJ, USA) to include a clinical trial collaboration and supply agreement for a phase 2 trial evaluating Nykode’s wholly-owned lead candidate, VB10.16, in combination with MSD’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) (Press release, Nykode Therapeutics, MAY 14, 2024, View Source [SID1234643233]). This study will enroll HPV16-positive high-risk patients with locally advanced cervical cancer undergoing chemoradiotherapy.

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VB10.16 is a potentially first-in-class off-the-shelf therapeutic cancer vaccine specifically designed to treat HPV16-induced malignancies. The cancer vaccine is built on Nykode’s technology platform of targeting antigens to antigen presenting cells. Nykode has reported promising data from the phase 2 VB C-02 trial (NCT04405349) in heavily pre-treated cervical cancer patients receiving VB10.16 in combination with atezolizumab with a median overall survival not yet reached (estimated to 25 months at the time of analysis). These data support Nykode’s ongoing efforts with the phase 2 VB-C-04 trial (NCT06099418) in second-line recurrent/metastatic cervical cancer. Furthermore, the VB10.16 clinical development program is expanding into new indications, including head and neck cancer, for which Nykode has an existing clinical trial collaboration and supply agreement with MSD for the ongoing VBC-03 trial (NCT06016920) evaluating VB10.16 in combination with KEYTRUDA in patients with HPV16-positive, PD-L1-positive, recurrent or metastatic head and neck squamous cell carcinoma.

Agnete Fredriksen, EVP, Chief Scientific Officer and Business Development, commented, "We are excited to expand our clinical development to include earlier stages of cervical cancer where there is a significant unmet medical need, and we see a huge potential for cancer vaccines. We are thrilled to continue building on our already established, highly valued collaboration with the experienced and talented team at MSD, a global leader in immuno-oncology."

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

On May 14, 2024 NANOBIOTIX (Euronext: NANO –– NASDAQ: NBTX – the ‘‘Company’’), a late-clinical stage biotechnology company pioneering nanoparticle-based therapeutic approaches to expand treatment possibilities for patients with cancer and other major diseases, reported that the U.S. Food and Drug Administration ("US FDA") issued a Study May Proceed Letter for a randomized Phase 2 study evaluating NBTXR3 for the treatment of patients with stage 3, unresectable non-small cell lung cancer ("NSCLC") (Press release, Nanobiotix, MAY 14, 2024, View Source [SID1234643232]). An IND to support this trial was submitted by the global trial sponsor, Johnson & Johnson Enterprise Innovation Inc., a Johnson & Johnson company.

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"The NBTXR3 collaboration established by our global licensing agreement with Janssen Pharmaceutica NV continues to make progress toward our goal of reaching millions of patients with cancer around the world. The US FDA acceptance of the protocol for this new Phase 2 study has the potential to expand the NBTXR3 development pipeline to a new indication where innovation could potentially provide important outcomes," said Louis Kayitalire, MD, chief medical officer at Nanobiotix. "We look forward to continuing to prepare for the launch of the study."

About NBTXR3
NBTXR3 is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. Its proof-of-concept was achieved in soft tissue sarcomas for which the product received a European CE mark in 2019. The product candidate’s physical mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the physical MoA, Nanobiotix believes that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.

Radiotherapy-activated NBTXR3 is being evaluated across multiple solid tumor indications as a single agent or in combination with anti-PD-1 immune checkpoint inhibitors, including in NANORAY-312—a global, randomized Phase 3 study in locally advanced head and neck squamous cell cancers. In February 2020, the United States Food and Drug Administration granted regulatory Fast Track designation for the investigation of NBTXR3 activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy—the same population being evaluated in the Phase 3 study.

Given the Company’s focus areas, and balanced against the scalable potential of NBTXR3, Nanobiotix has engaged in a collaboration strategy to expand development of the product candidate in parallel with its priority development pathways. Pursuant to this strategy, in 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several Phase 1 and Phase 2 studies evaluating NBTXR3 across tumor types and therapeutic combinations. In 2023, Nanobiotix announced a license agreement for the global co-development and commercialization of NBTXR3 with Janssen Pharmaceutica NV.

On May 14, 2024 Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company developing novel, investigational engineered cytokine therapies designed to address areas of unmet need for patients with a variety of cancers, reported financial results for the first quarter of 2024 and provided a business update (Press release, Mural Oncology, MAY 14, 2024, View Source [SID1234643231]).

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"We remain on track to share data readouts in the first half of next year from our two late-stage, potentially registrational studies of nemvaleukin. We are also excited about the potential of our less frequent dosing regimen of nemvaleukin that we are evaluating in a clinical trial as announced in March," said Caroline Loew, Ph.D., CEO of Mural Oncology. "As we look to further strengthen our pipeline, we have made progress with our preclinical programs for interleukin-18 (IL-18) and IL-12. Both are targets that have generated a great deal of interest in the immuno-oncology space, and we are diligently working to make candidate nominations for each program. We continue to be well capitalized to achieve our key clinical readouts and are laser-focused on the delivery of our goals."

Recent Corporate Highlights and Upcoming Milestones

The company’s late-stage clinical trials remain on track, with details as follows:
ARTISTRY-7 is a potentially registrational, phase 3 clinical trial evaluating nemvaleukin in combination with pembrolizumab compared to investigators’ choice of chemotherapy in approximately 448 patients with platinum-resistant ovarian cancer. Mural expects to report interim overall survival (OS) results based on approximately 75% of events in the first quarter of 2025. The company anticipates reporting final OS results in the second quarter of 2026.
Cohort 2 of ARTISTRY-6 is a potentially registrational, phase 2 clinical trial evaluating nemvaleukin as a monotherapy in 90 patients with mucosal melanoma. The company expects to report top-line data results from cohort 2 of ARTISTRY-6 in the first half of 2025.
Mural is evaluating a newly selected dose of less-frequent intravenous (LFIV) nemvaleukin in open-label cohorts of patients with cutaneous melanoma in ARTISTRY-6. The new dosing regimen is a shift from five daily infusions (days 1-5) to two infusions (days 1 and 8), per three-week cycle. The company expects preliminary data readouts in the monotherapy cohort in the first half of 2025, and in the combination cohort with pembrolizumab in the second half of 2025.
The company looks forward to presenting data from ARTISTRY-3, an evaluation of the LFIV dosing of nemvaleukin, at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in June 2024.
Mural presented IL-18 and IL-12 preclinical data for the first time at the American Association of Clinical Research (AACR) (Free AACR Whitepaper) annual meeting in April 2024 that outlined the company’s novel approach to protein engineering. Both poster presentations are available at www.muraloncology.com/publications.
IL-18 poster synopsis: Native IL-18 is a potent immune-stimulating cytokine, but its efficacy is blunted by IL-18 binding protein (IL-18BP), a high affinity decoy receptor that binds to, and neutralizes, IL-18, thereby rendering it ineffective. Its potency is also limited by its short half-life. Mural’s IL-18 variant contains mutations designed to eliminate binding to IL-18BP while minimally impacting the native IL-18 structure. The company has also fused IL-18 to protein scaffolds to extend the half-life and increase IL-18’s exposure. Together, these may lead to a more durable immunological effect.
IL-12 poster synopsis: Native IL-12 is a highly potent pro-inflammatory cytokine, but because of its very narrow therapeutic index, it can be toxic with systemic exposure. Mural’s IL-12 variant splits the molecule into two inactive monomers: IL12p35 and IL-12p40. These individual subunits are then separately fused to antibody fragments, which deliver and concentrate IL-12 specifically in the tumor microenvironment with the goal of limiting systemic exposure.
Mural intends to nominate development candidates for these investigational engineered IL-18 and IL-12 cytokine therapies later this year.
Financial Results for the Quarter Ended March 31, 2024

Cash Position: As of March 31, 2024, cash, cash equivalents, and marketable securities were $231.7 million.
R&D Expenses: Research and development expenses were $26.9 million for the first quarter of 2024 compared to $40.4 million for the first quarter of 2023. The decrease in expenses was primarily related to decreased headcount compared to the headcount allocated to the company by the former parent prior to the separation, decreased spend on the ARTISTRY-1 and ARTISTRY-2 trials as activities related to the ARTISTRY-1 and ARTISTRY-2 trials wound down in 2023, and decreased manufacturing spend on other programs. These decreases were partially offset by increased spend on the ARTISTRY-7 trial related to increased enrollment and associated clinical trial expenses.
G&A Expenses: General and administrative expenses were $7.2 million for the first quarter of 2024 compared to $3.7 million for the first quarter of 2023. The increase in expenses was primarily due to increases in employee-related expenses and professional fees associated with operating as a standalone public company after the separation.
Net Loss: Net loss was $30.9 million for the first quarter of 2024 compared to $46.5 million for the first quarter of 2023.
Financial Guidance

The company reaffirms guidance that its cash, cash equivalents, and marketable securities are expected to fund its operations into the fourth quarter of 2025.
As noted in the 2023 year-end financial results press release, Mural anticipates reporting lower year-over-year operating expenses in 2024. Also, management forecasts higher operating expenses in 2024 versus 2025 due to the timing of clinical trial expenses.
About Nemvaleukin
Nemvaleukin alfa (nemvaleukin) is a novel, engineered cytokine designed to leverage antitumor effects of the IL-2 pathway while mitigating its hallmark toxicities that limit its use. Nemvaleukin selectively binds to the intermediate-affinity IL-2 receptor (IL-2R) and is sterically occluded from binding to the high-affinity IL-2R. Because of this molecular design, nemvaleukin treatment leads to preferential expansion of antitumor CD8+ T cells and natural killer cells, with minimal expansion of immunosuppressive regulatory T cells. Nemvaleukin is currently being evaluated in two potentially registrational late-stage trials.

About Mural Oncology’s IL-18 Program
IL-18 is a potent immune-stimulating cytokine, but its efficacy is blunted by IL-18 binding protein (IL-18BP), a high affinity decoy receptor that binds to, and neutralizes, IL-18, thereby rendering it ineffective. Native IL-18’s potency is also limited by its short half-life. Mural Oncology’s novel approach to protein engineering is designed to mitigate these issues. First, Mural introduced mutations to IL-18 that eliminate binding to IL-18BP while minimally impacting the native IL-18 structure. Second, it fused IL-18 to protein scaffolds which extend the half-life and increase IL-18’s exposure. Together, these have demonstrated more durable immunological effect in preclinical studies. Mural intends to nominate a development candidate for its IL-18 program by the end of this year.

About Mural Oncology’s IL-12 Program
Native IL-12 is a highly potent pro-inflammatory cytokine, but because of its very narrow therapeutic index, it can also be toxic with systemic exposure. To mitigate this hallmark toxicity, Mural, through its novel approach to protein engineering, split the IL-12p70 heterodimer into two inactive monomers: IL12p35 and IL-12p40. These individual subunits are then separately fused to antibody fragments and sequentially injected, which deliver and concentrate IL-12 specifically in the tumor microenvironment to limit systemic exposure. In preclinical studies, Mural’s engineered IL-12 achieved the desired reduction in serum while maintaining tumor concentrations providing the potential to reduce systemic toxicities. Mural intends to nominate a development candidate for its IL-12 program by the end of this year.

On May 14, 2024 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported that it has completed enrollment of 85 patients in the Phase 2 portion of KOMET-001, a registration-directed clinical trial of the Company’s menin inhibitor, ziftomenib (KO-539), in patients with relapsed or refractory (R/R) NPM1-mutant acute myeloid leukemia (AML) (Press release, Kura Oncology, MAY 14, 2024, View Source [SID1234643230]). The Company expects to report topline data from the trial in early 2025.

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"We are thrilled to announce this critical milestone, which brings us one step closer to delivering ziftomenib as a potentially best-in-class treatment for patients with genetically defined acute leukemias," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "Our confidence is supported by our recently announced Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA), which recognizes ziftomenib’s potential as an innovative medicine for patients with R/R NPM1-mutant AML and is intended to expedite review as we prepare for submission of a New Drug Application. We are grateful for the KOMET-001 investigators, patients and their families, and we look forward to sharing topline data from this pivotal study early next year."

Kura announced the first patients dosed in the Phase 2 portion of KOMET-001 in February 2023. The registration-directed study is designed to assess evidence of clinical activity, safety and tolerability of ziftomenib in patients with R/R NPM1-mutant AML, with a primary endpoint of complete response. The study has completed enrollment of the 85 patients necessary to support the primary endpoint analysis.

"The rapid enrollment of this study reflects the urgent need for more effective treatment options in AML as well as the potential for ziftomenib to address this need," said Eunice Wang, M.D., Chief of the Leukemia Service at Roswell Park Comprehensive Cancer Center and principal investigator of the trial. "NPM1-mutant AML represents approximately 30% of new AML cases annually and is a disease of significant unmet need for which there is no approved targeted therapy. The favorable safety profile and encouraging clinical activity demonstrated by ziftomenib to date offer the potential to transform the standard of care for these AML patients."

About NPM1-mutant AML

AML is the most common acute leukemia in adults and begins when the bone marrow makes abnormal myeloblasts (white blood cells), red blood cells or platelets. Despite the many available treatments for AML, prognosis for patients remains poor and a high unmet need remains. The menin pathway is considered a driver for multiple genetic alterations of the disease, of which NPM1 mutations are among the most common, representing approximately 30% of AML cases. While patients with NPM1-m AML have high response rates to frontline therapy, relapse rates are high and survival outcomes are poor, with only 30% overall survival at 12 months in the R/R setting. Additionally, NPM1 mutations frequently occur with co-mutations in other disease-associated genes, including FLT3, DNMT3A and IDH1/2, with prognosis heavily influenced by the occurrence of co-occurring mutations. Adult patients with NPM1-m AML and select co-mutations and/or R/R disease have a poor prognosis, with median overall survival of only approximately 7.8 months in 2nd line, 5.3 months in 3rd line and 3.5 months following the 4th line.1 There are currently no FDA-approved therapies targeting NPM1-m AML.

About Ziftomenib

Ziftomenib is a novel, once-daily, oral investigational drug candidate targeting the menin-KMT2A/MLL protein-protein interaction for treatment of genetically defined AML patients with high unmet need. In the KOMET-001 Phase 1 study, ziftomenib demonstrated an encouraging safety profile and tolerability with reported events most often consistent with features and manifestations of underlying disease. Clinical activity of ziftomenib as a monotherapy was optimal at the 600 mg daily dose and a 35% complete remission rate was observed in 20 patients with NPM1-mutant AML treated at the recommended Phase 2 dose (600 mg). Ziftomenib has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration for the treatment of R/R NPM1-mutant AML. Additional information about clinical trials for ziftomenib can be found at kuraoncology.com/clinical-trials/#ziftomenib.

On May 14, 2024 Kintara Therapeutics, Inc. (Nasdaq: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, reported financial results for its fiscal third quarter ended March 31, 2024, and recent corporate developments (Press release, Kintara Therapeutics, MAY 14, 2024, View Source [SID1234643229]).

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Recent Corporate Developments

Announced that Kintara had entered into a definitive merger agreement (the "Merger Agreement") with TuHURA Biosciences, Inc. ("TuHURA"), a Phase 3 registration-stage immune-oncology company developing novel technologies to overcome resistance to cancer immunotherapy, and Kayak Mergeco, Inc., Kintara’s wholly-owned subsidiary, whereby Kayak Mergeco will merge with and into TuHURA with TuHURA surviving the merger and becoming Kintara’s direct, wholly-owned subsidiary(the "Merger"). Pursuant to the terms of the Merger, stockholders of TuHURA will receive shares of Kintara common stock. Kintara’s existing stockholders will receive contingent value rights ("CVR"), entitling them to receive shares of common stock upon achievement of enrollment of a minimum of 10 patients in the REM-001 study, with such patients each completing 8 weeks of follow-up on or before December 31, 2025. Under the terms of the Merger Agreement, on a pro forma basis, Kintara’s stockholders post-Merger are expected to collectively own approximately 2.85%, or approximately 5.45% including the shares underlying the CVR if the milestone is achieved, of the common stock of the post-Merger combined company on a fully-diluted basis. The transaction is expected to close in the third quarter of 2024. (April 2024)

Announced the expansion of the inclusion criteria in the open label 15-patient REM-001 study in cutaneous metastatic breast cancer (CMBC) to include patients receiving pembrolizumab (KEYTRUDA) for at least three months at screening. (March 2024)

Announced the initiation of an open label 15-patient study in CMBC patients which is evaluating REM-001, a second-generation photodynamic therapy (PDT) photosensitizer agent, and is designed to test the 0.8 mg dose as well as optimize the study design in advance of a Phase 3 trial initiation. The primary endpoint in the study is Best Overall Objective Response Rate (bORR) (complete response or partial response) of the target treatment fields at any time from treatment up to, and including, week 24. The majority of the costs to run this study will be covered by the $2.0 million Small Business Innovation Research (SBIR) grant Kintara was awarded from the National Institutes of Health (NIH). (February 2024)

Announced that Kintara received a letter from The Nasdaq Stock Market LLC stating it had regained compliance with Nasdaq’s minimum stockholders’ equity requirement. (February 2024)
Summary of Financial Results for Fiscal Year 2023 Third Quarter Ended March 31, 2024

As of March 31, 2024, Kintara had cash and cash equivalents of approximately $6.35 million.

For the three months ended March 31, 2024, Kintara reported a net loss of approximately $2.0 million, or $0.05 per share, compared to a net loss of approximately $3.3 million, or $1.94 per share, for the three months ended March 31, 2023. The decreased net loss for the three months ended March 31, 2024, compared to the three months ended March 31, 2023, was largely attributed to lower research and development expenses which was primarily due to lower clinical development costs. General and administrative costs were higher during the same period primarily due to an increase in professional fees related to the proposed transaction with TuHURA.

Selected Balance Sheet Data (in thousands)

March 31,
2024

June 30,
2023

$

$

Cash and cash equivalents

6,351

1,535

Working capital

5,414

188

Total assets

7,446

3,979

Total stockholders’ equity

5,922

731

Selected Statement of Operations Data (in thousands, except per share data)

For the three months ended

March 31,

March 31,

2024

2023

$

$

Research and development

592

2,005

General and administrative

1,493

1,297

Other loss (income)

(74)

(38)

Net loss for the period

(2,011)

(3,264)

Series A Preferred cash dividend

(2)

(2)

Net loss for the period attributable to common stockholders

(2,013)

(3,266)

Basic and fully diluted weighted average number of shares

44,562

1,681

Basic and fully diluted loss per share

(0.05)

(1.94)

For the nine months ended

March 31,

March 31,

2024

2023

$

$

Research and development

2,562

7,235

General and administrative

3,054

4,212

Other loss (income)

(70)

(133)

Net loss for the period

(5,996)

(11,314)

Series A Preferred cash dividend

(6)

(6)

Series C Preferred stock dividend

(173)

(362)

Net loss for the period attributable to common stockholders

(6,175)

(11,682)

Basic and fully diluted weighted average number of shares

16,772

1,596

Basic and fully diluted loss per share

(0.37)

(7.32)

Kintara’s financial statements as filed with the U.S. Securities Exchange Commission can be viewed on the Company’s website at: View Source