On March 6, 2024 Laminar Pharmaceuticals S.A., a clinical-stage biotechnological company developing novel therapies to treat diverse pathologies with unmet clinical needs, reported that the Independent Data Monitoring Committee (IDMC) after evaluating the interim clinical results of the CLINGLIO clinical trial, has recommended that the trial should "continue without modifications" (Press release, Laminar Pharma, MAR 6, 2024, View Source [SID1234640861]). The CLINGLIO study is a multinational, phase 2b/3, randomized, double-blind clinical trial evaluating LAM561 in combination with standard-of-care (SoC; combined tumour resection and chemoradiotherapy) for newly diagnosed glioblastoma (GBM) patients. The CLINGLIO trial, funded by a European Commission Grant (H2020) is being carried out in 21 hospitals in Spain, Italy, France, and UK. The investigational study drug, LAM561 (idroxioleic acid, sodium; 2-OHOA) is a synthetic fatty acid with a novel therapeutic approach, administrated orally to treat this devastating type of cancer.

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As part of the pre-specified plan, the experts from the IDMC committee at their meeting on February 23 recommended, based upon their evaluation of the unblinded medical and clinical statistical data from 103 patients, that the CLINGLIO trial should continue without modification. This interim analysis was conducted following the committee’s assessment of the efficacy – survival without progression (tumor growth or clinical deterioration) – of LAM561 after 45 progression events have occurred. This recommendation was eagerly awaited by Laminar as it ensures that the trial remains on track to have its first open readout at 66 progressions, expected in the Summer of 2024. Moreover, this interim recommendation by the IDMC confirms that with the current level of evidence, futility (lack of clinical benefit of the drug) has not been identified and continuance of the study is recommended.

"The positive IDMC interim review of LAM561 efficacy in newly diagnosed GBM represents a leap forward for our most advanced development. This is the first time that the efficacy of LAM561 has been assessed against placebo, a huge milestone in the project, and this recommendation was the best possible outcome at this stage" said Dr Pablo Escribá, Chief Executive Officer of Laminar Pharmaceuticals. "With the IDMC’s recommendation, we will continue to advance the CLINGLIO study to confirm the potential of LAM561 to improve the prognosis and quality of life in first-line glioblastoma patients treated with standard-of-care."

From Laminar’s point of view, this positive and expected recommendation follows the encouraging results from previous IDMC meeting, focused on safety, held in September 2023, in which no concerns were raised based on evaluation of the available safety data. Subsequent ongoing follow-up and monitoring of medical and pharmacovigilance data have not raised any further safety concerns to the medical team and study monitor nor the trial’s Ethics Board. Oral LAM561 has been well tolerated and indicates a safety profile consistent with prior clinical trials.

"A leap forward, and also the beginning of the last step to potentially reach clinical practice, as the next planned interim analysis will provide the unblinded clinical benefit/risk ratio data needed for the request for Conditional Market Authorization." – added Dr Adrian G. McNicholl, Laminar’s Chief of Clinical Operations. "However, even though we are hopeful with the advancement of the LAM561 clinical program, we must be careful not to raise patient’s expectations, as this is an investigational medicinal product, and we need to wait until the outcome of the next interim analysis has been re-evaluated by the IDMC and has been assessed by the regulatory agencies with whom we are already in direct contact".

As a designated orphan medicinal product in the EU, the study protocol, scientific validity, methodology, analyses and endpoints have been discussed in detail with the EMA during successive requests for Protocol Assistance. The CLINGLIO trial is considered pivotal in that results showing significant clinical benefit could be sufficient for a request for conditional marketing authorization in the EU late this year; and potential full marketing authorization in 2025, for which enabling pre-submission interactions with the EMA have been initiated.

On March 6, 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 dosing of the first patient with KO-2806, the Company’s next-generation farnesyl transferase inhibitor (FTI), in combination with the tyrosine kinase inhibitor (TKI) cabozantinib in the clear cell renal cell carcinoma (ccRCC) cohort of the Phase 1 portion of the FIT-001 trial (Press release, Kura Oncology, MAR 6, 2024, View Source [SID1234640860]).

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"Dosing of the first patient in combination in our Phase 1 trial of KO-2806 marks a significant milestone for our next-generation FTI program," said Stephen Dale, M.D., Chief Medical Officer of Kura Oncology. "This innovative, first-in-human trial builds upon our leadership position in the development of FTIs as well as a growing body of preclinical data demonstrating that combining KO-2806 with certain tyrosine kinase inhibitors, including cabozantinib, can drive tumor regressions and enhance both duration and depth of antitumor response in preclinical models of ccRCC. With this achievement, we are now one step closer to realizing our vision for broad application of KO-2806 as an ideal combination partner to drive enhanced antitumor activity and address mechanisms of innate and adaptive resistance to targeted therapies."

FIT-001 is a first-in-human, multicenter, open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of KO-2806 when administered as monotherapy and in combination with targeted therapies. Concurrent with the monotherapy dose escalation, Kura is evaluating KO-2806 in dose-escalation combination cohorts with other targeted therapies, beginning with cabozantinib in ccRCC. The Company expects to begin dosing in combination with adagrasib in KRASG12C-mutant non-small cell lung cancer (NSCLC) next quarter. For more information regarding FIT-001, please visit www.clinicaltrials.gov (identifier: NCT06026410).

About KO-2806

KO-2806 is a next-generation inhibitor of farnesyl transferase designed to improve upon the potency, pharmacokinetic and physicochemical properties of earlier FTI drug candidates. At the 2023 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), Kura presented promising preclinical data supporting the rationale for combining KO-2806 with distinct classes of targeted therapies, including tyrosine kinase inhibitors, KRASG12C inhibitors and KRASG12D inhibitors. Additional information about clinical trials for KO-2806 can be found at View Source

On March 6, 2024 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that the Company’s senior management team will participate in the Leerink Partners Global Biopharma Conference on Tuesday, March 12, 2024 and present at the Barclays 26th Annual Global Healthcare Conference in a fireside chat on Wednesday, March 13, 2024 at 9:00 a.m. ET in Miami Beach, FL (Press release, Karyopharm, MAR 6, 2024, View Source [SID1234640859]).

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A live webcast of the fireside chat at the Barclays conference can be accessed under "Events & Presentations" in the Investor section of the Company’s website, View Source, and will be available for replay following the event.

On March 6, 2024 INOVIO (NASDAQ:INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, reported its financial results and operational highlights for the fourth quarter and full year ended December 31, 2023 (Press release, Inovio, MAR 6, 2024, View Source [SID1234640858]).

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INOVIO’s President and Chief Executive Officer, Dr. Jacqueline Shea, said, "The past year has been transformative as we’ve reshaped INOVIO into a company that is focused on commercializing its first product candidate and bringing the benefits of DNA medicine to patients. We’ve done so by focusing on the strengths of our platform and our strategic objectives: advancing candidates with scientific promise, achievable pathways to market, and strong commercial potential, and maintaining an ongoing commitment to financial discipline and operational excellence."

Dr. Shea continued, "In the past year we have taken our lead candidate, INO-3107 for RRP, from positive Phase 1/2 trial results to Breakthrough Therapy designation and an established path to BLA submission under the FDA’s accelerated approval program. We’ve also announced a new clinical collaboration and supply agreement with Coherus BioSciences to advance our development of INO-3112 in combination with LOQTORZI (toripalimab-tpzi) for throat cancer, shared encouraging results for INO-4201 as an Ebola vaccine booster, continued to advance other clinical-stage candidates, and progressed important preclinical research opportunities. The year ahead will provide a critical opportunity to carry this positive momentum forward across our pipeline, particularly for INO-3107 as we prepare for BLA submission and the initiation of a confirmatory trial in the second half of 2024 and accelerate commercialization efforts for a potential 2025 launch."

Operational Highlights

INO-3107 – Recurrent Respiratory Papillomatosis (RRP)
INOVIO made significant progress with INO-3107 as a potential treatment for RRP. Key milestones included positive clinical results, regulatory progress, and the acceleration of commercialization efforts to be prepared to launch in 2025.

INOVIO announced and published positive data from a completed Phase 1/2 clinical trial evaluating INO-3107 for the treatment of HPV-6 and HPV-11-related RRP in adults.
In the trial, 81.3% (26/32) of patients had a decrease in surgical interventions in the year after INO-3107 administration compared to the year prior to treatment, including 28.1% (9/32) that required no surgical intervention during or after the dosing window.
Patients in the trial had a median range of 4 surgeries (2-8) in the year prior to dosing. After dosing, there was a median decrease of 3 surgical interventions (95% confidence interval -3, -2).
Prior to the outset of the trial (Day 0), patients had RRP tissue surgically removed, but any surgery performed after Day 0 during the dosing window was counted against the efficacy endpoint.
Treatment with INO-3107 generated a strong immune response in the trial, inducing activated CD4 T cells and activated CD8 T cells with lytic potential. T-cell responses were also observed at Week 52, indicating a persistent cellular memory response.
INO-3107 was well tolerated by participants in the trial, resulting in mostly low-grade (Grade 1) treatment-emergent adverse effects such as injection site pain and fatigue.
This data was presented at the 103rd Annual Meeting of the American Broncho-Esophageal Association at the 2023 Combined Otolaryngology Spring Meetings in May 2023, and published in The Laryngoscope in June 2023.
INOVIO announced its plans to submit its BLA for INO-3107 in the second half of 2024.
Breakthrough Therapy designation was granted by the FDA in September 2023.
FDA advised in October 2023 that INOVIO’s completed Phase 1/2 trial could be used to submit its BLA under the accelerated approval program.
European Commission granted Orphan Drug designation in May 2023, building upon the U.S. Orphan Drug designation granted by the FDA in 2020 and the CE marking issued by the European Union in 2018 to INOVIO’s delivery device, CELLECTRA.
INOVIO has accelerated its commercialization strategy to support a product launch in 2025 if regulatory approval is obtained on the anticipated timeline.
Plans underway include strategies for product distribution and logistics, payor engagement and reimbursement, specialty pharmacy identification, customer service programs, field force design, and other sales and marketing activities.
Continuing to deepen its market understanding of RRP as a disease, including patient and healthcare provider needs.
INO-3112 – Oropharyngeal Squamous Cell Carcinoma (OPSCC)
In January 2024, INOVIO announced a clinical collaboration and supply agreement with Coherus BioSciences, Inc. to evaluate the combination of INO-3112 and LOQTORZI as a potential treatment for patients with locoregionally advanced, high-risk, HPV-16/18 positive oropharyngeal squamous cell carcinoma (OPSCC), a type of head and neck cancer commonly known as throat cancer.

Under the terms of the agreement, Coherus will provide LOQTORZI for a planned clinical trial at no cost to INOVIO.
LOQTORZI is a PD-1 inhibitor recently approved by the FDA for the treatment of recurrent locally advanced/metastatic nasopharyngeal carcinoma.
INO-3112 is a DNA medicine candidate targeting HPV-16/18 combined with a DNA plasmid for IL-12 as an immune activator.
INOVIO has submitted the proposed design of a Phase 3 trial to the FDA with the intent to evaluate the clinical benefit of INO-3112 in combination with a PD-1 inhibitor. Feedback on the clinical development plan is expected in the second quarter of 2024. If cleared to proceed by the FDA, the trial will investigate if LOQTORZI can help boost the tumor-infiltrating abilities of the antigen-specific T cells generated by INO-3112.
INO-4201 – Ebola Booster for rVSV-ZEBOV (Ervebo)
INOVIO announced results from a Phase 1b clinical trial in healthy adult participants who previously received a single injection of Ervebo. In the trial, INO-4201 was well tolerated and boosted humoral responses in 100% (36 of 36) of treated participants. INOVIO believes these data indicate that DNA medicines could be an important part of global medical countermeasures against infectious diseases, either as primary vaccines or boosters to existing vaccines. The FDA has provided feedback on a potential development pathway to licensure and INOVIO expects to finalize these plans and discuss with collaborators and potential partners in the first half of 2024.

INO-5401 – Glioblastoma (GBM)
INOVIO is finalizing its clinical study report from a Phase 1/2 trial of INO-5401 and INO-9012 in combination with Regeneron’s PD-1 inhibitor Libtayo (cemiplimab) in newly diagnosed GBM patients. The data from this trial showed encouraging median overall survival results from 52 patients and evidence of antigen-specific T cells that may infiltrate GBM tumors. Through 2023, patients involved in the trial continued to receive drug. In the first half of 2024, INOVIO expects to finalize next steps for further development of INO-5401 in conjunction with Regeneron and investigators.

Fourth Quarter and Full Year 2023 Financial Results

Cash, Cash Equivalents and Short-term Investments: As of December 31, 2023, cash, cash equivalents and short-term investments were $145.3 million compared to $253.0 million as of December 31, 2022.

Revenues: Total revenue was $103,000 and $832,000 for the quarter and year ended December 31, 2023, respectively, compared to $125,000 and $10.3 million for the same periods in 2022, respectively. The revenue generated in 2022 was associated with a Procurement Contract with the U.S. Department of Defense for INOVIO’s devices and accessories to be used for delivery of its COVID-19 vaccine candidate, INO-4800, which the company has discontinued.

Research and Development (R&D) Expenses: R&D expenses for the quarter and year ended December 31, 2023 were $17.3 million and $86.7 million, respectively, compared to $42.1 million and $187.7 million, respectively, for the same periods in 2022. The decrease in R&D expenses was primarily the result of lower drug manufacturing, clinical trial expenses, outside services and expensed inventory related to INO-4800 and other COVID-19 studies and lower employee and consultant compensation, including stock-based compensation, among other variances.

General and Administrative (G&A) Expenses: G&A expenses were $10.2 million and $47.6 million, respectively, for the quarter and year ended December 31, 2023, versus $14.0 million and $90.2 million, respectively, for the same periods in 2022. The decrease in G&A expenses was primarily due to significant costs incurred in the second quarter of 2022 related to the settlement of class action litigation and related legal expenses, severance expenses incurred in 2022 and lower employee and consultant compensation in 2023, including stock-based compensation, among other variances.

Total Operating Expenses: Total operating expenses were $27.5 million and $144.8 million for the quarter and year ended December 31, 2023, respectively, compared to $56.1 million and $277.8 million for the same period in 2022. During the third quarter of 2023, the company recognized a non-cash goodwill impairment charge of $10.5 million.

Reverse Stock Split: INOVIO effected a reverse stock split of its outstanding shares of common stock on January 24, 2024, as a result of which every twelve shares of its common stock issued and outstanding was combined into one share of common stock. Any fractional post-split shares as a result of the reverse split were eliminated and redeemed in cash. Outstanding share amounts and per share amounts included in this press release have been restated to reflect the reverse stock split on a retroactive basis for all periods presented.

Net Loss: INOVIO’s net loss for the quarter and year ended December 31, 2023 was $25.0 million, or $1.10 per basic and diluted share, and $135.1 million, or $6.09 per basic and diluted share, respectively, compared to net loss of $54.5 million, or $2.61 per basic and diluted share, and $279.8 million, or $14.07 per basic and diluted share, for the quarter and year-ended December 31, 2022, respectively.

Shares Outstanding: As of December 31, 2023, INOVIO had 22.8 million common shares outstanding and 24.5 million common shares outstanding on a fully diluted basis, after giving effect to the exercise, vesting, and conversion, as applicable, of its outstanding options, restricted stock units, convertible preferred stock, and convertible debt.
INOVIO’s balance sheet and statement of operations are provided below. Additional information is included in INOVIO’s annual report on Form 10-K for the year ended December 31, 2023, which can be accessed at: View Source

Cash Guidance
INOVIO estimates its cash runway to extend into the second quarter of 2025. This projection includes an operational net cash burn estimate of approximately $26 million for the first quarter of 2024. This amount excludes the repayment of $17 million in remaining principal and accrued interest on convertible senior notes that matured on March 1, 2024. Including the repayment, the total net cash burn for the first quarter of 2024 is expected to be approximately $43 million. These cash runway projections do not include any funds that may be raised through the company’s existing at-the-market program or other capital-raising activities.

Conference Call / Webcast Information
INOVIO’s management will host a live conference call and webcast with slides at 4:30 p.m. ET today to discuss INOVIO’s financial results and provide a general business update. The live webcast and replay may be accessed by visiting INOVIO’s website at View Source

On March 6, 2024 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported the first patient was dosed in its Phase 1/2 multicenter trial (NCT06088654), investigating the safety and tolerability of IPH6501 in patients with Relapsed and/or Refractory CD20-expressing B-cell Non-Hodgkin’s Lymphoma (NHL) (Press release, Innate Pharma, MAR 6, 2024, View Source [SID1234640857]).

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IPH6501 is Innate’s first-in-class CD20-targeting tetraspecific ANKET (Antibody-based NK cell Engager Therapeutics) that co-engages CD20 as a target antigen on malignant B cells and three receptors on NK cells: two activating receptors (NKp46 and CD16) and the interleukin-2 receptor (but not its alpha subunit), with a human IL‑2 variant, hence providing proliferation and activation signals targeted to NK cells and promoting their cytotoxic activity against CD20 expressing malignant cells. The study is planned to enroll up to 184 patients.

"We are pleased to announce the dosing of a first patient in this Phase 1/2 study evaluating IPH6501, our proprietary ANKET asset and the first tetraspecific NK Cell Engager to enter the clinic." commented Dr Sonia Quaratino, Chief Medical Officer at Innate Pharma. "With the addition of the IL-2 variant, our second generation ANKET molecules can deliver proliferation signals to NK cells, and thus enhance their effector functions against cancer cells. Thanks to this novel format, IPH6501 represents a promising alternative strategy to T cell therapies for patients with B-cell non-Hodgkin’s lymphomas."

"The discovery and implementation of novel chemotherapies, T-cell based immunotherapies and targeted therapies have improved outcomes for patients with B-cell non-Hodgkin’s lymphomas compared with traditional chemotherapy." added Dr Lorenzo Falchi, Lymphoma Specialist at the Memorial Sloan Kettering Cancer Center, New-York, and principal investigator of the study. "However, many patients fail to achieve a response to or develop disease relapse after treatment. In this context, IPH6501 represents an innovative option for the treatment of patients with R/R B-cell non-Hodgkin’s lymphomas and has the potential to fulfil a large unmet need."

More information about the trial can be found on clinicaltrials.gov.

About B-Cell Non-Hodgkin’s Lymphoma
B-cell lymphomas are clonal tumors of mature and immature B cells that constitute the majority (80-85%) of NHLs. NHLs are a heterogeneous group of lymphoproliferative malignancies. NHL usually originates in the lymphoid tissues and can spread to other organs. NHL is the most common hematological malignancy worldwide, accounting for nearly 3% of cancer diagnoses and deaths.
According to the latest World Health Organization (WHO) classification, the most common B-NHL in Western countries is Diffuse large B cell lymphoma (DLBCL), accounting for around 31% of adult cases. Other common aggressive B-cell subtypes include Mantle Cell Lymphoma (MCL) (6% of cases) and Burkitt lymphoma (BL) (2% of cases). Among indolent B-cell NHL, Follicular Lymphoma (FL) accounts for 22% of cases in the Western world, followed by marginal zone lymphoma (MZL) (8% of cases).

About IPH6501
IPH6501 is the first Antibody-based NK cell Engager Therapeutic to co-engage activating receptors on NK cells (NKp46 and CD16), IL-2R (but not subunit) through a variant of human IL-2, and a tumor antigen (CD20) via a single molecule, hence providing proliferation and activation signals targeted to NK cells and promoting their cytotoxic activity against CD20 expressing malignant cells. IPH6501 has shown better anti-tumor efficacy than approved benchmark antibodies in preclinical tumor models (Demaria, EHA (Free EHA Whitepaper) 2023).

About ANKET
ANKET (Antibody-based NK cell Engager Therapeutics) is Innate’s proprietary platform for developing next-generation, multispecific natural killer (NK) cell engagers to treat certain types of cancer. This fit-for-purpose technology is creating an entirely new class of molecules to induce synthetic immunity against cancer.