On November 7, 2024 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported financial results for the third quarter ended September 30, 2024 (Press release, Puma Biotechnology, NOV 7, 2024, View Source [SID1234647945]). Unless otherwise stated, all comparisons are for the third quarter of 2024 compared to the third quarter of 2023.

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Product revenue, net consists entirely of sales revenue from NERLYNX, Puma’s first commercial product. Product revenue, net in the third quarter of 2024 was $56.1 million, compared to $51.6 million in the third quarter of 2023. Product revenue, net in the first nine months of 2024 was $140.8 million, compared to $149.9 million in the first nine months of 2023.

Based on accounting principles generally accepted in the United States (GAAP), Puma reported net income of $20.3 million, or $0.41 per basic and diluted share, for the third quarter of 2024, compared to a net income of $5.8 million, or $0.12 per basic and diluted share, for the third quarter of 2023. Net income for the first nine months of 2024 was $11.0 million, or $0.23 per basic share and $0.22 per diluted share, compared to net income of $9.3 million, or $0.20 per basic and diluted share, for the first nine months of 2023.

Non-GAAP adjusted net income was $22.4 million, or $0.46 per basic share and $0.45 per diluted share, for the third quarter of 2024, compared to $8.3 million, or $0.18 per basic share and $0.17 per diluted share, for the third quarter of 2023. Non-GAAP adjusted net income for the first nine months of 2024 was $17.5 million, or $0.36 per basic and diluted share, compared to non-GAAP adjusted net income of $17.1 million, or $0.36 per basic and diluted share, for the first nine months of 2023. Non-GAAP adjusted net income excludes stock-based compensation expenses. For a reconciliation of GAAP net income to non-GAAP adjusted net income and GAAP net income per share to non-GAAP adjusted net income per share, please see the financial tables at the end of this news release.

Net cash provided by operating activities for the third quarter of 2024 was $11.0 million, compared to $10.7 million in the third quarter of 2023. Net cash provided by operating activities for the first nine months of 2024 was $23.3 million, compared to net cash provided by operating activities of $16.6 million in the first nine months of 2023. On September 30, 2024, Puma had cash, cash equivalents and marketable securities of approximately $97 million, compared to cash, cash equivalents, and marketable securities of approximately $96 million at December 31, 2023.

"We are pleased to announce both positive net income and positive operating cash flow for the third quarter of 2024," said Alan H. Auerbach, Chairman, Chief Executive Officer, and President of Puma. "In addition to our focus on the commercialization of NERLYNX, we are also continuing to make progress with the clinical development of alisertib for patients with extensive stage small cell lung cancer and patients with chemotherapy-naïve HER2-negative, hormone receptor-positive metastatic breast cancer."

Mr. Auerbach added, "We anticipate the following key milestones over the next 12 months: (i) initiation of ALI-1201/ALISCA-Breast1, a Phase II trial of alisertib in combination with endocrine treatment in patients with chemotherapy-naïve HER2-negative, hormone receptor-positive metastatic breast cancer (Q4 2024); (ii) presentation of interim data from ALI-4201/ALISCA-Lung1, a Phase II clinical trial of alisertib monotherapy for the treatment of patients with extensive stage small cell lung cancer (2025); and (iii) presentation of interim data from ALISCA-Breast1, a Phase II trial of alisertib in combination with endocrine treatment in patients with chemotherapy-naïve HER2-negative, hormone receptor-positive metastatic breast cancer (2025)."

Revenue

Total revenue consists of product revenue, net from sales of NERLYNX, Puma’s first commercial product and royalty revenue. For the third quarter of 2024, total revenue was $80.5 million, of which $56.1 million was product revenue, net and $24.4 million was royalty revenue. This compares to total revenue of $56.1 million in the third quarter of 2023, of which $51.6 million was product revenue, net and $4.5 million was royalty revenue. For the first nine months of 2024, total revenue was $171.4 million, of which $140.8 million was product revenue, net and $30.6 million was royalty revenue. This compares to total revenue of $163.5 million for the first nine months of 2023, of which $149.9 million was product revenue, net, and $13.6 million was royalty revenue.

Operating Costs and Expenses

Total operating costs and expenses were $58.4 million for the third quarter of 2024, compared to $47.5 million for the third quarter of 2023. Operating costs and expenses in the first nine months of 2024 were $153.8 million, compared to $145.7 million in the first nine months of 2023.

Cost of Sales

Cost of sales was $29.1 million for the third quarter of 2024, compared to $13.3 million for the third quarter of 2023. Cost of sales was $50.5 million for the first nine months of 2024, compared to $38.4 million for the first nine months of 2023. The increase was primarily due to royalty expense related to the timing of sales made in China by our sub-licensee and an increase in units shipped to China.

Selling, General and Administrative Expenses

Selling, general and administrative (SG&A) expenses were $16.8 million for the third quarter of 2024, compared to $22.8 million for the third quarter of 2023. SG&A expenses for the first nine months of 2024 were $63.5 million, compared to $69.7 million for the first nine months of 2023. The $6.2 million decrease in SG&A expenses for the first nine months of 2024 compared to the first nine months of 2023 resulted from a decrease in payroll and related costs of approximately $2.4 million, primarily due to lower headcount, partially offset by annual salary increases; and a decrease in professional fees and expenses of approximately $1.2 million, primarily due to decreases of approximately $3.2 million in marketing expenses and $0.4 million in insurance and other expenses. These decreases were partially offset by an increase of approximately $2.3 million in legal fees; a decrease in stock-based compensation expense of approximately $1.1 million, primarily due to lower headcount; a decrease in provision for credit loss of $0.6 million, due to a customer payment on an overdue receivable; and a decrease in loss on impairment of asset expense of approximately $0.6 million in connection with our decision to sublease a portion of our office space in 2023.

Research and Development Expenses

Research and development (R&D) expenses were $12.5 million for the third quarter of 2024, compared to $11.4 million for the third quarter of 2023. R&D expenses for the first nine months of 2024 were $39.8 million, compared to $37.6 million for the first nine months of 2023. The $2.2 million year-over-year increase in R&D expenses resulted primarily from an increase in clinical trial expenses of approximately $1.8 million, primarily due to the procurement of alisertib drug product and increased alisertib study activity, partially offset by fewer clinical milestones being achieved, and an increase in internal R&D expenses of approximately $0.8 million, primarily due to one-time payroll and severance related expenses.

Total Other Income (Expenses)

Total other expenses were $1.5 million for the third quarter of 2024, compared to $2.6 million for the third quarter of 2023. Total other expenses of $5.7 million for the first nine months of 2024 were down from $8.0 million for the first nine months of 2023 due primarily to an increase in interest income.

Fourth Quarter and Full Year 2024 Financial Outlook

Fourth Quarter 2024

Full Year 2024 (previous)

Full Year 2024 (new)

Net Product Revenue

$46–$48 million

$183–$190 million

$187–$190 million

Royalty Revenue

$3.5–$5 million

$30–$34 million

$34–$36 million

License Revenue

$1–$2 million

$1–$2 million

$1–$2 million

Net Income

$4–$6 million

$12–$15 million

$15–$17 million

Gross to Net Adjustment

21%–22%

21%–22%

20.5%–21.5%

Conference Call

Puma Biotechnology will host a conference call to report its third quarter 2024 financial results and provide an update on Puma’s business and outlook at 1:30 p.m. PST/4:30 p.m. EST on Thursday, November 7, 2024. The call may be accessed by dialing 1 (877) 709-8150 (domestic) or 1 (201) 689-8354 (international). Please dial in at least 10 minutes in advance and inform the operator that you would like to join the "Puma Biotechnology Conference Call." A live webcast of the conference call and presentation slides may be accessed on the Investors section of the Puma Biotechnology website at View Source A replay of the call will be available shortly after completion of the call and will be archived on Puma’s website for 90 days.

On November 7, 2024 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage allogeneic cell therapy and genetic medicines company advancing differentiated non-viral treatments for patients with cancer, autoimmune and rare diseases, reported updates and financial results for the third quarter ended September 30, 2024 (Press release, Poseida Therapeutics, NOV 7, 2024, View Source [SID1234647944]).

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"Poseida continues to make excellent progress across all of our key initiatives, highlighted by compelling data presentations from our pipeline of innovative, non-viral allogeneic cell therapy and genetic medicine programs, the expansion and advancement of our collaborations with Roche and Astellas, and our science-backed strategy to apply our platform to the large and growing opportunity for CAR-T in autoimmune diseases," said Kristin Yarema, Ph.D., President and Chief Executive Officer of Poseida Therapeutics. "As a result, we have generated $130 million in non-dilutive, partnership related milestones and payments so far this year, along with $49 million earned through R&D expense reimbursements. This has resulted in Poseida being cash flow positive for the first nine months of the year and extended our cash runway, with additional upside potential from continued execution, clinical progress and business development. We look forward to sharing updates on our CAR-T programs at our upcoming Cell Therapy R&D Day and future medical meetings."

Recent Accomplishments

Cell Therapy

Expanded strategic global collaboration with Roche, including ongoing pipeline progress and the nomination of a new dual CAR-T development candidate.

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The new candidate is an allogeneic, dual CAR-T therapy targeting known antigens expressed in hematologic malignancies, including multiple myeloma. Poseida and Roche now have three programs under their collaboration, including P-BCMA-ALLO1, an allogeneic CAR-T therapy in Phase 1/1b development for multiple myeloma, and P-CD19CD20-ALLO1, an allogeneic dual CAR-T candidate in Phase 1 development for B-cell malignancies. Roche has the option to nominate additional development candidates in the future.
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P-BCMA-ALLO1 continues to be positioned as a leading clinical-stage allogeneic CAR-T therapy with a compelling and differentiated profile: interim Phase 1 data presented at the International Myeloma Society (IMS) annual meeting in September showed a 91% overall response rate (ORR) in an optimized lymphodepletion arm, including a 100% ORR in B-cell maturation antigen (BCMA)-naïve patients, and an 86% ORR in those who had received at least one prior BCMA- and/or G protein-coupled receptor class C group 5 member D (GPRC5D)-targeting treatment modality, along with differentiated safety results with no dose-limiting toxicities, low rates of cytokine release syndrome (CRS) and immune effector cell neurotoxicity syndrome (ICANS) all Grade 2 or less and no graft vs. host disease or Parkinsonism. No anti-myeloma bridging therapy or prophylaxis with steroids or tocilizumab, no invasive apheresis or manufacturing wait with average time from treatment decision to clinical response of only 3.5 weeks1 (median time to response of 16 days post initial P-BCMA-ALLO1 therapy). The patients in this study had more advanced disease than the myeloma patients studied in clinical trials of approved autologous CAR-T therapies2, and in the intent-to-treat population, 100% of patients were infused with P-BCMA-ALLO1.
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Poseida’s conference call to discuss IMS data featured a fireside chat with leading myeloma experts that highlighted key aspects of the data and provided context on current treatment approaches. The experts highlighted that off-the-shelf availability allows patients to start therapy fast, without need for bridging therapy commonly required by autologous CAR-T, and in some cases, offers a solution for patients who are ineligible for autologous treatments; rapid clinical responses; attractive safety profile; ability to treat patients on an outpatient basis; and ability to treat BCMA-exposed patients as key benefits observed in the trial.
•
P-BCMA-ALLO1 development continues, with ongoing patient enrollment in the recently initiated Phase 1/1b trial that is using the same lymphodepletion regimen as the optimized lymphodepletion arm described above, including two different cell doses. During the third quarter, P-BCMA-ALLO1 was granted Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration (FDA) to treat relapsed/refractory multiple myeloma after three or more prior lines of therapies including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.
•
Poseida has secured $80 million from Roche collaboration milestones to-date in 2024, including a milestone payment received in the third quarter related to the initiation of the P-BCMA-ALLO1 Phase 1b clinical trial, and an additional payment for the nomination of the new development candidate in October.

Progressed the strategic research collaboration and license agreement with Astellas’ wholly owned subsidiary Xyphos Biosciences with the formal nomination of the second high potential program target. Both program targets nominated under the collaboration are well-known and validated solid tumor targets.

Accelerating highly differentiated dual targeting allogeneic CAR-T for autoimmune disease with P-BCMACD19-ALLO1 as first pipeline candidate to address this significant market opportunity. P-BCMACD19-ALLO1 is an allogeneic dual CAR-T candidate currently in IND-enabling studies. We believe targeting BCMA and CD19 could provide the potential to enable more complete immune cell depletion than CAR-Ts targeting only one of the antigens, and that targeting BCMA specifically could provide the potential to deplete autoantibodies from plasma cells, which are believed to be a key driver in many autoimmune diseases and not addressed by targeting CD19 alone. Emerging data from an autologous dual CAR-T targeting BCMA and CD19 has thus far substantiated this dual targeting approach. P-BCMACD19-ALLO1 is also positioned to provide the access benefits of an allogeneic product and a potentially attractive safety profile derived from Poseida’s non-viral TSCM approach and other features unique to the Company’s CAR-T platform, such as its proprietary safety switch.

Strengthened Poseida’s innovation profile and emerging leadership in allogeneic CAR-T with new data at the Society of Hematologic Oncology (SOHO) Twelfth Annual Meeting in September and the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting & Pre-Conference Programs in November.

•
A new case study demonstrating the reactivation of an autologous Poseida CAR-T therapy with a T-cell engager in a patient with relapsed multiple myeloma was presented at SOHO. The patient attained and remains in stringent complete response over 10 months after CAR-T reactivation. This case highlights the potential of Poseida’s TSCM-based CAR-T therapies to deliver a strong anti-myeloma response with long-term remission and CAR-T cell persistence. The Company believes this is the first time that a T-cell engager has been seen to reactivate a CAR-T therapy.
•
New preclinical data highlighting the potential of Poseida’s platform to design and manufacture CAR-TCR-T cells that are rich in stem cell memory T cell (TSCM) and central memory T cells (TCM) for potential use in solid tumors will be presented at SITC (Free SITC Whitepaper) on November 9. In solid tumors, multi-antigens are believed to be necessary for efficacy, and CAR+TCR-T cells can recognize and kill single and double antigen target cells and show the potential to synergize with T-cell engagers. Key highlights from the SITC (Free SITC Whitepaper) presentation include:
o
CAR+TCR-T cells were shown to control single and double antigen-positive tumor growth in vivo, with sustained persistence.
o
T-cell engager was used to re-activate and re-direct engrafted CAR+TCR-T cells to control a secondary tumor challenge expressing different antigens echoing the patient case study presented at SOHO and suggesting an approach to address heterogeneous tumors and/or tumors whose composition evolves over time.

Continued to enroll patients in the Phase 1 clinical trial of P-CD19CD20-ALLO1. In light of the competitive environment for therapies targeting CD19 and CD20, Poseida and Roche anticipate providing initial clinical data from the trial in 2025 once a more complete dataset of the program is available.Genetic Medicines

Demonstrated ongoing leadership in development of non-viral approaches to genetic medicines, supported by data presentation at the American College of Allergy, Asthma & Immunology (ACAAI) 2024 Scientific Meeting featuring P-KLKB1-101, a non-viral, liver-directed genetic medicine that uses the Company’s Cas-CLOVER Site-Specific Gene Editing System. The data showed high-fidelity gene editing at KLKB1 for the targeted correction of hereditary angioedema (HAE), the ability for controlled dose response, favorable tolerability and liver editing approaching the desired therapeutic range. The data reinforce the potential of Cas-CLOVER to be a unique and attractive gene editing tool for a variety of diseases, starting with HAE and KLKB1 editing.

In addition, Poseida had a successful INTERACT meeting with the U.S. FDA for P-FVIII-101 in September 2024. The meeting provided Poseida with early engagement and communication with FDA on the program, in order to support efficient development designed to be aligned with FDA standards. INTERACT meetings focus on innovative and emerging technologies covered by the FDA’s Center for Biologics Evaluation and Research (CBER).

Other Operational Updates and Upcoming Events

Manufacturing Updates

The Company continues to advance its platform process and analytical capabilities for allogeneic cell therapy manufacturing. Recent analytical enhancements have enabled more precise evaluation of prospective donors as well as providing improved characterization of drug product attributes.

Cell Therapy R&D Day

Poseida will host a cell therapy-focused R&D Day on November 14, 2024, to highlight progress and further opportunities across its clinical-stage and earlier-stage pipeline of differentiated allogeneic CAR-T therapies in oncology and autoimmune disease.

The virtual event and access to the live webcast will be available through the following registration link: View Source Registration for this virtual event and access to a replay of the live webcast will also be available on the Investors & Media section of www.poseida.com. A replay of the webcast will be available for approximately 90 days following the presentation.

Financial Results for the Third Quarter 2024

Revenues

Revenues were $71.7 million for the three months ended September 30, 2024, and $125.9 million for the nine months ended September 30, 2024, compared to $9.4 million and $39.7 million for the same periods in 2023, respectively. The increases were primarily due to milestone recognition and an increase in reimbursed research and development expenses under the Roche Collaboration Agreement, and revenue recognized from the Astellas Strategic Agreements and Astellas Collaboration Agreement.

Research and Development Expenses

Research and development expenses were $41.9 million for the three months ended September 30, 2024, compared to $37.5 million for the same period in 2023. The increase was primarily due to an increase in allogeneic clinical stage programs, driven mainly by an increase in overall enrollment of the Company’s allogeneic programs, and by an increase in preclinical stage programs and other unallocated expenses.

Research and development expenses were $130.4 million for the nine months ended September 30, 2024, compared to $114.7 million for the same period in 2023. The increase was primarily due to an increase in allogeneic clinical stage programs, driven mainly by an increase in overall enrollment of the Company’s allogeneic programs and the initiation of its third allogeneic clinical trial, P-CD19CD20-ALLO1, and by an increase in preclinical stage programs and other unallocated expenses.

General and Administrative Expenses

General and administrative expenses were $10.1 million for the three months ended September 30, 2024, and $32.1 million for the nine months ended September 30, 2024, compared to $8.1 million and $28.6 million for the same periods in 2023, respectively. The increases were primarily due to increased legal and professional fees as a result of higher patent-related and other consulting costs, and higher personnel expenses.

Net Income (Loss)

Net income was $20.2 million for the three months ended September 30, 2024, and net loss was $35.4 million for the nine months ended September 30, 2024, compared to net loss of $31.8 million and $98.1 million for the three and nine months ended September 30, 2023, respectively.

Cash Position

As of September 30, 2024, the Company’s cash, cash equivalents and short-term investments balance was $230.9 million. This includes $115 million in milestone and upfront payments generated in the first nine months of 2024, consisting of a $50 million upfront payment from the Astellas collaboration and $65 million from continued execution in the Company’s CAR-T partnership with Roche. The Company expects that its cash, cash equivalents and short-term investments together with these and other remaining near-term milestones and other payments from Roche will be sufficient to fund operations into early 2026. Potential additional anticipated progress and payments under the Roche Collaboration Agreement and/or potential additional business development could further extend the cash runway.

On November 7, 2024 Phio Pharmaceuticals Corp. (Nasdaq: PHIO) is a clinical-stage biotechnology company creating new pathways towards a cancer-free future by using its INTASYL siRNA gene silencing technology designed to make the body’s immune cells more effective in killing cancer cells, reported that it is presenting clinical data from its on-going Phase 1b clinical trial at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), which will be held in Houston, TX from November 8-10, 2024 (Press release, Phio Pharmaceuticals, NOV 7, 2024, View Source [SID1234647943]).

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Phio’s presentation will highlight the clinical results from enrolled patients in Cohorts 1 and 2 in the Phase 1b dose escalation clinical trial. This clinical trial is designed to evaluate the safety and tolerability of intratumoral injection of PH-762 in patients with cutaneous squamous carcinoma, Merkel cell carcinoma and melanoma.

Clinical Results To Date

Intratumoral (IT) injection of PH-762 has been well tolerated in all patients enrolled in the trial to date. There were no related adverse events, no serious adverse events, and no dose limiting toxicities or dose adjustments. Five (5) patients with cutaneous carcinomas have enrolled in Cohorts 1 and 2. Each enrolled patient received four (4) IT doses of PH-762. The patients were diagnosed with cutaneous squamous cell carcinoma (4 patients) and metastatic melanoma (1 patient).

At Day 36 (tumor excision), while each patient in the first cohort had stable disease, the following results were described for two patients enrolled in the second cohort:

· Complete response (100% tumor clearance) reported for 1 patient with cutaneous squamous cell carcinoma; and
· Partial response (90% tumor clearance) reported for 1 patient with cutaneous squamous cell carcinoma.

The Phase 1b trial is on-going. Anticipated completion of the enrollment phase of this trial is Q3 2025.

"We are encouraged by the documented clinical and histopathological results observed to date," said Mary Spellman MD, Phio’s acting Chief Medical Officer. "Corresponding safety and tolerability data supports continued assessment of intratumoral PH-762 in patients with cutaneous carcinomas."

Presentation Details are as follows:

Title: INTASYL PH-762: PD-1 Directed Intratumoral Immunotherapy for Cutaneous Carcinoma
Abstract Number: 696
Presenting Author: Mary Spellman, M.D.
Date: Saturday November 9, 2024
Location: Exhibit Halls A and B, George R. Brown Convention Center

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.

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)

•
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.
•
There were no cases of Grade >2 cytokine release syndrome (CRS) and no cases of immune effector cell-associated neurotoxicity (ICANS).
•
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

•
Nkarta had cash, cash equivalents, restricted cash, and investments in marketable securities of $405.3 million as of September 30, 2024.
•
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.
•
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.