On May 13, 2024 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported financial results for the first quarter ended March 31, 2024 (Press release, Leap Therapeutics, MAY 13, 2024, View Source [SID1234643147]).

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Leap Highlights:

· Completed $40 million private placement financing with participation from Gilead Sciences, Inc., a life sciences-focused investor, Samsara BioCapital, 683 Capital Partners, LP, Laurion Capital Management, and Rock Springs Capital
· Presented clinical data from Part A of the Phase 2 DeFianCe study evaluating DKN-01 in combination with standard of care bevacizumab and chemotherapy in second-line patients with advanced colorectal cancer (CRC), at the 2024 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium
· Expanded the ongoing randomized controlled Part B of the DeFianCe study from 130 patients to 180 patients to enhance the statistical power for patients with left-sided CRC; enrollment now expected to be completed in late Q3 or early Q4 2024
· Completed enrollment in the randomized controlled Part C of the Phase 2 DisTinGuish study evaluating DKN-01 in combination with tislelizumab and chemotherapy in patients with advanced gastroesophageal junction (GEJ) and gastric cancer; first randomized controlled data for DKN-01 expected in the second half of 2024 or early 2025

"We appreciate the strong support of Gilead and the new and existing institutional investors who participated in our recent $40 million financing that will enable the expansion and continued execution of the DKN-01 development program," said Douglas E. Onsi, President and Chief Executive Officer of Leap. "The financing provides cash runway into the second quarter of 2026, allowing the expansion of Part B of the DeFianCe CRC study to 180 patients, the full maturation of data in Part C of the DisTinGuish GEJ/gastric cancer study, and the manufacturing of Phase 3 clinical trial material. We are well positioned for continued success and look forward to achieving major clinical milestones in the year ahead."

Business Update:

· Completed a $40 million private placement. In April 2024, Leap entered into a securities purchase agreement with a select group of institutional investors to issue and sell an aggregate of 12,660,993 shares of its common stock ("Common Stock") at a price of $2.82 per share and pre-funded warrants to purchase 1,523,404 shares of Common Stock at a price of $2.819 per share of Common Stock issuable upon exercise of the pre-funded warrants, in a private placement. Gross proceeds from the private placement were approximately $40 million with participation from new and existing investors, including Gilead Sciences, Inc., a life sciences-focused investor, Samsara BioCapital, 683 Capital Partners, LP, Laurion Capital Management, and Rock Springs Capital. The net proceeds from this financing, combined with existing cash, cash equivalents and marketable securities, are expected to fund Leap’s operating and capital expenditures into the second quarter of 2026 and enable expansion of the DKN-01 DeFianCe clinical trial and development program.

DKN-01 Development Update

· Presented initial clinical data from Part A of the DeFianCe Study of DKN-01 plus bevacizumab and chemotherapy in colorectal cancer (CRC) patients. The Company presented initial data from Part A of the DeFianCe study (NCT05480306), a Phase 2 study evaluating DKN-01 in combination with standard of care (SOC) bevacizumab and chemotherapy in second-line (2L) patients with advanced microsatellite stable (MSS) CRC patients at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, held in San Francisco on January 18-20, 2024 and during the Company’s conference call on January 23, 2024.

· Key Findings (as of the December 6, 2023 data cutoff):

o Across all patients enrolled (n=33):

§ Overall response rate (ORR) among response-evaluable patients (n=27) was 30% and disease control rate (DCR) was 93%, including 8 partial responses (PR) and 17 patients with a best response of stable disease (SD)
§ Median progression-free survival (PFS) was 6.3 months
§ 9 patients remained on therapy and were beyond 8.5 months

o Enhanced activity in patients with left-sided tumors (n=25), a group that has more frequent activation of the Wnt pathway modulated by DKK1

§ 33% ORR and 100% DCR in response-evaluable population (7 PRs, 14 SDs)
§ Preliminary median PFS of 8.6 months (9 patients continuing therapy within subgroup)

o Compelling ORR, DCR and PFS in patients with rectal/rectosigmoid carcinomas (n=15), a population with increasing incidence among young people and shown to have the highest DKK1 levels:

§ 46% ORR and 100% DCR in response-evaluable population (6 PRs, 7 SDs)
§ Preliminary median PFS of 9.4 months (6 patients continuing therapy within subgroup)
§ Higher baseline plasma DKK1 levels correlated with improved responses

o DKN-01 plus bevacizumab and chemotherapy was well-tolerated, with a majority of DKN-01 related events being low grade (Grade 1/2)

· Part B of the DeFianCe Study of DKN-01 plus bevacizumab and chemotherapy in CRC patients is ongoing, with enrollment expanded to 180 patients and expected to be completed in late Q3/early Q4 2024. The Company expanded the randomized controlled Part B of the DeFianCe study from 130 to 180 patients and included PFS in the subpopulation of patients with left-sided CRC as an additional primary endpoint. The Company expects to complete enrollment in late Q3 or early Q4 2024 with data expected in mid-2025. As of May 8, 2024, 114 patients have enrolled in Part B.

· Completion of enrollment in the randomized controlled Part C of the DisTinGuish study evaluating DKN-01 in combination with tislelizumab, BeiGene’s anti-PD-1 antibody, and chemotherapy in patients with advanced gastroesophageal junction and gastric cancer. Part C of the DisTinGuish study (NCT0436380) is a Phase 2, randomized, open-label, multicenter study of DKN-01 in combination with tislelizumab and chemotherapy in first-line patients with advanced gastroesophageal adenocarcinoma. Part C enrolled 170 first-line, HER2-negative patients randomized 1:1 to evaluate DKN-01 in combination with tislelizumab and SOC chemotherapy, compared to tislelizumab and SOC chemotherapy alone. The primary objective is PFS in DKK1-high and in all patients. Secondary objectives of Part C include OS and ORR as measured by RECIST v1.1 in DKK1-high and in all patients. The Company expects to report initial data from Part C of the DisTinGuish study in the second half of 2024 or early 2025 when the PFS data are mature.

Selected First Quarter 2024 Financial Results

Net Loss was $13.8 million for the first quarter 2024, compared to $41.9 million for the same period in 2023. The decrease was primarily due to $29.6 million of in-process research and development ("IPR&D") expense associated with the Flame merger in January 2023.

Research and development expenses were $11.3 million for the first quarter 2024, compared to $38.9 million for the same period in 2023. The decrease of $27.6 million was primarily due to $29.6 million of IPR&D associated with the Flame merger. In addition, there was a decrease of $0.4 million in manufacturing costs related to clinical trial material manufacturing campaigns and a decrease of $0.1 million in consulting fees associated with R&D activities. These decreases were partially offset by an increase of $2.0 million in clinical trial costs and an increase of $0.5 million in payroll and other related expenses due to an increase in headcount of our R&D full-time employees.

General and administrative expenses were $3.5 million for the first quarter 2024, compared to $3.8 million for the same period in 2022. The decrease was due to a decrease of $0.3 million in professional fees associated with our business development activities.

Cash and cash equivalents totaled $54.9 million at March 31, 2024, exclusive of the $37.2 million net proceeds of the private placement completed in April 2024. Research and development incentive receivables, current portion, totaled $0.7 million at March 31, 2024.

On May 13, 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 for the first quarter of 2024 and provided an update on recent company developments (Press release, Inovio, MAY 13, 2024, View Source [SID1234643146]).

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"In the first quarter of 2024, we continued to deliver on our priorities for the year. Of utmost importance, we remain on track to submit our BLA in the second half of 2024 under the accelerated approval pathway for INO-3107 as a treatment for RRP and are working to initiate our confirmatory trial as soon as possible based on feedback from the FDA on the trial’s design. We are energized by the opportunity to potentially deliver the first FDA-approved therapy for this devastating disease and continue to work expeditiously to be prepared to serve RRP patients and the physicians caring for them. If approved, INO-3107 would also be the first DNA medicine on the market in the United States, representing a major milestone for our technology platform," said Dr. Jacqueline Shea, INOVIO’s President and Chief Executive Officer. "In parallel, we also made progress with our plans to evaluate INO-3112 in combination with the PD-1 inhibitor, LOQTORZI, in a Phase 3 trial, as we believe the combination could address a substantial unmet need in patients with locoregionally advanced, high-risk, HPV-16/18 positive OPSCC, a type of head and neck cancer commonly known as throat cancer. We believe that we are aligned with the FDA on our proposed Phase 3 trial design, and we now plan to discuss these plans with European regulators. We look forward to sharing our continued progress throughout the year."

Recent Business Highlights

INO-3107 – Recurrent Respiratory Papillomatosis (RRP)

INOVIO remains on target to submit its BLA seeking accelerated approval for INO-3107 in the second half of 2024. INOVIO is preparing trial sites for recruitment based on recent feedback from the FDA that they had no additional comments on INOVIO’s proposed design for the confirmatory trial. The trial is being strategically designed to focus on evaluating clinical benefit in reducing surgical intervention to control RRP disease for the majority of RRP patients. Repeat surgical interventions is the current standard of care for RRP. INOVIO’s market research to date with patients and healthcare professionals indicates that a reduction of even one surgery matters, because every surgery poses a significant risk of causing permanent damage to the vocal cords.
The proposed confirmatory trial will be randomized and placebo-controlled, involving approximately 100 patients with a history of ≥2 surgeries per year, with a treatment option for the placebo arm at trial end. This trial design is intended to target a broader spectrum of RRP disease than other candidates currently in development. If INO-3107 receives full approval from the FDA, INOVIO believes the design of the confirmatory trial could also support expansion into global markets based on feedback received to date from European regulators.
Immunological data highlighting INO-3107’s mechanism of action are expected to be submitted to peer-reviewed publications and key conferences in the second half of 2024.
INOVIO continues preparations to be ready to launch commercially in 2025, should INO-3107 be approved. Efforts are focused on building the infrastructure needed to deliver the product to patients as quickly and easily as possible, from distribution and supply efforts to payer and healthcare provider support. INOVIO believes that INO-3107, if approved, has the potential to be the preferred treatment of choice for all patients with RRP, as well as healthcare professionals and payers based on results from completed clinical trials and the competitive strengths of the DNA medicine platform:
Reduction in surgeries: 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 interventions during or after the dosing window. INOVIO’s Phase 1/2 trial was designed to show the potential of INO-3107 to reduce surgical intervention in the year following the first dose compared to the year prior. Relative to other Phase 1/2 clinical trials, INOVIO’s protocol required that all surgeries conducted during the dosing window (a 54-day period during which four doses were administered) be counted in the overall results. The protocol for INOVIO’s trial also did not include prescribed laryngoscopy and surgery at weeks 6 and 12 to maintain minimal residual disease during the treatment window. INOVIO believes that these contrasts with other clinical trial designs are important and could offer competitive advantages for INO-3107 should it be approved.
Mechanism of action: INO-3107 generated antigen specific T cells with lytic potential targeting both HPV-6 and HPV-11.
Immunology: Administration of INO-3107 induced active immune responses in the airway tissues of those patients who showed clinical response, including the production of cytokines and chemokines, known to be critical mediators of inflammatory responses, and increased activity of dendritic cells, macrophages and T cells. Additional analysis of T cell genes in airway tissues revealed an increase in CD4 and CD8 T cell gene signatures after treatment with INO-3107.
Benefits of DNA plasmids plus electroporation: INOVIO’s proprietary CELLECTRA devices are designed to optimally deliver DNA medicines within the body’s cells without requiring chemical adjuvants or lipid nanoparticles, and without the risk of pre-existing or anti-vector responses historically seen with viral vector platforms. In late-stage clinical trials involving approximately 5,600 doses administered to approximately 1,600 patients, intramuscular delivery has been well tolerated by patients and observed to be easy to use by healthcare providers. Based on historical data from other programs involving redosing, INOVIO believes it will be able to effectively re-dose INO-3107 if required to maintain or enhance immune responses.
INO-3112 – Oropharyngeal Squamous Cell Carcinoma (OPSCC)

The FDA provided feedback on the proposed Phase 3 trial design to evaluate the combination of INO-3112 and LOQTORZI as a potential treatment for patients with locoregionally advanced, high-risk, HPV-16/-18 positive throat cancer.
INOVIO will discuss the proposed trial design with European regulatory authorities, as INOVIO plans to conduct the trial in both Europe and North America.
The combination of INO-3112 with LOQTORZI has the potential to address a substantial unmet need in patients with HPV-16 and -18 related high-risk throat cancer. The proposed multi-center Phase 3 trial will investigate whether LOQTORZI can help boost the tumor-infiltrating abilities of the antigen-specific T cells generated by INO-3112.
INO-3112 is a DNA medicine candidate containing a DNA plasmid encoding HPV-16/-18 E6 and E7 antigens combined with another DNA plasmid encoding IL-12 as an immune activator.
LOQTORZI is an FDA-approved PD-1 inhibitor approved for the treatment of recurrent locally advanced/metastatic nasopharyngeal carcinoma.
General Corporate

Strengthened balance sheet with an offering of common stock and pre-funded warrants in April 2024; net proceeds from the offering, after deducting underwriting discounts and commissions and offering expenses, were approximately $33.2 million.
First Quarter 2024 Financial Results

Cash, Cash Equivalents and Short-term Investments: As of March 31, 2024, cash, cash equivalents and short-term investments were $105.6 million compared to $145.3 million as of December 31, 2023.

Research and Development (R&D) Expenses: R&D expenses for the three months ended March 31, 2024, were $20.9 million compared to $30.2 million for the same period in 2023. The decrease in R&D expenses was primarily the result of lower drug manufacturing costs related to INO-4800 and other COVID-19 studies that were discontinued, and lower employee and consultant compensation, including non-cash stock-based compensation, among other variances.

General and Administrative (G&A) Expenses: G&A expenses were $10.6 million for the three months ended March 31, 2024 compared to $13.9 million for the same period in 2023. The decrease in G&A expenses was primarily related to a decrease in employee compensation, including non-cash employee and consultant stock-based compensation, and a decrease in legal expenses, among other variances.

Total Operating Expenses: Total operating expenses were $31.5 million for the three months ended March 31, 2024, compared to $44.1 million for the same period in 2023.

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 were 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 three months ended March 31, 2024 was $30.5 million, or $1.31 per basic and diluted share, compared to net loss of $40.6 million, or $1.89 per basic and diluted share, for the three months ended March 31, 2023.

Shares Outstanding: As of March 31, 2024, INOVIO had 23.4 million common shares outstanding and 25.1 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 and convertible preferred stock.
INOVIO’s balance sheet and statement of operations are provided below. Additional information is included in INOVIO’s quarterly report on Form 10-Q for the quarter ended March 31, 2024, which can be accessed at: View Source

Cash Guidance
INOVIO estimates its cash runway, including the net proceeds of the April 2024 underwritten registered direct offering, to extend into the third quarter of 2025. This projection includes an operational net cash burn estimate of approximately $30 million for the second quarter of 2024. These cash runway projections do not include any further capital-raising activities that INOVIO may undertake.

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 May 13, 2024 Incyte Corporation (Nasdaq:INCY) (the "Company") reported that its Board of Directors approved a share repurchase authorization of $2.0 billion (Press release, Incyte, MAY 13, 2024, View Source [SID1234643145]). The Company has commenced a modified "Dutch Auction" tender offer to repurchase shares of its common stock for an aggregate purchase price of up to $1.672 billion (the "tender offer").

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"This tender offer reflects our confidence in the future outlook of our business, the strength of our commercial product portfolio and our clinical development pipeline and Incyte’s long-term value. We believe the current valuation of Incyte stock makes repurchases of our stock an attractive investment and an opportunity to enhance long-term shareholder value." said Hervé Hoppenot, Chief Executive Officer, Incyte. "Our strong balance sheet, cash flow and access to capital enable us to undertake this transaction while also preserving the flexibility to further add to the growth of our business through focused, strategic acquisitions."

In addition, on May 12, 2024, Incyte entered into a separate stock purchase agreement with Julian C. Baker (a member of Incyte’s Board of Directors), Felix J. Baker, and entities affiliated with Julian C. and Felix J. Baker, including funds advised by Baker Bros. Advisors LP (collectively, the "Baker Entities"), to repurchase up to $328.0 million of the Company’s common stock. This would enable the Baker Entities to maintain their current ownership level of approximately 16.4 percent of Incyte’s outstanding common stock. The Baker Entities purchase will be at the same price per share as is determined and paid in the tender offer.

Modified "Dutch Auction" Tender Offer

Incyte is offering to purchase up to $1.672 billion in value of its common stock at a price not greater than $60.00 per share nor less than $52.00 per share, net to the seller in cash, less any applicable withholding taxes and without interest, upon the terms and subject to the conditions set forth in the tender offer documents that are being distributed to stockholders. The Company reserves the right, in its sole discretion, to change the per share purchase price options and to increase or decrease the aggregate value of shares sought in the tender offer, subject to applicable law. In accordance with the rules of the Securities and Exchange Commission ("SEC"), Incyte may purchase in the offer up to an additional 2 percent of its outstanding shares without amending or extending the tender offer. On May 10, 2024, the Nasdaq closing price of the common stock was $53.06 per share. The tender offer will expire at 12:00 midnight, at the end of the day, New York City time, on Monday, June 10, 2024, unless extended.

A modified Dutch Auction tender offer allows stockholders to indicate how much stock they wish to tender and at what price within the range described above. Based on the number of shares tendered and the prices specified by the tendering stockholders, Incyte will determine the lowest price per share that will enable it to purchase $1.672 billion of common stock at such price, or a lower amount depending on the number of shares that are properly tendered and not properly withdrawn. All stock purchased in the tender offer will be purchased at the same price, even if a stockholder tendered at a lower price, so in some cases Incyte may purchase stock at a price above the price indicated by the stockholder tendering that stock. Incyte will not purchase stock below a stockholder’s indicated price. If the tender offer is fully subscribed, then $1.672 billion of common stock at the purchase price determined by Incyte will be purchased (subject to Incyte’s above-referenced ability to increase such numbers of shares), representing approximately 12.4 percent to 14.3 percent of outstanding common stock as of May 9, 2024, depending on the purchase price payable for those shares pursuant to the tender offer. Tenders of shares must be made prior to the expiration of the tender offer and may be withdrawn at any time prior to the expiration thereof.

If, at the final purchase price, shares representing more than $1.672 billion of common stock at the applicable purchase price (or such greater number of shares as Incyte may choose to purchase without amending or extending the offer) are properly tendered and not properly withdrawn, Incyte will purchase shares tendered at or below that price on a pro rata basis. The tender offer will not be conditioned on any minimum number of shares being tendered and will not be subject to a financing condition; however, the tender offer is subject to a number of other conditions described in the tender offer documents.

While Incyte’s Board of Directors has authorized the Company to make the tender offer, none of Incyte, its Board of Directors, the dealer manager or the information agent makes any recommendation to any stockholder as to whether to tender or refrain from tendering any shares or as to the price or prices at which stockholders may choose to tender their shares. Incyte has not authorized any person to make any such recommendation. Stockholders must decide whether to tender their shares and, if so, how many shares to tender and at what price or prices. In doing so, stockholders should carefully evaluate all of the information in the tender offer documents before making any decision with respect to the tender offer and should consult their own financial and tax advisors.

This press release is for informational purposes only and is not an offer to buy or the solicitation of an offer to sell any shares of common stock. The solicitation and offer to buy common stock will only be made pursuant to the offer to purchase and the other tender offer documents. A free copy of the tender offer documents that will be filed by Incyte with the SEC may be obtained when filed from the SEC’s website at www.sec.gov or from Incyte’s website at www.incyte.com, or by calling D.F. King & Co., Inc., the information agent for the tender offer, at (866) 864-4943 (toll free). Stockholders are urged to read these materials carefully prior to making any decision with respect to the offer. Stockholders who have questions may call the dealer manager for the tender offer, Goldman Sachs & Co. LLC at (212) 902-8226 or D.F. King & Co., Inc. at the number above.

Stock Purchase Agreement

The Company has entered into a stock purchase agreement with the Baker Entities. Under the stock purchase agreement, the Baker Entities have agreed not to tender or sell any shares in the tender offer and instead have agreed to sell to the Company, following completion of the offer, a pro rata number of shares based on the number of shares that the Company purchases in the offer such that the Baker Entities’ aggregate percentage ownership in the Company will be substantially equal to the Baker Entities’ current levels (the "Baker Entities Purchase"). The Baker Entities Purchase will be at the same price per share as is determined and paid in the offer and is expected to occur on the 11th business day following the expiration of the offer. The closing of the Baker Entities Purchase is subject to the completion of the offer. Assuming that the offer is fully subscribed, the aggregate purchase price for the shares purchased pursuant to the stock purchase agreement is anticipated to be approximately $328.0 million. The Baker Entities, in the aggregate, own 36,833,933 shares of common stock, representing in the aggregate beneficial ownership of approximately 16.4 percent of outstanding common stock as of May 9, 2024. If the tender offer is fully subscribed, the Company would repurchase a total of approximately $2.0 billion of its common stock through the tender offer and the stock purchase agreement (representing approximately 14.8 percent to 17.1 percent of the Company’s outstanding shares of common stock as of May 9, 2024, depending on the purchase price payable for those shares).

On May 13, 2024 IN8bio (Nasdaq: INAB), a clinical-stage biopharmaceutical company advancing innovative gamma-delta T cell therapies, reported in an oral session details about its robust and reproducible proprietary clinical-scale gamma-delta T cell manufacturing platform across different donor populations, at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 2024 Annual Meeting (Press release, In8bio, MAY 13, 2024, View Source [SID1234643144]).

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In an oral presentation titled: "Healthy Donor vs. Patient Manufactured Autologous DeltEx DRI Product; Immunophenotyping Gene Expression," IN8bio provided novel characterization data demonstrating the reproducibility and robust cellular properties of its clinical-scale manufactured investigational products. These data demonstrate that the manufacturing process results in investigational products with upregulated markers of potency, effector functions and trafficking capabilities, which IN8bio believes represents a significant advancement in the characterization of gamma-delta T cell-based therapies.

"The data presented provide additional insight on the complex gene-expression changes that occur throughout the manufacturing of our gamma-delta T cell products, which demonstrate a consistent profile at the end of manufacturing," said Dr. Kate Rochlin, Chief Operating Officer of IN8bio. "These new insights into the potency, effector functions, and trafficking changes that occur from initiation to the end of manufacturing in our gamma-delta T cells underscores the reproducibility and robustness of our manufacturing process. The data suggests that the characteristics of the final product are driven more by the manufacturing process than individual donor profiles. We seek to understand how key molecular characteristics allow the optimization of these unique therapies for potentially improved clinical outcomes."

The study evaluated T cell receptor repertoire and gene-expression changes from apheresis starting material through to final manufactured gamma-delta T cell products, from healthy donors and glioblastoma (GBM) patients enrolled in the INB-200 Phase 1 clinical trial (NCT04165941).

The gamma-delta T cell products demonstrated significant increases in markers of cellular activation and cytotoxicity, with enhanced expression of immune trafficking and stimulation markers, suggesting the potential for potent killing, tissue trafficking and immune cell recruitment in vivo.

The data also revealed highly similar gene expression profiles between gamma-delta T cell products manufactured from healthy volunteers and GBM patients, demonstrating the robustness and reproducibility of the manufacturing process across different donor populations.

On May 13, 2024 IMUNON, Inc. (NASDAQ: IMNN), a clinical-stage drug-development company focused on developing DNA-mediated immuno-oncology therapies and next-generation vaccines, reported financial results for the three months ended March 31, 2024 (Press release, IMUNON, MAY 13, 2024, View Source [SID1234643143]). The Company also provided an update on its clinical development programs with IMNN-001, a DNA-based interleukin-12 (IL-12) immunotherapy in Phase 2 clinical development for first-line treatment of locally advanced ovarian cancer, and on its PlaCCine modality, a proprietary mono- or multi-cistronic DNA plasmid and a synthetic DNA delivery technology for the expression of pathogen antigens for the development of next-generation vaccines.

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"Potential key value-creating milestones are upon us. We expect that this summer will be rewarding and busy as we look to improve the treatment paradigm in late-stage ovarian cancer and to offer an "mRNA-better" vaccine platform technology with excellent commercial promise," said Mr. Michael H. Tardugno, IMUNON’s Executive Chairman.

"We remain on track to report topline results from the OVATION 2 Study with IMNN-001 in advanced ovarian cancer in mid-2024. If interim data are confirmed, the observed progression-free survival (PFS) benefit would represent a clinically meaningful outcome. In September, we reported interim PFS and overall survival (OS) data suggesting an approximate 30% delay in disease progression or death in the treatment arm compared with the control arm, with the hazard ratio nearing the study objective. Preliminary OS data followed a similar trend, showing an approximate nine month improvement in the treatment arm over the control arm. Subgroup analyses suggest patients treated with a PARP inhibitor (PARPi) as maintenance therapy had longer PFS and OS if they were also treated with IMNN-001, compared with patients treated with neoadjuvant chemotherapy (NACT) only," he added.

"Our Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for our seasonal COVID-19 booster vaccine (IMNN-101) was accepted by the Agency. The Company has begun a Phase 1 proof-of-concept study in two investigational centers. Our goal is to confirm the safety and immunogenicity of this DNA-based vaccine as an annual booster with long-lasting protection. The first patients are expected to be enrolled during the current quarter, and based on the results, we intend to advance discussions with potential partners for further development. Our optimism is based, in part, on final data from non-human primate studies that showed excellent immunological response and viral clearance. In a recent mouse study, we demonstrated that a single dose of IMNN-101, without a booster dose, produced longer duration of IgG responses and higher T cell activation than an mRNA vaccine. We have also demonstrated continued drug stability at standard refrigerated temperature of 4°C for more than 12 months, representing a significant advantage over commercial mRNA-based vaccines."

Stacy Lindborg, PhD appointed President and Chief Executive Officer

With great pleasure, the Company announced the appointment of Stacy R. Lindborg, Ph.D. as President and Chief Executive Officer, effective May 13, 2024. Dr. Lindborg has served on IMUNON’s board of directors since 2021 and was most recently Co-Chief Executive Officer of BrainStorm Cell Therapeutics, where she remains a director.

"We are delighted that Dr. Lindborg has agreed to deepen her ties with IMUNON as President and CEO," said Mr. Tardugno. "We have benefited significantly from her counsel as a director, where she has played an integral role in establishing our strategic priorities. Stacy joins the Company at a particularly important time. We now look forward to benefiting from her expertise in a more meaningful way, especially as our near-term data readouts will require important decisions with respect to advancing various programs and assets."

Dr. Lindborg, a globally recognized biostatistician, has nearly 30 years of pharmaceutical and biotech industry experience with a particular focus on R&D, regulatory affairs, executive management and strategy development. She has worked with biologics, small molecules and cell therapies to address a range of diseases and disorders. She has extensive experience in early-stage development, having taken molecules from first-in-human studies into the clinic, through regulatory approval and commercial launch.

RECENT DEVELOPMENTS

IMNN-001 Immunotherapy

Reported Interim PFS and OS Data in OVATION 2 Study in Advanced Ovarian Cancer. In September 2023, the Company announced interim PFS and OS data with IMNN-001 in its OVATION 2 Study. This study is evaluating the dosing, safety, efficacy and biological activity of intraperitoneal IMNN-001 in combination with chemotherapy prior to tumor reduction surgery (known as: NACT) in patients newly diagnosed with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. NACT is designed to shrink the tumors as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT, patients undergo tumor debulking surgery, followed by three additional cycles of chemotherapy to treat any remaining tumor tissue.

The open-label study is directional and is designed to show an approximate 33% improvement in PFS when comparing the treatment arm with the control arm. Key secondary endpoints include OS, and the objective response rate. The final readout of this study is expected in mid-2024. A positive readout would inform the Phase 3 study design.

Interim data from the intent-to-treat population showed efficacy trends in PFS, demonstrating a delay in disease progression in the treatment arm of approximately three months compared with the control arm, with the hazard ratio nearing the study objective. Preliminary OS data followed a similar trend, showing an approximate nine-month improvement in the treatment arm over the control arm.
Non-prespecified subgroup analyses, commissioned as a result of the evolving standard of care for this population, suggest that patients treated with a PARPi as maintenance therapy had longer PFS and OS if they were also treated with IMNN-001, compared with patients treated with NACT only.
The median PFS in the PARPi + NACT group and the PARPi + NACT + IMNN-001 group was 15.7 months and 23.7 months, respectively.
The median OS in the PARPi + NACT group was 45.6 months and has not yet been reached in the PARPi + NACT + IMNN-001 group.
Began Treatment in a Phase 1/2 Clinical Trial Evaluating IMNN-001 in Combination with Bevacizumab (Avastin) in Advanced Ovarian Cancer. In October 2023, the first patient was enrolled in this trial at the University of Texas MD Anderson Cancer Center. This trial is expected to enroll 50 patients with Stage III/IV ovarian cancer. Patients undergoing frontline neoadjuvant therapy will be randomized 1:1 to receive standard chemotherapy plus bevacizumab, or standard chemotherapy plus bevacizumab and IMNN-001. The trial’s primary endpoint is detection of minimal residual disease (MRD) by second-look laparoscopy and the secondary endpoint is PFS. This trial will also include a wealth of translational endpoints aimed at understanding the clonal evolution and immunogenomic features of the MRD phase of ovarian cancer that is currently undetectable by imaging or tumor markers. In February 2024, the Company announced that Memorial Sloan Kettering Cancer Center joined MD Anderson Cancer Center in enrolling patients in this clinical trial.

PlaCCine: Developing the Prophylactic Vaccines of the Future

IND Application Cleared by the FDA to Begin Human Testing of IMNN-101. In April 2024, the Company announced receipt of FDA clearance to begin a Phase 1 proof-of-concept clinical trial with IMNN-101, a seasonal COVID-19 booster vaccine. Pending resolution of limited comments from the FDA, IMUNON expects to commence patient enrollment in the second quarter of 2024.

IMNN-101 utilizes the company’s PlaCCine platform, a proprietary mono- or multi-valent DNA plasmid that regulates the expression of key pathogen antigens and is delivered via a unique synthetic DNA delivery system. The primary objectives of the Phase 1 study are to evaluate safety, tolerability, neutralizing antibody response and the vaccine’s durability (duration of immunogenicity) in healthy adults. Secondary objectives include evaluating the ability of IMNN-101 to elicit binding antibodies and cellular responses and their associated durability. Based on reported preclinical data, durability of immune protection is expected to be superior to published mRNA vaccine data.

As currently planned, the Phase 1 study will enroll 24 subjects evaluating three escalating doses of IMNN-101 at two U.S. clinical trial sites. For this study, IMMN-101 has been designed to protect against the SARS-CoV-2 Omicron XBB1.5 variant, in accordance with the FDA’s Vaccines and Related Biological Products Advisory Committee’s June 2023 announcement of the framework for updated COVID-19 doses.

Preclinical Data for IMUNON’s PlaCCine DNA-Based Vaccine in SARS-CoV-2 Published in Peer-Reviewed Journal Vaccine. In February 2024, the Company announced that an article titled "Strong immunogenicity & protection in mice with PlaCCine: A COVID-19 DNA vaccine formulated with a functionalized polymer" was published in the peer-reviewed journal Vaccine, by Elsevier.

The article is available at View Source(24)00077-X.

The study described in the article used IMUNON’s proprietary formulation against the spike proteins from two SARS-CoV-2 variants, both alone and in combination. Data from the study show:

IMUNON’s proprietary formulation of functionalized polymer protected DNA from degradation and enhanced protein expression, while the combination with an adjuvant led to an increase in immunogenicity.
PlaCCine vaccines are stable for up to one year at 4°C and at least one month at 37°C.
Vaccination with PlaCCine resulted in the induction of spike-specific neutralizing antibodies and cytotoxic T cells.
In the in vivo challenge model, the vaccine-induced immune response was capable of suppressing viral replication.
Multiple inserts can be cloned into the PlaCCine backbone (a plug-and-play strategy), therefore allowing for an immune response with broader protection.
Corporate Developments

Received $1.3 Million in Non-Dilutive Funding from the Sale of New Jersey Net Operating Losses. In March 2024, the Company received $1.3 million in net cash proceeds from the sale of approximately $1.4 million of its unused New Jersey net operating losses (NOLs). The NOL sales cover the tax year 2022 and are administered through the New Jersey Economic Development Authority’s Technology Business Tax Certificate Transfer (NOL) program. This non-dilutive funding further strengthened the Company’s balance sheet.

FINANCIAL RESULTS FOR THE THREE MONTHS ENDED MARCH 31, 2024

IMUNON reported a net loss for the first quarter of 2024 of $4.9 million, or $0.52 per share, compared with a net loss of $5.6 million, or $0.68 per share, for the first quarter of 2023. Operating expenses were $5.0 million for the first quarter of 2024, a decrease of $0.7 million or 12% from $5.7 million for the first quarter of 2023.

Research and development (R&D) expenses were $3.3 million for the first quarter of 2024, an increase of $0.7 million from $2.6 million for the comparable period in 2023. Costs associated with the OVATION 2 Study were $0.3 million for both the first quarters of 2024 and 2023. Other clinical and regulatory costs were $1.1 million for the first quarter of 2024 compared with $0.3 million for the prior-year period. R&D costs associated with the development of IMNN-001 to support the OVATION 2 Study, as well as development of the PlaCCine DNA vaccine technology platform, were $1.6 million for the first quarter of 2024, compared with $1.4 million for the same period last year. CMC costs were $0.3 million for the first quarter of 2024, compared with $0.6 million for 2023 due to the development of in-house pilot manufacturing capabilities for DNA plasmids and nanoparticle delivery systems.

General and administrative expenses were $1.7 million for the first quarter of 2024, compared with $3.1 million for the comparable prior-year period. This decrease was primarily attributable to lower non-cash stock compensation expense ($0.3 million), lower legal costs ($0.5 million), lower employee-related costs ($0.2 million), lower consulting fees ($0.2 million) and lower insurance costs ($0.1 million).

Other non-operating income was $81,921 for the first quarter of 2024, compared with $93,085 for the comparable prior-year period. Investment income decreased $0.2 million due to lower balances of short-term investments in the current quarter. Interest expense decreased $0.2 million due to the repayment of the Company’s loan facility with Silicon Valley Bank in the second quarter of 2023.

Net cash used for operating activities was $5.9 million for the first quarter of 2024, compared with $4.0 million for the comparable prior-year period. This increase was primarily due to the final payment of CRO costs associated with the Phase III OPTIMA Study.

The Company ended the first quarter of 2024 with $9.8 million in cash, investments and accrued interest receivable. The Company believes it has sufficient capital resources to fund its operations to the end of 2024.

Conference Call and Webcast

The Company is hosting a conference call at 11:00 a.m. Eastern time today to provide a business update, discuss first quarter 2024 financial results and answer questions. To participate in the call, please dial 833-816-1132 (Toll-Free/North America) or 412-317-0711 (International/Toll) and ask for the IMUNON First Quarter 2024 Earnings Call. A live webcast of the call will be available here.

The call will be archived for replay until May 27, 2024. The replay can be accessed at 877-344-7529 (U.S. Toll-Free), 855-669-9658 (Canada Toll-Free) or 412-317-0088 (International Toll), using the replay access code 9343581. A webcast of the call will be available here for 90 days.