On April 11, 2024 Boundless Bio (Nasdaq: BOLD), a clinical-stage oncology company interrogating extrachromosomal DNA (ecDNA) biology to deliver transformative therapies to patients with previously intractable oncogene amplified cancers, reported that the first patient has been dosed with BBI-825 in a first-in-human, Phase 1/2 clinical trial for patients with locally advanced or metastatic cancer with resistance gene amplifications (NCT06299761) (Press release, Boundless Bio, APR 11, 2024, View Source [SID1234642023]). ecDNA are a key driver of high copy number amplification in cancer, and Boundless has validated multiple drug targets that are essential for ecDNA function in cancer cells. BBI-825, the Company’s second ecDNA-directed therapy (ecDTx) to enter clinical trials, is a novel, selective, oral small molecule inhibitor of ribonucleotide reductase (RNR), a rate-limiting enzyme responsible for the de novo synthesis of deoxyribonucleotides, the building blocks of DNA. Boundless has identified an essential role for RNR in ecDNA assembly and repair and in the survival of certain oncogene amplified cancer cells.

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"We are excited to announce dosing of the first patient in our first-in-human study of BBI-825, our second program to enter the clinic," said Klaus Wagner, M.D., Ph.D., Chief Medical Officer at Boundless Bio. "BBI-825 represents a new approach in the potential treatment of oncogene amplifications, particularly in resistance associated with targeted therapy treatment of MAPK pathway-activated cancers."

"Rapid resistance is a major limitation for targeted therapies, particularly in colorectal cancer, as patients with colorectal cancer often progress within about 6 months of initiating targeted treatment," said Rona Yaeger, M.D., Gastrointestinal Oncologist and Early Drug Development Specialist at Memorial Sloan Kettering Cancer Center. "We have observed firsthand that tumors in patients treated with KRASG12C or BRAFV600E targeted therapies develop resistance via MAPK pathway and receptor tyrosine kinase gene amplifications, and those with pre-existing amplifications have an overall worse outcome. There remains an incredible need for therapies that can prevent amplification-driven resistance or treat patients that have already acquired such resistance."

"Advancing our second ecDTx into clinical development is an important milestone for Boundless Bio and underscores the power of our Spyglass platform to identify synthetic lethal targets essential to ecDNA formation and function in oncogene amplified cancers," said Zachary Hornby, President and Chief Executive Officer at Boundless Bio. "We are excited to enroll patients in this first-in-human Phase 1/2 study, focused initially on patients with KRASG12C and BRAFV600E mutated colorectal cancer with resistance gene amplifications. If data are supportive, we may have the opportunity to expand into broader patient populations, including pan-tumor, pan-RAS, and pan-RAF indications, potentially addressing these populations of cancer patients with very high unmet need."

About the STARMAP Trial

STARMAP ("Study Treating Acquired Resistance: MAPK Amplifications") is an open-label, non-randomized, three-part Phase 1/2 clinical trial to evaluate the safety, pharmacokinetics, pharmacodynamic biomarkers, preliminary antitumor activity, and identify the maximum tolerated dose and recommended Phase 2 dose (RP2D) of BBI 825 administered as a single agent or in combination with select targeted therapies (NCT06299761). Part 1 is a dose escalation of BBI-825 as a monotherapy in patients with solid tumors. Part 2 is a combination dose escalation of BBI-825 and targeted therapies, encorafenib and cetuximab, or adagrasib and cetuximab, in patients with advanced or metastatic colorectal cancer with BRAFV600E or KRASG12C mutations, respectively, and co-occurring resistance gene amplifications. Part 3 is a combination dose expansion to evaluate preliminary anti-tumor activity at the RP2D of BBI-825 and each targeted therapy combination from Part 2.

On April 11, 2024 ARTMS Inc. (ARTMS) reported that the acquisition by Telix Pharmaceuticals Limited (Telix) has been completed (Press release, Telix Pharmaceuticals, APR 11, 2024, View Source [SID1234642022]). This acquisition further enhances the vertical integration of Telix’s supply chain and manufacturing by providing a greater level of supply chain and regulatory control over the production of key isotopes.

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ARTMS will support the high efficiency, large-scale and cost-effective production of commercially important medical isotopes for Telix’s portfolio of products, such as zirconium-89 (89Zr), gallium-68 (68Ga), technetium‐99m (99mTc) and copper-64 (64Cu), and will continue to partner with additional radiopharmaceutical companies to ensure that these critical isotopes are available on demand for patients. In addition, ARTMS’ portfolio of advanced cyclotron technologies has immediate application and differentiation for Telix in the production of future commercially important alpha-emitting, therapeutic isotopes, including actinium-225 (225Ac) and astatine-211 (211At).

The history of ARTMS is rooted in a Canadian government funded project focused on solid target production of 99mTc. After that project was successfully completed, the innovation continued and resulted in a full suite of PET products. In 2017, ARTMS Inc. was formed with support and seed funding from Quark Venture, through their Global Health Sciences Fund (GHS) and founding institutions TRIUMF, BC Cancer, Lawson Health Research Institute and the Center for Probe Development. In May of 2020, ARTMS completed a $20M USD Series A fundraising that included GHS and welcomed Deerfield Management to the ARTMS family. In the subsequent years ARTMS has played a critical role in alternative production of medical isotopes with a focus on accelerating the production capabilities of the world’s most commonly installed cyclotrons. The collaboration between ARTMS’ unparalleled team, its investors and founding members has resulted in a truly differentiated organization.

Solomon Partners Securities LLC acted as financial advisor and Norton Rose Fulbright Canada LLP acted as legal advisor to ARTMS during the negotiations and due diligence process related to the acquisition by Telix.

On April 11, 2024 VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease, reported the closing of its previously announced registered direct offering priced at-the-market under Nasdaq rules of 2,272,728 of its common shares and warrants to purchase up to 2,272,728 common shares, at an offering price of $0.88 per common share and associated warrant (Press release, VBI Vaccines, APR 11, 2024, View Source [SID1234642021]). The warrants have an exercise price of $0.76 per share, are exercisable on the date of issuance, and will expire five years following the date of issuance.

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H.C. Wainwright & Co. acted as the exclusive placement agent for the offering.

The gross proceeds to VBI from this offering were approximately $2 million, before deducting the placement agent’s fees and other offering expenses. VBI intends to use the net proceeds from this offering for working capital and general corporate purposes.

A "shelf" registration statement (File Number 333-267109) relating to the securities described above was filed with the Securities and Exchange Commission ("SEC") on August 26, 2022 and was declared effective on September 6, 2022. The offering of the securities in the registered direct offering was made only by means of a prospectus, including a prospectus supplement, forming a part of an effective registration statement. A prospectus supplement and accompanying prospectus relating to the registered direct offering have been filed with the SEC. Electronic copies of the prospectus supplement and accompanying prospectus may be obtained on the SEC’s website at www.sec.gov or by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by phone at (212) 856-5711 or e-mail at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On April 12, 2024 Rakuten Medical, Inc., a global biotechnology company developing and commercializing precision, cell targeting therapies based on its proprietary Alluminox platform, reported a poster presentation of its study to manage edema following photoimmunotherapy at the 115th Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (AACR 2024) in San Diego, California, on April 8th, 2024 (Press release, Rakuten Medical, APR 11, 2024, View Source [SID1234642020]).

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In the study presented in this poster, Rakuten Medical developed a mouse tumor model to assess edema following photoimmunotherapy and evaluated various steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) for edema reduction using the model. As a result, a reduction in edema was observed when the selective COX-2 inhibitor meloxicam, one of NSAIDs, was administered before or after illumination of photoimmunotherapy (30-50% reduction with prophylactic administration, 25% reduction with post-illumination administration). It was also confirmed that the reduction in edema with meloxicam was not associated with a loss of therapeutic benefit based on measurement of tumor growth.

Rakuten Medical’s photoimmunotherapy consists of a drug and a laser light. In pre-clinical studies, local illumination results in highly selective and rapid necrosis of target cells such as tumors. Early clinical studies have shown a manageable safety profile for head and neck cancer.* However, edema is a commonly reported adverse event with severe laryngeal edema noted in some patients, and prophylactic tracheostomy is required if laryngeal edema threatens to obstruct the airway. Thus, new tools to manage edema are needed to reduce the burden on the patient. Based on the results of this study, Rakuten Medical will conduct further research to address the challenges of edema associated with photoimmunotherapy in clinical trials and in clinical practice.

Key findings presented at AACR (Free AACR Whitepaper) 2024
Title: Reduction in photoimmunotherapy-induced edema with COX-2 inhibition: Combatting clinically relevant adverse events without compromising efficacy
Abstract Number: 1415
Abstract Link: View Source!/20272/presentation/5855

Cohorts of mice bearing syngeneic LL/2 tumors engineered to express Ephrin A2 (EphA2) were administered an anti-EphA2 antibody conjugated to IR700 (conjugate) or saline control and illuminated with light. Control mice did not generate edema, but mice treated with conjugate plus light showed a light-dose dependent increase in edema volume which peaked at 6h post light delivery.
Inflammatory cytokine and immune cell populations in the blood and tumor region were then evaluated at the onset (2h post-light), peak (6h), and resolution (24h) of the edema associated with photoimmunotherapy. The results showed a striking increase in neutrophils in the blood at the peak of edema formation (500-fold greater than control mice, n=10, p<0.0001) and a significant increase in IL-6 (n=5, p<0.001) and IL-10 (n=5, p<0.05), indicating the onset of a heightened inflammatory response.
To address edema formation, the effect of steroids or NSAIDs including the selective COX-2 inhibitor meloxicam were evaluated. Results showed that steroids did not reduce edema volume. Meloxicam, one of the selective COX-2 inhibitors, on the other hand, resulted in a reduction in edema volume at all time points and light doses evaluated.
Prophylactic administration (2h prior to light) of meloxicam resulted in a 30-50% reduction in edema at both 2h and 6h post-light illumination. Post-light administration (2h post light) of meloxicam resulted in a 25% reduction at 6h post-light illumination (all settings, n=10, p<0.0001).
The reduction in edema with meloxicam did not have negative impact on tumor growth inhibition.
* Cognetti DM, Johnson JM, Curry JM, et al. Phase 1/2a, open-label, multicenter study of RM-1929 photoimmunotherapy in patients with locoregional, recurrent head and neck squamous cell carcinoma. Head Neck. 2021;43(12):3875-3887. doi:10.1002/hed.26885

On April 11, 2024 J INTS BIO reported the results of its ongoing Phase 1 clinical study of JIN-A02, a 4th generation EGFR-TKI for NSCLC treatment, at the 8th April poster session of the 2024 American Cancer Research Society (AACR) (Free AACR Whitepaper) Annual Meeting held in San Diego, California, from 5th to 10th April (U.S. local time) (Press release, J INTS BIO, APR 11, 2024, View Source;jin-a02-a-novel-oral-4th-generation-egfr-tki-showing-clinical-benefits-in-the-ongoing-phase-1-study-302114115.html [SID1234642019]).

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‘JIN-A02’ is a 4th generation EGFR-TKI targeting C797S mutation that causes resistance to 3rd generation EGFR-TKI (such as Osimertinib, Lazertinib), commonly used in the treatment of NSCLC. ‘JIN-A02’ also targets T790M mutation independently of C797S mutation.

This ongoing Phase 1 clinical study is currently in its 4th Dose Level of 100mg daily and patients have showed increasing clinical benefits with each increasing dose levels. To-date, Partial Response (PR) was confirmed in one subject on the prior dose level of 50mg daily and stable diseases in two other subjects separately in Dose Level 50mg and 25mg daily.

Despite the initial low doses, JIN-A02 has showed clinical benefits immediately, cumulating in a Partial Response at the 3rd Dose Level of 50mg, which is an encouraging result in such an early stage of clinical development, the company explained. Furthermore, JIN-A02 has showed a favorable safety profile with no cardiotoxicity, rash or diarrhea reported, even at the current Dose Level of 100mg daily and the longest duration of treatment is over 8 months and still continuing, the company added. The 5th Dose Level of 150mg daily is expected to begin in 3Q 2024.

J INTS BIO confirmed the favorable safety and efficacy signals of ‘JIN-A02’ with clinical benefits in this poster presentation in San Diego and greater clinical impact is expected as the study progresses.