On September 19, 2023 Boundless Bio, a clinical stage, next-generation precision oncology company interrogating extrachromosomal DNA (ecDNA) biology to deliver transformative therapies to patients with previously intractable oncogene amplified cancers, reported a clinical trial collaboration and supply agreement with Eli Lilly and Company for supply of their CDK4/6 inhibitor Verzenio (abemaciclib) for use in combination with BBI-355 in a clinical trial of patients with locally advanced or metastatic solid tumors with oncogene amplifications (Press release, Boundless Bio, SEP 19, 2023, View Source [SID1234635266]). BBI-355 is an orally administered, novel, selective small molecule inhibitor of CHK1 and represents what Boundless Bio believes is the first ecDNA-directed therapy (ecDTx) in development for oncogene amplified cancers.

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"We are pleased to enter this supply agreement with Lilly to evaluate the combination of BBI-355 and abemaciclib in patients with ecDNA-driven solid tumors harboring CDK4 or CDK6 amplifications in our ongoing POTENTIATE trial," said Zachary Hornby, President and Chief Executive Officer of Boundless Bio. "To date, CDK4/6 inhibitors have only been approved in HR+/HER2- breast cancer. Based on preclinical data, we believe BBI-355 has the potential to disable the underlying ecDNA driving oncogene amplification and unlock synergistic anti-tumor activity when combined with abemaciclib, potentially providing an important new treatment option for patients with CDK4 or CDK6 amplified solid tumors."

Under the terms of the agreement, Lilly will provide abemaciclib clinical drug supply at no cost for Boundless Bio’s ongoing Phase 1/2 clinical trial (POTENTIATE), which will assess BBI-355 in combination with certain selected targeted therapies, including abemaciclib, in patients with specific oncogene amplified solid tumors.

About the POTENTIATE Trial

BBI-355 is being evaluated in a first-in-human Phase 1/2 clinical trial ("POTENTIATE": Precision Oncology Trial Evaluating Novel Therapeutic Interrupting Amplifications Tied to ecDNA) in patients with locally advanced or metastatic solid tumors with oncogene amplifications, whose disease has progressed despite all standard therapies or for whom no further standard or clinically acceptable therapy exists.

The open-label, non-randomized, 3-part trial involves: BBI-355 single agent dose escalation and expansion in cancer patients with oncogene amplification, dose escalation of BBI-355 in combination with certain selected targeted therapies in cancer patients with specific oncogene amplifications, and dose expansion of BBI-355 in combination with certain selected targeted therapies in cancer patients with specific oncogene amplification on ecDNA. BBI-355 is administered orally every other day. In part 3 of the trial, an ecDNA diagnostic clinical trial assay (CTA), which we call ECHO (ecDNA Harboring Oncogenes), will be implemented to determine the presence of oncogenes amplified on ecDNA in patient tumor samples. ECHO is a proprietary bioinformatic diagnostic algorithm designed by Boundless Bio and developed into a CTA in collaboration with SOPHiA GENETICS to detect oncogenes amplified on ecDNA from tumor biopsy samples using routine clinical NGS assays.

About BBI-355

BBI-355 is an orally administered, novel, selective checkpoint kinase 1 (CHK1) inhibitor and, what we believe, is the first ecDNA-directed therapy (ecDTx) being investigated to treat patients with oncogene amplified cancer. CHK1 is a master regulator of the cellular response to DNA replication stress (RS), which frequently arises from oncogene amplification on ecDNA. By disrupting proper CHK1 function in oncogene amplified cancer cells, we believe BBI-355 facilitates catastrophic RS, and preferentially kills cancer cells relative to healthy cells. CHK1 was identified as an ecDNA essential target via Boundless Bio’s proprietary Spyglass research platform.

On September 19, 2023 BostonGene reported an agreement with Hokkaido University Hospital to drive the discovery, validation and implementation of a groundbreaking stratification protocol for HER2-positive breast cancer patients (Press release, BostonGene, SEP 19, 2023, https://www.businesswire.com/news/home/20230918064199/en/BostonGene-and-Hokkaido-University-Hospital-Collaborate-to-Develop-Novel-HER2-Protocols-for-Breast-Cancer [SID1234635265]).

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Located in Sapporo, Japan, Hokkaido University Hospital stands as one of the most prominent medical institutions in the country. Affiliated with Hokkaido University School of Medicine, the hospital offers both high-quality patient care and cutting-edge medical research with an international perspective. As an academic hospital, it is also committed to the mentorship and development of upcoming medical professionals through expansive training programs.

Conventional HER2-targeted antibodies, such as trastuzumab and pertuzumab, fall short in treating patients with HER2-low breast cancer. However, recent clinical trials have demonstrated that trastuzumab-deruxtecan, an antibody-drug conjugate targeting HER2, benefits these patients. Additional data are required to elucidate the best approach for identifying HER2-low patients likely to benefit from the novel therapy. A growing interest lies in the RNA-based method, which can simultaneously investigate the tumor microenvironment and HER2 expression levels. This collaboration aims to demonstrate the benefits of the methodology that interrogate the impacts of the tumor immune ecosystem on HER2-targeted therapy. In this study, BostonGene will apply its genomics pipeline to reveal key tumor drivers, including immune microenvironment properties and genomic biomarkers of response to diverse therapies. In addition, the BostonGene-developed unique and robust machine learning algorithm named Kassandra will digitally reconstruct the tissue tumor microenvironment and cellular composition to identify distinct cell populations. The joint research will be led by Professors Ichiro Kinoshita, MD, PhD at the Division of Clinical Cancer Genomics/Department of Medical Oncology and Masato Takahashi, MD, PhD at the Department of Breast Surgery, Hokkaido University Hospital.

"We are excited to enter into this partnership with BostonGene to fully understand the molecular profiles of our patients. BostonGene’s comprehensive solutions have the potential to deliver breakthrough discoveries and help us identify novel treatment approaches," said Ichiro Kinoshita, MD, PhD.

"Breast cancer ranks as the primary cause of cancer in women across the country. Enhancing treatment outcomes remains a critical focus. Through the findings of this research, we aim to advance technologies that offer more precise medical care and minimize the recurrence of breast cancer in as many patients as possible," said Masato Takahashi, MD, PhD.

"We’re honored to partner with Hokkaido University providing our AI-based molecular and immune profiling to uncover treatable targets to personalize therapy for breast cancer patients," said Nathan Fowler, MD, Chief Medical Officer at BostonGene. "This collaboration supports our mission to equip doctors in finding the most effective treatment options for their patients."

BostonGene, NEC Corporation and Japan Industrial Partners recently announced the formation of BostonGene Japan Inc., a Tokyo-based joint venture to advance personalized medicine and dramatically improve patient outcomes. The company will utilize BostonGene’s high-complexity molecular technology and advanced biocomputational algorithms to accelerate the development and validation of novel precision medicine approaches.

BostonGene will participate in the 82nd Annual Meeting of the Japanese Cancer Association (JCA) at Pacific Convention Plaza Yokohama from September 21 to September 23. Please contact Erin O’Reilly to learn more or to schedule a meeting.

On September 19, 2023 A recently published paper in the International Journal of Radiation Oncology – Biology – Physics (Red Journal) reported encouraging results from a multicenter clinical study conducted with Humanetics Corporation’s (Humanetics) novel radioprotective drug, BIO 300, in patients with non-small cell lung cancer (NSCLC) (Press release, Humanetics, SEP 19, 2023, View Source [SID1234635264]). Radiation therapy is a vital component of cancer treatment, delivering targeted doses of radiation to tumor sites to eliminate cancer cells. However, the challenge lies in minimizing the damage from radiation to surrounding healthy tissues, which can lead to debilitating side effects and limit treatment options. Humanetics aims to address this critical issue with BIO 300, which can safeguard normal tissues during radiotherapy without protecting the tumor, thereby enhancing patient outcomes and quality of life.

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Twenty-one patients were enrolled in the phase 1b/2a study evaluating the safety and clinical utility of BIO 300 as a radioprotector of normal tissues in patients with NSCLC (NCT02567799). The study was a nonrandomized, open-label, single-arm, ascending dose study in NSCLC patients prescribed concurrent radiotherapy and chemotherapy. Patients self-administered BIO 300 orally once daily starting before initiating radiotherapy and continued for the entire 6-7 week course of concurrent chemoradiotherapy. The primary endpoint was acute dose-limiting toxicities attributable to BIO 300. Secondary outcomes included pharmacokinetics, pharmacodynamics, overall toxicity profile, quality of life, local response rate, and survival.

The study found that BIO 300 was safe and well tolerated, and no dose-limiting toxicities were reported. Patient-reported quality of life and body weight were stable throughout the study period. The tumor response rate was 65%, with a complete response rate of 20%. BIO 300 did not alter the pharmacokinetics of standard chemotherapy. Serum TGFβ1, a pro-inflammatory/pro-fibrotic cytokine implicated in pulmonary fibrosis and radiation pneumonitis, was reduced in a dose-dependent manner across cohorts. In addition, patients receiving BIO 300 had a lower rate of hematological, pulmonary, and gastrointestinal toxicities compared to previous clinical studies with the same chemoradiotherapy regimen in the absence of BIO 300.

The pharmacodynamic results, combined with the tumor response and low toxicity rates, support further investigation of BIO 300 as an effective radioprotective drug in patients with NSCLC.

Ronald J. Zenk, CEO at Humanetics, expressed his enthusiasm regarding the clinical trial results, stating, "Showing that BIO 300 is safe and may protect normal lung tissues in NSCLC patients without compromising concurrent chemoradiotherapy has the potential to reform current cancer treatment. By reducing the risk of debilitating side effects, BIO 300 has the potential to improve quality of life for cancer patients undergoing radiation therapy."

BIO 300 is also under advanced development as a radiation medical countermeasure for the military and first responders, and BIO 300 is in a phase 2b trial evaluating the clinical utility of BIO 300 to protect lung tissues against the long-term effects of COVID-19 (NCT04482595).

On September 19, 2023 A recently published paper in the International Journal of Radiation Oncology – Biology – Physics (Red Journal) reported encouraging results from a multicenter clinical study conducted with Humanetics Corporation’s (Humanetics) novel radioprotective drug, BIO 300, in patients with non-small cell lung cancer (NSCLC) (Press release, Humanetics, SEP 19, 2023, View Source [SID1234635264]). Radiation therapy is a vital component of cancer treatment, delivering targeted doses of radiation to tumor sites to eliminate cancer cells. However, the challenge lies in minimizing the damage from radiation to surrounding healthy tissues, which can lead to debilitating side effects and limit treatment options. Humanetics aims to address this critical issue with BIO 300, which can safeguard normal tissues during radiotherapy without protecting the tumor, thereby enhancing patient outcomes and quality of life.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Twenty-one patients were enrolled in the phase 1b/2a study evaluating the safety and clinical utility of BIO 300 as a radioprotector of normal tissues in patients with NSCLC (NCT02567799). The study was a nonrandomized, open-label, single-arm, ascending dose study in NSCLC patients prescribed concurrent radiotherapy and chemotherapy. Patients self-administered BIO 300 orally once daily starting before initiating radiotherapy and continued for the entire 6-7 week course of concurrent chemoradiotherapy. The primary endpoint was acute dose-limiting toxicities attributable to BIO 300. Secondary outcomes included pharmacokinetics, pharmacodynamics, overall toxicity profile, quality of life, local response rate, and survival.

The study found that BIO 300 was safe and well tolerated, and no dose-limiting toxicities were reported. Patient-reported quality of life and body weight were stable throughout the study period. The tumor response rate was 65%, with a complete response rate of 20%. BIO 300 did not alter the pharmacokinetics of standard chemotherapy. Serum TGFβ1, a pro-inflammatory/pro-fibrotic cytokine implicated in pulmonary fibrosis and radiation pneumonitis, was reduced in a dose-dependent manner across cohorts. In addition, patients receiving BIO 300 had a lower rate of hematological, pulmonary, and gastrointestinal toxicities compared to previous clinical studies with the same chemoradiotherapy regimen in the absence of BIO 300.

The pharmacodynamic results, combined with the tumor response and low toxicity rates, support further investigation of BIO 300 as an effective radioprotective drug in patients with NSCLC.

Ronald J. Zenk, CEO at Humanetics, expressed his enthusiasm regarding the clinical trial results, stating, "Showing that BIO 300 is safe and may protect normal lung tissues in NSCLC patients without compromising concurrent chemoradiotherapy has the potential to reform current cancer treatment. By reducing the risk of debilitating side effects, BIO 300 has the potential to improve quality of life for cancer patients undergoing radiation therapy."

BIO 300 is also under advanced development as a radiation medical countermeasure for the military and first responders, and BIO 300 is in a phase 2b trial evaluating the clinical utility of BIO 300 to protect lung tissues against the long-term effects of COVID-19 (NCT04482595).

On September 19, 2023 RayzeBio, Inc. (Nasdaq: RYZB), a targeted radiopharmaceutical company developing an innovative pipeline against validated solid tumor targets, reported the closing of its previously announced upsized $358 million initial public offering (IPO) of 19,869,240 shares of common stock, including the full exercise of the underwriters’ option to purchase up to 2,591,640 additional shares from RayzeBio, at a price to the public of $18.00 per share (Press release, RayzeBio, SEP 19, 2023, View Source [SID1234635263]). RayzeBio sold 18,706,240 shares of common stock and the selling stockholder named in the prospectus sold 1,163,000 shares of common stock. RayzeBio did not receive any proceeds from the sale of shares by the selling stockholder. The aggregate gross proceeds to RayzeBio from the offering, before deducting underwriting discounts and commissions and other offering expenses payable by RayzeBio, were approximately $336.7 million. The shares began trading on The Nasdaq Global Market on September 15, 2023 under the symbol "RYZB."

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J.P. Morgan, Jefferies, Evercore ISI and Truist Securities acted as joint book-running managers for the offering.

Registration statements relating to these securities have been filed with the U.S. Securities and Exchange Commission (SEC) and became effective on September 14, 2023. A copy of the registration statements can be accessed through the SEC’s website at www.sec.gov. This offering was made only by means of a prospectus forming part of the registration statements relating to these securities. A copy of the final prospectus relating to this offering may be obtained from: J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (866) 803-9204, or by email at [email protected]; Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, NY 10022, or by telephone at (877) 821-7388, or by email at [email protected]; Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 35th Floor, New York, NY 10055, by telephone at (888) 474-0200, or by email at [email protected]; and Truist Securities, Inc., Attention: Prospectus Department, 3333 Peachtree Road NE, 9th floor, Atlanta, GA 30326, or by telephone at (800) 685-4786, or by email at [email protected].

This press release shall not constitute an offer to sell, or a 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 the registration or qualification under the securities laws of any such state or jurisdiction.