On June 28, 2024 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending conditional marketing authorization of odronextamab to treat adults with relapsed/refractory (R/R) follicular lymphoma (FL) or R/R diffuse large B-cell lymphoma (DLBCL), after two or more lines of systemic therapy (Press release, Regeneron, JUN 28, 2024, View Source [SID1234644595]). The European Commission is expected to announce a final decision in the coming months.

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FL and DLBCL are the two most common subtypes of B-cell non-Hodgkin lymphoma (B-NHL). While FL is a slow-growing subtype, it is an incurable disease, and most patients will relapse after initial treatment. DLBCL is an aggressive subtype, with up to 50% of high-risk patients experiencing progression after first-line treatment (e.g., relapsing or refractory to treatment). It is estimated that approximately 120,000 FL cases and 163,000 DLBCL cases are diagnosed annually worldwide. In Europe, it is estimated that approximately 15,000 FL cases and 31,000 DLBCL cases are diagnosed each year.

The positive CHMP opinion is supported by results from the Phase 1 ELM-1 and pivotal Phase 2 ELM-2 trials, which demonstrated robust, durable response rates and an acceptable safety profile of odronextamab in adults with R/R FL or R/R DLBCL. In a pooled safety population, the most common serious adverse reactions were cytokine release syndrome, pneumonia, COVID-19 and pyrexia.

The EMA previously granted odronextamab Orphan Designation for both FL and DLBCL. Odronextamab is currently under clinical development and has not been approved by any regulatory authority.

Regeneron continues to evaluate the use of odronextamab as a monotherapy and in combination across earlier lines of therapy in challenging-to-treat lymphomas. This includes the registrational ELM-1 and ELM-2 studies, the Phase 3 OLYMPIA development program, which is one of the largest clinical programs in lymphoma evaluating odronextamab in earlier lines of therapy and additional B-NHLs, as well as early-stage trials with chemotherapy-free combinations.

About the Odronextamab Clinical Trial Program
Odronextamab is an investigational CD20xCD3 bispecific antibody designed to bridge CD20 on cancer cells with CD3-expressing T cells to facilitate local T-cell activation and cancer-cell killing.

ELM-1 is an ongoing, open-label, multicenter Phase 1 trial to investigate the safety and tolerability of odronextamab in patients with CD20+ B-cell malignancies previously treated with CD20-directed antibody therapy, including a cohort of patients who had progressed after CAR-T therapy.

ELM-2 is an ongoing, open-label, multicenter Phase 2 trial investigating odronextamab across five independent disease-specific cohorts, including DLBCL, FL, mantle cell lymphoma, marginal zone lymphoma and other subtypes of B-NHL. The primary endpoint is objective response rate according to the Lugano Classification as assessed by independent review committee, and secondary endpoints include complete response, progression-free survival, overall survival and duration of response.

In addition to the Phase 3 OLYMPIA development program, Regeneron is investigating odronextamab in combination with a costimulatory bispecific antibody, REGN5837 (CD22xCD28), and Regeneron’s PD-1 inhibitor cemiplimab for R/R aggressive B-NHL through the ATHENA-1 and CLIO-1 studies, respectively. For more information, visit the Regeneron clinical trials website, or contact [email protected] or +1 844-734-6643.

On June 28, 2024 Pulse Biosciences, Inc. (Nasdaq: PLSE) (the "Company" or "Pulse Biosciences"), a company leveraging its novel and proprietary CellFX Nanosecond Pulsed Field Ablation (nsPFA) technology, reported the preliminary results of its rights offering, which expired at 5:00 p.m., Eastern Time, on June 26, 2024 (the "Expiration Date") (Press release, Pulse Biosciences, JUN 28, 2024, View Source [SID1234644616]).

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In accordance with the pricing structure described in the prospectus supplement relating to the rights offering, the final subscription price for the units offered (the "Units") is $10.00 per Unit. Each Unit consisted of one share of the Company’s common stock, par value $0.001 per share, and two warrants, each being a warrant to purchase one-half of one share of common stock. Each warrant will be exercisable for $11.00 per whole share, which equals 110% of the subscription price for the Units. Warrants are exercisable immediately and will expire on the fifth anniversary of the completion of the rights offering. Half of the warrants issued in the rights offering are redeemable by the Company if the Company’s stock trading price exceeds $16.50 for twenty consecutive trading days and the other half of the warrants issued in the rights offering are redeemable by the Company if its stock trading price exceeds $22.00 for twenty consecutive trading days.

Based on a preliminary tabulation by Broadridge Corporate Issuer Solutions, Inc. (the "Subscription Agent"), as of the Expiration Date, the Company received basic subscriptions and over-subscriptions in excess of $83 million, equal to approximately 138% of the $60 million limit in the rights offering, and subscriptions from over 800 accounts, including those of the Company’s Executive Chairman, Robert Duggan. Available Units will therefore be allocated proportionately among those rights holders who exercised their over-subscription right based on the number of Units each rights holder subscribed for under its basic subscription rights, in accordance with the procedures described in the prospectus relating to the rights offering, as amended, and the remaining oversubscription amounts will be returned by the Subscription Agent to the investors. The common stock and warrants comprising the Units will separate upon the closing of the rights offering and will be issued individually. The Company expects the Subscription Agent to distribute such shares and warrants, as well as the sale proceeds, as soon as practical upon the closing of the rights offering.

The Company expects to receive aggregate gross proceeds from the rights offering of $60 million, excluding additional proceeds of up to $66 million from the exercise of warrants issued in the rights offering (if any such exercises occur). The results of the rights offering are preliminary and subject to change pending finalization of subscription procedures by the Subscription Agent.

The rights offering was made pursuant to the Company’s registration statement on Form S-3, as modified by the post-effective amendment filed with the Securities and Exchange Commission ("SEC") on May 28, 2024, which was deemed effective by the SEC on May 31, 2024, including the prospectus contained therein, as further modified by the prospectus filed pursuant to Rule 424(b)(2) of the Securities Act of 1933, which contains the detailed terms of the rights offering and was filed with the SEC on June 4, 2024. Copies of the foregoing documents may be obtained at the SEC’s website at www.SEC.gov. Subscription rights that were not exercised by 5:00 p.m., Eastern Time, on June 26, 2024, have expired.

On June 28, 2024 Agenus Inc. ("Agenus") (Nasdaq: AGEN), a leader in developing novel immunological agents to treat various cancers, reported results from an investigator-sponsored trial (IST) of botensilimab and balstilimab (BOT/BAL) in the neoadjuvant setting for colon cancer (Press release, Agenus, JUN 28, 2024, View Source [SID1234644598]). Data were presented at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Gastrointestinal Cancers Congress in Munich, Germany.

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Dr. Pashtoon Kasi, the originator of this groundbreaking study, stated, "The rapid and complete resolution of aggressive MSS colorectal cancer tumors observed in this study is unprecedented in the field. The exceptional activity of the BOT/BAL combination therapy in the neoadjuvant setting offers new hope for patients facing this challenging cancer subtype. Furthermore, the pattern of response and the lack of clinical recurrence speaks to the curative potential of one’s own body to fight cancer."

Study Highlights:

Enrollment: 20 patients were evaluable at the data cutoff with available pathology results, 17 microsatellite stable (MSS) and 3 high microsatellite instability (MSI-H).
Treatment Regimens: Both cohorts received one dose of botensilimab with balstilimab. The NEST-1 cohort received one additional dose of balstilimab two weeks later, whereas the NEST-2 cohort received up to 3 additional doses of balstilimab.
Clinical Findings:

Pathologic Response: In the NEST-2 cohort, 78% (7/9) of MSS patients achieved pathologic responses of at least 50% tumor regression, with 56% (5/9) reaching complete pathologic responses.
Surgical Outcomes and Safety: No surgeries were delayed due to adverse events, and no patients had unresolved immune related adverse events. Side effects were manageable, and no new safety concerns emerged.

Pathologic Response

(>50% Regression)

Complete Pathologic Response

(100% Regression)

NEST-1 (N=10)

MSS (N=8)

5 (63%)

1 (13%)

MSI-H (N=2)

2 (100%)

1 (50%)

NEST-2 (N=10)

MSS (N=9)

7 (78%)

5 (56%)

MSI-H (N=1)

1 (100%)

1 (100%)

Overall

MSS (N=17)

12 (71 %)

6 (35%)

MSI-H (N=3)

3 (100%)

2 (67%)

"The significant tumor reductions observed with the early use of BOT/BAL therapy before surgery underscore its paradigm-changing potential in neoadjuvant colon cancer, potentially minimizing the rate of disease recurrence and the need for invasive procedures and chemotherapy in the future," said Dr. Steven O’Day Chief Medical Officer at Agenus. "The responses in MSS patients were particularly profound, and extending the treatment duration in the NEST-2 cohort further amplified these effects. We are focused on expanding BOT/BAL’s application in the neoadjuvant setting to improve treatment for individuals living with cancer."

The presentation is available on the Agenus website at View Source

About Botensilimab

Botensilimab is a human Fc enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to "cold" tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.

Approximately 900 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.

About Colorectal Cancer

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States, comprising an estimated 8.3% of cancer-related deaths annually. Although overall mortality from CRC has declined, survival remains poor for advanced disease, and the burden is shifting to a younger population. Alarmingly, from 1995 to 2019, the number of patients under the age of 55 who were diagnosed with CRC in the United States nearly doubled.

On June 28, 2024 TME Pharma N.V. (Euronext Growth Paris: ALTME), a clinical-stage biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported results of the second exercise of Warrants Z and an update on the outstanding number of ordinary shares and Warrants Z as of the settlement date taking place today (Press release, TME Pharma, JUN 28, 2024, View Source [SID1234644618]). The exercise of 513,472 Warrants Z has resulted in the issuance of 641,840 new shares for gross proceeds of €128,368, an amount similar to that generated in the first exercise period.

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In the second Warrant Z exercise period, from May 27 to June 21, 2024, holders were entitled for every 4 Warrants Z held to subscribe for 5 new shares at €0.20 per share. Following this exercise, 2,812,632 outstanding Warrants Z remain with the potential to raise an additional €703,158 if exercised in full before the end of the final exercise period on June 20, 2025.

The following numbers of TME Pharma securities are thus issued and outstanding:

ALTME ordinary shares (ISIN: NL0015000YE1): 42,183,371
Warrants Z (ISIN: NL0015001SR3): 2,812,632
The third Warrant Z exercise period will run from August 26 to September 20, 2024, with settlement on September 27, 2024. Warrants Z may be exercised through June 20, 2025, with one period of exercise per quarter (six periods of exercise in total; see "Warrant Terms and Conditions" on the TME Rights Issue page for more details). Warrants Z that have not been exercised by the end of the last exercise period will become null and void.

Additional Information

The characteristics, terms and conditions and dilution resulting from the transaction are summarized in the press releases published on November 24, 2023, November 28, 2023, and February 23, 2024, and in the dedicated Rights Issue page on the TME Pharma website.

Dilution

The table below summarizes the dilution from the new ordinary shares issued today, and the maximum additional dilutive potential for an investor who did NOT participate in the transaction should all potential Warrants Z be exercised. Shareholders who participated fully in the transaction will not be diluted by this transaction.

Description

Shares to be issued

Total shares outstanding

Dilution (cumulative)

Shareholder starting with 1% on June 27, 2024, would then hold

Outstanding shares on June 27, 2024

–

41,541,531

–

1%

Shares Issued on June 28, 2024, from exercise of 513,472 Warrants Z

641,840

42,183,371

1.52%

0.98%

Exercise of outstanding Warrant Z (latest on June 20, 2025)

3,515,790

45,699,161

9.10%

0.91%

On June 28, 2024 BridGene Biosciences, Inc., a leader in developing covalent small molecule drugs for traditional "hard-to-drug" targets, reported that the first patient has been dosed in its Phase 1 clinical trial of BGC515, a novel TEAD inhibitor discovered through BridGene’s cutting-edge chemoproteomic platform, IMTAC (Press release, Bridgene Biosciences, JUN 28, 2024, View Source [SID1234644599]). This milestone highlights the potential of BridGene’s innovative chemoproteomics approach.

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The Phase 1 study will enroll subjects in both the US and China (NCT06452160) to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGC515 as a single agent in patients with advanced solid tumors, including malignant mesothelioma, epithelioid hemangioendothelioma, and other solid tumors with hippo pathway dysregulation. Dr. Timothy Yap, Ph.D., FRCP, Professor in the Department of Investigational Cancer Therapeutics (Phase I Program) and Head of Clinical Development, Therapeutics Discovery Division at the University of Texas MD Anderson Cancer Center, is the principal investigator at the initial US site, where the first patient has been enrolled.

"We are delighted to begin the clinical evaluation of BGC515 with the dosing of our first patient, and we look forward to the evaluation of the initial safety and efficacy of this exciting compound," said Jeremy Barton, M.D., Chief Medical Officer of BridGene Biosciences.

"The initiation and dosing of our first drug in clinical development from our chemoproteomic platform marks a major inflection point for BridGene," stated Ping Cao, Ph.D., Co-Founder and CEO of BridGene Biosciences. "This achievement underscores our commitment to addressing unmet medical needs through innovative therapeutic solutions. BGC515 represents a breakthrough in targeting the TEAD proteins, a critical component in the Hippo signaling pathway. We are proud of the progress we have made in a short time, developing a pipeline that includes previously undruggable targets for prominent oncology and immunology diseases."

BridGene Biosciences is advancing multiple novel drug discovery programs toward the clinic and has over a dozen similar opportunities emerging in early discovery.

About the Hippo Pathway and BGC515
The Hippo pathway is a key pathway used by cells to control expression of a group of genes by regulating activity of transcription factors YAP and TAZ. YAP and TAZ function in a complex with partner proteins, the TEADs, which are the targets of BGC515. A variety of human cancers depend on activation of YAP and TAZ, which can occur by various mechanisms.

BGC515 is an internally-developed, orally-administered, covalent TEAD inhibitor.