On November 7, 2024 Nkarta, Inc. (Nasdaq: NKTX), a clinical-stage biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported financial results for the third quarter ended September 30, 2024 (Press release, Nkarta, NOV 7, 2024, View Source [SID1234647941]).

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"We’re encouraged by the early progress that we’ve made in the clinical investigation of NKX019 for autoimmune disease," said Paul J. Hastings, CEO of Nkarta. "Having dosed a first patient in both Ntrust-1 and the Columbia University Irving Medical Center IST, our learnings can help us optimize the execution of our current and future clinical trials. This includes our Ntrust-2 trial, which is on track to initiate enrollment later this year. Safety and accessibility are paramount in autoimmune disease, and we believe that an off-the-shelf, engineered NK cell therapy has the greatest potential to help patients."

Hastings continued, "We have decided to forgo future development of NKX019 in non-Hodgkin lymphoma. In reviewing the clinical data from the latest cohort of patients with large B-cell lymphoma and the evolving treatment landscape, Nkarta will focus its efforts on autoimmune diseases, where we believe NKX019 has potential to transform patient care."

Clinical development of NKX019 for autoimmune diseases advances

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Dosing of the first patient in Ntrust-1, a clinical trial of NKX019 for the treatment of lupus nephritis. As previously announced, the first Ntrust-1 patient entered screening in June 2024.

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Dosing of the first patient in the IST of NKX019 in systemic lupus erythematosus at Columbia University Irving Medical Center (CUIMC). As previously announced, the CUIMC IST was initiated in July 2024.
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Both studies continue to enroll participants.

Anticipated autoimmune milestones 2024-2025

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Initiation of patient enrollment expected by year-end 2024 in Ntrust-2, a clinical trial of NKX019 for the treatment of systemic sclerosis, myositis and vasculitis. As previously announced, the Investigational New Drug (IND) Application for Ntrust-2 cleared in June 2024.
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Preliminary clinical data from Ntrust-1 and Ntrust-2 clinical trials planned for 2025.

Update for NKX019 in non-Hodgkin lymphoma (NHL)

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A cohort of seven patients with heavily pretreated large B-cell lymphoma (LBCL) whose disease progressed following treatment with a CD19 CAR T-cell therapy received NKX019 on Days 0, 3, and 7 following lymphodepletion.
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There were no cases of Grade >2 cytokine release syndrome (CRS) and no cases of immune effector cell-associated neurotoxicity (ICANS).
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Five patients achieved a partial response after a first cycle of treatment. One of these five patients achieved a complete response with >6 months durability after receiving a second cycle of treatment.
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Nkarta aims to report final data from the LBCL cohort at a future medical conference.
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Nkarta will forgo further development in NHL and prioritize development efforts on autoimmune diseases.

Third Quarter 2024 and Recent Financial Highlights

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Nkarta had cash, cash equivalents, restricted cash, and investments in marketable securities of $405.3 million as of September 30, 2024.
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Research and development (R&D) expenses were $25.3 million for the third quarter of 2024. Non-cash stock-based compensation expense included in R&D expense was $1.8 million for the third quarter of 2024.
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General and administrative (G&A) expenses were $8.5 million for the third quarter of 2024. Non-cash stock-based compensation expense included in G&A expense was $2.3 million for the third quarter of 2024.
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Net loss was $28.3 million, or $0.39 per basic and diluted share, for the third quarter of 2024. This net loss includes non-cash charges of $5.8 million that consisted primarily of share-based compensation and depreciation expenses.

Financial Guidance

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Nkarta expects its current cash and cash equivalents will be sufficient to fund its current operating plan into late 2027.

About NKX019

NKX019 is an allogeneic, cryopreserved, off-the-shelf immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy adult donors. It is engineered with a humanized CD19-directed CAR for enhanced cell targeting and a proprietary, membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support. CD19 is a biomarker for normal B cells as well as those implicated in autoimmune disease and B cell-derived malignancies.

About Ntrust Clinical Trials in Autoimmune Disease

Ntrust-1 and Ntrust-2 are multi-center, open label, dose escalation clinical trials that build on academic studies of durable, drug-free remissions in patients with autoimmune disease after CD19-targeted cell therapy. Both trials will assess the safety of NKX019 in people living with autoimmune diseases as well as its ability to enable long-term remissions via a "reset" of the immune system through the elimination of pathogenic B cells. Per the trial protocols, patients receive three-dose cycles of NKX019 at 1 billion or 1.5 billion cells per dose following single-agent lymphodepletion with cyclophosphamide, an agent with an established safety profile across autoimmune diseases. Leveraging the engineering of NKX019, no patients in either trial will receive supplemental cytokines or antibody-based therapeutics. This approach is designed to evaluate the single-agent activity of NKX019 and facilitate a more rapid path to regulatory approval.

In the Ntrust-1 study (NCT06557265), patients with refractory lupus nephritis receive three-dose cycles of NKX019 following lymphodepletion. Patients in Ntrust-1 may also receive additional cycles to restore response.

Once initiated, Ntrust-2 will enroll patients with systemic sclerosis (scleroderma), idiopathic inflammatory myopathy (myositis), and ANCA-associated vasculitis into parallel cohorts, and NKX019 will be dosed on Days 0, 3, and 7, a regimen that may be advantageous across all Nkarta clinical trials. Each trial is designed to initially enroll up to 12 patients.

About the Investigator-Sponsored Clinical Trial of NKX019 for Systemic Lupus Nephritis

The single-center, single-arm, open-label Phase 1 investigator-sponsored clinical trial is designed to enroll up to 6 patients with systemic lupus erythematosus, regardless of renal involvement, and will evaluate safety and clinical outcomes in a potentially different population than Ntrust-1. Translational and biomarker studies, including autoantibodies, cytokine profiles and pharmacokinetics are also planned. Patients receive NKX019 following single-agent lymphodepletion with cyclophosphamide. The clinical trial is being led by Anca D. Askanase, M.D., M.P.H., Director, Lupus Center at Columbia University Irving Medical Center and the Director of Rheumatology Clinical Trials.

On November 7, 2024 Rezolute, Inc. (Nasdaq: RZLT) ("Rezolute" or the "Company"), a late-stage biopharmaceutical company dedicated to developing transformative therapies for rare diseases with serious unmet needs, reported financial results and provided a business update for the three months ended September 30, 2024 (Press release, Rezolute, NOV 7, 2024, View Source [SID1234647969]).

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"Execution across our two Phase 3 programs in patients with congenital HI and tumor HI will be the focus going into 2025," said Nevan Elam, Chief Executive Officer and Founder of Rezolute. "We are pleased with the progress we’ve made in sunRIZE enrollment and look forward to advancing our Phase 3 study in tumor HI patients based on the success demonstrated in our Expanded Access Program. As a rare disease company with two late-stage clinical trials, we recognize how critical 2025 will be in progressing our programs in order to provide a potentially meaningful therapy for patients where limited options currently exist."

Recent Pipeline Progress and Anticipated Milestones

Congenital HI

· Ex-U.S. patient enrollment in sunRIZE, a global, pivotal Phase 3 clinical study for ersodetug in patients with congenital HI, is on track.
· Study start-up activities are underway for enrollment of U.S. participants in early 2025.
· Topline results from sunRIZE expected in the second half of 2025.

Tumor HI

· Start-up activities are progressing for the Phase 3 registrational study for ersodetug in patients with tumor HI.
· Patient enrollment anticipated to begin in the first half of 2025.
· Topline results expected in the second half of 2026.

Fiscal First Quarter Financial Results

Cash, cash equivalents and investments in marketable securities were $117.8 million as of September 30, 2024, compared to $127.1 million as of June 30, 2024.

Research and development expenses were $12.8 million for the first quarter of fiscal 2025, compared with $12.2 million for the same period a year ago, with the increase primarily attributable to increased expenditures in clinical trial activities, manufacturing costs and higher personnel-related expenses, which include employee compensation.

General and administrative expenses were $4.2 million for the first quarter of fiscal 2025, compared with $3.7 million for the same period a year ago, with the increase primarily attributable to professional fees and employee-related expenses as a result of increased headcount.

Net loss was $15.4 million for the first quarter of fiscal 2025 compared with a net loss of $14.5 million for the same period a year ago.

About Ersodetug

Ersodetug is a fully human monoclonal antibody that binds to a unique allosteric site on insulin receptors to counteract the effects of insulin receptor over-activation by insulin and related substances (such as IGF-2), thereby improving hypoglycemia in the setting of hyperinsulinism (HI). Because ersodetug acts downstream from the pancreas, it has the potential to be universally effective at treating hypoglycemia due to any form of HI.

About sunRIZE

The Phase 3 sunRIZE study is a multi-center, randomized, double-blind, placebo-controlled, parallel arm study designed to evaluate the efficacy and safety of ersodetug in patients with congenital HI who are experiencing poorly controlled hypoglycemia. Participants between the ages of 3 months to 45 years old are eligible to participate. The study is enrolling up to 56 participants in more than a dozen countries around the world.

On November 7, 2024 BPGbio, Inc., a leading biology-first, AI-powered clinical-stage biopharma company focused on mitochondrial biology and protein homeostasis, reported that it will present three scientific posters at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2024 Annual Meeting, taking place November 6-10, 2024, in Houston, Texas (Press release, BPGbio, NOV 7, 2024, View Source [SID1234647992]). The posters will highlight the latest research on the company’s drug candidates BPM31510 and BRG399 in the immuno-oncology space, providing further validation and paving the way for new potential therapeutic strategies in cancer treatment.

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In the first study, titled "The Anti-tumor Response of BPM31510 is Associated with Immune Cell Regulation in the Tumor Microenvironment," researchers showed that BPM31510 significantly increases reactive oxygen species (ROS) levels in cancer cells, leading to cell death across multiple cancer types. They also identified that, BPM31510 can boost the activity of cytotoxic tumor-infiltrating lymphocytes and reduce markers of T cell exhaustion. This dual action gives it the potential to be especially effective in treating "immunologically cold" tumors, such as glioblastoma and pancreatic cancer.

The second study, titled "BRG399, a Novel Oral Microtubule Binding Agent, Induces Tumor Regression and Immune Memory in an Orthotopic Glioblastoma Rat Model," found that BRG399 treatment leads to glioblastoma tumor regression, with 100% survival in treated rats. BRG399 also induces an immune memory response, preventing the recurrence of tumors when surviving rats are re-challenged with glioma cancer cells.

The third study, titled, "BRG399, a Novel Oral Microtubule Binding Agent, Exhibits Immune-Modulatory Properties Enhancing Anti-Tumor Responses," showed that BRG399 alters the immune cell composition within the tumor microenvironment and blood. BRG399 also reduced markers of T cell exhaustion, suggesting that it can reinvigorate immune responses against tumors. These findings suggest that BRG399 should be further investigated as a potential component of cancer therapy, particularly when combined with immunotherapies, as it can both kill cancer cells and enhance immune activity.

"These compounds – BPM31510 and BRG399 – push the boundaries of what’s possible in cancer therapy, showing that we can not only attack the tumor but also empower the body’s immune system to keep fighting long after the treatment ends," said Stephane Gesta, Ph.D., VP, Discovery and Translational Biology at BPGbio. "As we advance BRG399 through preclinical trials and approach the completion of BPM31510’s Phase 2b study, we will continue leveraging our NAi Interrogative Biology Platform to gain additional insight for exploring new therapeutic opportunities for other diseases."

Poster Presentation Details:

The Anti-Tumor Response of BPM31510 Is Associated with Immune Cell Regulation in the Tumor Microenvironment
Date and Time: November 8, 2024, 1:00 p.m. CST
Location: Exhibit Halls A B, George R. Brown Convention Center, Houston, Texas
Presenter: Maria-Dorothea Nastke, Ph.D.
Abstract Number: 1312

BRG399, a Novel Oral Microtubule Binding Agent, Induces Tumor Regression and Immune Memory in an Orthotopic Glioblastoma Rat Model
Date and Time: November 9, 2024, 2:00 p.m. CST
Location: Exhibit Halls A B, George R. Brown Convention Center, Houston, Texas
Presenter: Maria-Dorothea Nastke, Ph.D.
Abstract Number: 1313

BRG399, a Novel Oral Microtubule-Binding Agent, Exhibits Immune-Modulatory Properties Enhancing Anti-Tumor Responses
Date and Time: November 9, 2024, 3:00 p.m. CST
Location: Exhibit Halls A B, George R. Brown Convention Center, Houston, Texas
Presenter: Kaila Bennett, Ph.D.
Abstract Number: 1284
About BPM31510

BPM31510 is BPGbio’s lead candidate in late-stage development for glioblastoma multiforme (GBM) and pancreatic cancer. The compound has demonstrated a tolerable safety profile and shown potential clinical benefit in both populations. The mechanism of action of BPM31510 was first validated by data from BPGbio’s NAi Interrogative Biology platform, which suggested that there is a hallmark shift in the tumor microenvironment (TME) induced by BPM31510 which modulates mitochondrial oxidative phosphorylation in highly aggressive tumors. BPGbio has received FDA’s Rare Pediatric Disease Designation for BPM31510IV for primary CoQ10 deficiency and BPM31510T for Epidermolysis Bullosa (EB) .

About BRG399

BRG399 is a BPGbio-developed candidate being studied for its therapeutic potential as a treatment for solid and liquid tumor cancers as well as diseases associated with neutrophil-driven inflammation. This experimental drug, a first-in-class, anti-tubulin agent with broad-spectrum anti-cancer activity and favorable pharmacological properties including oral bioavailability for clinical testing. BRG399 is leading the new oncology drug pipeline for BPGbio among other drug candidates which uniquely target the colchicine binding pocket in tubulin.

On November 7, 2024 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, reported its business update and financial position for the quarter ending September 30, 2024 (Press release, Transgene, NOV 7, 2024, View Source [SID1234655851]).

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Key events and upcoming milestones
TG4050: Neoantigen therapeutic cancer vaccine
Transgene and NEC will present promising new data from the ongoing randomized Phase I trial of the neoantigen individualized therapeutic cancer vaccine, TG4050 at SITC (Free SITC Whitepaper) 2024 on November 9, 2024 (see press release here). These data provide robust clinical proof of principle for Transgene’s lead candidate in the adjuvant head and neck cancer setting, a patient population at high risk of relapse.

Compelling 24.1-month median follow-up data presented showed that all 16 patients treated with TG4050 after completion of adjuvant standard of care remain disease-free and have not relapsed, comparing favorably to the observational arm which saw 3 out of 16 patients relapse. All patients treated with TG4050 developed specific immune responses against the selected personalized antigen targets, demonstrating the strong immunogenicity of the cancer vaccine, with both de novo and amplified responses. Additionally, immune responses are sustained over a 7-month period, covering the induction and boost periods.

In Q2 2024, Transgene started enrolling patients in the Phase II part of the expanded randomized Phase I/II trial investigating TG4050 in the adjuvant treatment of head and neck cancer (NCT04183166). Patient enrollment continues to progress at a good pace.

TG4050 is the only individualized neoantigen cancer vaccine currently being developed in a randomized trial in the adjuvant treatment of head and neck cancer.

TG4050 has potential applicability across a range of solid tumors where there remains a significant unmet medical need, despite the existing therapeutic options, including immunotherapies. As a result, Transgene is conducting preliminary work on a potential new Phase I trial in a further undisclosed indication.

TG4001 – Shared antigen cancer vaccine
In October 2024, Transgene announced that its randomized Phase II study evaluating TG4001 in combination with avelumab versus avelumab alone in patients with recurrent or metastatic HPV16- positive cervical and anogenital tumors did not meet its primary objective (improvement in progressionfree survival).

However, analysis of a pre-planned subgroup showed a positive efficacy trend in favor of the TG4001 containing regimen in cervical cancer patients, which requires further confirmation through additional analyses, including by PD-L1 status. These patients account for approximately half of the patients enrolled in the study. Transgene is currently evaluating the full study results in detail to determine the best way forward for this program and will communicate further once this is completed.

Oncolytic Viruses
BT-001 (intratumoral administration):
In September 2024, Transgene and its partner BioInvent presented preliminary Phase I/IIa data (NCT04725331) at ESMO (Free ESMO Whitepaper) (see press release here) showing that BT-001 induced tumor regression in patients unresponsive to prior anti PD(L)-1 treatment, both as monotherapy and in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab).

BT-001 replicated in the tumor and expressed the encoded GM-CSF and anti-CTLA-4 transgenes. Notably, BT-001 in combination with pembrolizumab showed first signs of efficacy in 2 out of 6 patients, with shrinkage of injected and non-injected lesions. In a reported case study, BT-001 treatment was able to modulate the tumor microenvironment, converting "cold tumors" into "hot tumors", and inducing T cell infiltration.

Transgene and BioInvent are finalizing the second cohort in the part B of the Phase I/IIa trial, to inform on the further development strategy.

TG6050 (intravenous administration):
The Phase I Delivir trial (NCT05788926), evaluating TG6050 in patients with advanced non-small cell lung cancer who have failed standard therapeutic options, completed the first two dose levels. Dose-limiting toxicity was observed in one patient in the third cohort and additional patients are being enrolled according to the protocol to complete this trial. Initial data are now expected in H1 2025.

Preclinical data, recently published in the Journal for ImmunoTherapy of Cancer (JITC), were awarded with the JITC Best Oncolytic and Local Immunotherapy Paper Award. The article on TG6050 demonstrates that it induces tumor regression in numerous "hot" and "cold" murine tumor models investigated in these studies. This antitumoral activity was further amplified when TG6050 was combined with an immune checkpoint inhibitor (article available here).

Cash, cash equivalents and other financial assets
Cash, cash equivalents and other financial assets stood at €14.0 million as of September 30, 2024, compared to €15.7 million as of December 31, 2023.

In the first nine months of 2024, Transgene’s cash burn amounted to €31.3 million compared to a cash burn of €13.8 million in the same period of 2023. The difference is explained by the July 2023 sale of Transgene’s remaining shares held in Tasly BioPharmaceuticals for a total amount of US$15.3 million (€14.3 million).

At of the end of July 2024, Transgene announced the conversion into shares of €33 million debt drawn down from the current account advance granted by the Company’s major shareholder TSGH (Institut Merieux), in accordance with the terms of an agreement signed for the first time in 2023. As a result, the share capital of Transgene held by TSGH increased from 59.7% to 69.1% of the outstanding shares. In carrying out this transaction, Transgene has strengthened its balance sheet, reduced its debt levels and its debt burden as a result of lower interest payments.

As of September 30, 2024, Transgene had the capacity to draw down €23.5 million from the current account advance provided by TSGH.

Transgene confirms financial visibility into Q4 2025, enabling the Company to deliver news flow on its portfolio progress over the next 12 months.

On November 7, 2024 Onchilles Pharma, a private biotech company pioneering pan-cancer therapeutics that leverage the ELANE pathway, reported the presentation of new preclinical data from its NEU-002 program at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Onchilles Pharma, NOV 7, 2024, View Source [SID1234647942]). The event is being held virtually and at the George R. Brown Convention Center in Houston, Texas from November 6-10, 2024.

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The ELANE pathway is a novel innate immune mechanism that enables potent and selective immunogenic cell death of cancer cells irrespective of immunotype, genotype, anatomical origin while sparing healthy tissue. Onchilles Pharma has leveraged this pathway to develop N17350 and NEU-002, two leading therapeutic candidates designed for intratumoral and intravenous (IV) administration, respectively. N17350 is on track to start Phase 1 clinical trials in 2025 to validate the ELANE pathway in head & neck, skin, breast, and lung cancers.

At SITC (Free SITC Whitepaper) 2024, Onchilles Pharma presented new preclinical data on NEU-002, which allows targeting the ELANE pathway through systemic delivery. NEU-002 addresses the challenges of systemic delivery by overcoming inhibition from serine protease inhibitors and enhancing substrate specificity, thereby extending its potential to treat a broad range of solid tumor types that are well-suited for systemic administration.

Key Preclinical Data Highlights:

Enhanced Specificity and Activity: NEU-002 retains full enzymatic activity in plasma and shows improved substrate specificity, effectively cleaving CD95, its therapeutic target, while sparing known off-target substrates.
Selective Cancer Cell Killing: The NEU-002 candidates selectively induce immunogenic cell death in primary cancer cells derived from ovarian cancer patients, validating their selective killing properties in primary human tissue.
Durable Responses: In preclinical studies using the CT26 tumor mouse model, NEU-002 treatment generated complete responses with resistance to tumor rechallenge, suggesting the potential for immune memory formation.
"The data presented today mark a significant advancement in the systemic targeting of the ELANE pathway," said Lev Becker, Ph.D., Scientific Founder and Chief Scientific Officer of Onchilles Pharma. "The ability to selectively target cancer cells while inducing a sustained immune response could provide durable clinical benefits across a wide range of tumor types."

Court R. Turner, J.D., Co-Founder & Chief Executive Officer, added, "N17350 and NEU-002 represent a transformative approach in oncology, with the potential to redefine the standard of care. We are excited about advancing N17350 into a Phase 1 trial in 2025, providing the clinical proof-of-concept for targeting the ELANE pathway and delivering innovative cancer treatments to patients."

To download the poster, click here.

About the NEU-002 Program and the ELANE Pathway

Onchilles Pharma’s NEU-002 program stems from groundbreaking research by its scientific founder, Dr. Lev Becker, who identified the ELANE pathway as a novel innate immune mechanism where neutrophil elastase (ELANE) selectively kills cancer cells while sparing healthy cells. Published in Cell in 2021, these findings have laid the foundation for developing NEU-002, which is tailored for systemic IV delivery, and N17350, designed for intratumoral administration. By leveraging the ELANE pathway, these candidates offer a unique approach to treat cancer regardless of genetic background, anatomical origin, or immunotype, positioning them as potential game-changers in cancer therapy.

Looking Ahead: Clinical Validation in 2025

Onchilles Pharma plans to initiate a Phase 1 trial of its lead candidate, N17350, in 2025 to validate the ELANE pathway in humans. This trial will further explore the safety and efficacy of this innovative mechanism, representing a significant step toward realizing the potential of ELANE-based therapies.