On March 25, 2024 Edgewood Oncology, a clinical-stage biotechnology company focused on delivering BTX-A51 to patients with hematologic malignancies and genetically-defined solid tumors, reported to have emerged from stealth with $20 million in Series A financing backed by Alta Partners to advance the clinical development of BTX-A51 in acute myeloid leukemia (AML) and a precision medicine approach to breast cancer (Press release, Edgewood Oncology, MAR 25, 2024, View Source [SID1234641424]). BTX-A51 is a first-in-class, small molecule, multi-kinase inhibitor of casein kinase 1 alpha (CK1), cyclin-dependent kinase 7 (CDK7) and CDK9 that synergistically co-targets master regulators of cancer to promote programmed cell death, or apoptosis.

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Edgewood acquired the rights to BTX-A51 from Yissum, the technology transfer company of The Hebrew University of Jerusalem, in 2023 and will use the Series A funding to advance efficacy studies in AML and breast cancer.

"We formed Edgewood Oncology because of the synergistic mechanism of action and promising safety and anti-tumor data that was observed with BTX-A51 in Phase 1 in AML and solid tumor patients. We look forward to further developing this compound using a precision medicine approach in patient populations who lack effective treatment options," said David N. Cook, Ph.D., chief executive officer, Edgewood Oncology. "Furthermore, we have taken a virtual approach to drug development, which allows us to remain highly-focused, agile and efficient as we advance this investigational compound in the clinic."

Testing the Use of Combination Therapy in AML

There exists a significant unmet need for improved first-line regimens in AML as well as for patients with relapsed or refractory (R/R) disease. In a Phase 1 study in heavily pre-treated R/R AML patients, monotherapy BTX-A51 demonstrated a favorable safety profile and encouraging antileukemic activity. As a next step, Edgewood initiated a study of BTX-A51 in combination with azacitidine in R/R AML patients in December 2023. The aim of this Phase 2, multicenter, open-

label study is to evaluate the response rate (CR, CRh and CRi) as well as the safety, toxicity and pharmacokinetics of BTX-A51 in combination with azacitidine in patients with R/R AML.

"We’re incredibly excited about the potential of BTX-A51in this patient population, and we also have good reason to believe that BTX-A51 could be complementary to standard of care in first-line unfit AML," said Zung Thai, M.D., Ph.D., chief medical officer, Edgewood Oncology. "In Phase 1 monotherapy, we observed several complete responses and a wide therapeutic window and our preclinical data also suggest that BTX-A51 acts synergistically with both azacitidine and venetoclax in human leukemia cells and animal models."

Edgewood is expecting to initiate a Phase 2 study in breast cancer in patients with a genetically-defined profile in Q2 2024.

Leadership Team Comprised of Seasoned Biotech Veterans

"Edgewood’s leadership team not only has a strong track record in company formation and drug development, but Dr. Thai brings an in-depth understanding of BTX-A51, having led all clinical and regulatory efforts for this program during his tenure at BiotheryX," said Dan Janney, managing partner, Alta Partners. "Moreover, we believe Edgewood’s virtual approach to drug development is the best strategy to get innovative new medicines to patients as quickly and efficiently as possible."

The executive team includes Dr. Cook as chief executive officer, and Dr. Thai as chief medical officer. BTX-A51’s scientific founder is Yinon Ben-Neriah, M.D., Ph.D., professor of Immunology and Cancer Research, The Hebrew University of Jerusalem. The company’s board of directors includes Dr. Cook, Dan Janney, and Isan Chen, M.D., a noted clinical oncologist and co-founder, president and chief executive officer, MBrace Therapeutics, Inc.

On March 25, 2024 Biodesix, Inc. (Nasdaq: BDSX), a leading diagnostic solutions company with a focus in lung diseases, reported that it has entered into a new master collaborative research agreement (MCRA) with Memorial Sloan Kettering Cancer Center (MSK) under which the teams will collaborate on a development plan for diagnostic tests aimed at improving the treatment of cancer (Press release, Biodesix, MAR 25, 2024, View Source [SID1234641423]).

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Biodesix will utilize its array of genomics, proteomics, and data mining capabilities with the aim of developing and commercializing oncology biomarker assays in collaboration with MSK. Bio-Rad will provide its industry-leading digital PCR assay technology in support of this important work.

The collaborators, represented by Dr. Howard Scher (MSK) and Dr. Gary Pestano (Biodesix), will share an update at the 31st International Precision Medicine Tri-Con meeting (PMTC) on March 25: "An Industry | Academic Collaboration Framework Focused on Novel Diagnostic Test Development in Oncology".

"The expansion of our previous master sponsored research agreement (MSRA) into a master collaborative research agreement with MSK is a significant milestone for Biodesix and for biomarkers in oncology diagnostics. Biodesix looks forward to co-developing and validating new test concepts under these agreements," said Scott Hutton, CEO, Biodesix.

"We look forward to working with Biodesix to develop the next generation of highly multiplexed digital PCR assays as part of our expanding oncology offering," said Simon May, EVP and President of Life Sciences at Bio-Rad Laboratories. "Bio-Rad provides the leading solution for digital PCR, and we are committed to providing oncology researchers and commercial partners with technologies that enable everything from biomarker discovery to clinical trials and patient monitoring of minimal residual disease.

On March 25, 2024 Nuvation Bio Inc. (NYSE: NUVB), a biopharmaceutical company tackling some of the greatest unmet needs in oncology by developing differentiated and novel therapeutic candidates, and AnHeart Therapeutics Ltd. (AnHeart), a global clinical-stage biopharmaceutical company developing novel precision therapies for people with cancer, reported that the companies have entered into a definitive agreement for Nuvation Bio to acquire AnHeart in an all-stock transaction (the Acquisition) (Press release, Nuvation Bio, MAR 25, 2024, View Source [SID1234641422]). Immediately following the closing of the Acquisition, the former shareholders of AnHeart will own approximately 33% and the current stockholders of Nuvation Bio will own approximately 67% of Nuvation Bio on a fully diluted basis. The Acquisition, which has been approved by the board of directors of each company and is subject to approval by AnHeart’s shareholders and other customary closing conditions, will position Nuvation Bio as a late-stage global oncology company with multiple programs in clinical development. The Acquisition is expected to close in the second quarter of 2024.

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"This transaction represents a significant milestone for our company and reflects Nuvation Bio’s continued commitment to developing therapies for patients with the most difficult-to-treat cancers," said David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio. "AnHeart’s lead asset, taletrectinib, which will become our lead asset as it completes two pivotal studies, is a differentiated, next-generation ROS1 inhibitor with a potentially best-in-class profile that may overcome the significant limitations of existing therapies. We are impressed by what the AnHeart team has done to develop this asset and intend to build on the progress made to date."

Dr. Hung added, "Nuvation Bio is well capitalized, and this all-stock transaction maintains our robust cash balance and removes any need for near-term financing to develop both new assets and our current pipeline. With our combined talented teams and resources, we will continue to focus on executing the development strategy for our differentiated pipeline. We expect this deal will bring Nuvation Bio much closer to realizing our goal of delivering novel cancer therapies to patients, and we look forward to this exciting next chapter together with the AnHeart team."

"AnHeart, named for our deep sense of service to patients, has worked tirelessly over the past five years to advance our pipeline of next-generation precision oncology medicines. We are excited to continue our mission as part of Nuvation Bio given their shared vision to improve the lives of people with cancer," said Junyuan Jerry Wang, Ph.D., Co-Founder and Chief Executive Officer of AnHeart. "We believe the pipeline and financial strength of the combined company have the potential to create a market leader, and we look forward to working with David and the Nuvation Bio team to bring new cancer therapies to patients in need of better options."

Management and Organization

Nuvation Bio will continue to be led by its current management team, including David Hung, M.D., its Founder, Chief Executive Officer, and President, and expects AnHeart’s employees in China and the United States to join the Nuvation Bio team. Following the closing of the Acquisition, Min Cui, Ph.D., Founder and Managing Director of Decheng Capital, an investor in AnHeart, and Junyuan Jerry Wang, Ph.D., Co-Founder and Chief Executive Officer of AnHeart, will join the Nuvation Bio board of directors.

Transaction Details

At the closing of the Acquisition, Nuvation Bio will issue to the AnHeart securityholders, in exchange for all outstanding AnHeart shares, options, and other securities, approximately 43,590,197 shares of Nuvation Bio’s Class A common stock (inclusive of the shares of Class A common stock underlying the AnHeart equity awards to be assumed by Nuvation Bio), 851,212 shares of Nuvation Bio’s Series A Non-Voting Convertible Preferred Stock, and warrants collectively exercisable for 2,893,731 shares of Nuvation Bio’s Class A common stock at an exercise price of $11.50 per share.

Subject to approval by the Nuvation Bio stockholders (the Nuvation Bio Stockholder Approval), each share of Series A Non-Voting Convertible Preferred Stock issued by Nuvation Bio in the Acquisition will initially be convertible into 100 shares of Class A common stock. Additionally, the warrants issued in the Acquisition will be restricted until receipt of the Nuvation Bio Stockholder Approval. Any shareholders of AnHeart who are not accredited investors will receive cash for their AnHeart shares in lieu of receiving Nuvation Bio securities.

The holders of approximately 90% of AnHeart’s outstanding shares have entered into voting agreements, pursuant to which they have agreed to, among other matters, vote in favor of the Acquisition.

In connection with the execution of the definitive merger agreement, Dr. Hung entered into a voting agreement, pursuant to which he agreed to vote his shares of Nuvation Bio stock, representing approximately 27% of Nuvation Bio’s outstanding shares, for the Nuvation Bio Stockholder Approval. The closing of the Acquisition does not require the approval of the Nuvation Bio stockholders.

Nuvation Bio and AnHeart intend that the Acquisition will qualify as a tax-free reorganization. As AnHeart’s parent company after the Acquisition, Nuvation Bio will own all of AnHeart’s assets, including AnHeart’s intellectual property.

For further information regarding the terms and conditions contained in the definitive transaction agreement, please see Nuvation Bio’s current report on Form 8-K, which will be filed with the U.S. Securities and Exchange Commission (the SEC) in connection with the Acquisition.

Pipeline Updates

Taletrectinib is being evaluated for the treatment of patients with ROS1-positive NSCLC in two pivotal Phase 2 studies, TRUST-I (NCT04395677) in China and TRUST-II (NCT04919811), a global pivotal study. Nuvation Bio will continue to advance both studies.
Taletrectinib has been granted Breakthrough Therapy Designations by the U.S. Food and Drug Administration (FDA) and China’s National Medical Products Administration (NMPA) for the treatment of advanced or metastatic ROS1-positive NSCLC.
The NMPA has accepted and granted Priority Review Designation to New Drug Applications for taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC who either have or have not previously been treated with ROS1 TKIs.
Nuvation Bio will continue to develop safusidenib, a novel, selective, potent, oral mIDH1 inhibitor being evaluated by AnHeart in a global Phase 2 study (NCT05303519) in patients with grades 2 and 3 IDH1-mutant glioma.
Nuvation Bio will continue to advance all clinical studies for its internally discovered pipeline candidates, including the Phase 1b studies of NUV-868 and the recently initiated Phase 1/2 study of NUV-1511.
Conference Call

Nuvation Bio will schedule a conference call to discuss the acquisition after it has closed.

Advisors

Evercore is acting as Nuvation Bio’s exclusive financial advisor and Cooley LLP is acting as legal counsel, alongside Morrison & Foerster LLP as intellectual property counsel, Haiwen & Partners as Chinese legal counsel, and Conyers as Cayman Islands legal counsel. Davis Polk & Wardwell LLP is acting as legal counsel for AnHeart, alongside Fangda Partners as Chinese legal counsel and Walkers (Cayman) LLP as Cayman Islands legal counsel.

On March 25, 2024 ONO Pharmaceuticals, Co., Ltd. reported it has completed target patient enrollment of the first arm (Part A) of the PROSPECT Study, a Phase 2 clinical trial evaluating the safety and efficacy of tirabrutinib (ONO-4059) in U.S. patients with relapsed or refractory primary central nervous system lymphoma (R/R PCNSL) (Press release, Ono, MAR 25, 2024, View Source [SID1234641421]).

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"A PCNSL diagnosis can be frightening for patients, and treatment options approved by the FDA are critically needed in the U.S.," said Kiyoaki Idemitsu, Executive Officer / Executive Director, Clinical Development of ONO PHARMA. "Completing enrollment of the first arm of this U.S. study is an important step in bringing a therapeutic option to patients with R/R PCNSL in the U.S. We are very grateful to everyone involved with this clinical trial."

The first arm (Part A) of the PROSPECT Study is evaluating the safety and efficacy of tirabrutinib in patients with R/R PCNSL who received previous treatment with high-dose methotrexate-based regimens. Enrollment is now complete for Part A. ONO PHARMA continues to enroll newly diagnosed and previously untreated PCNSL patients in the second arm of the study (Part B), evaluating tirabrutinib in combination with one of two high-dose methotrexate-based regimens as first-line therapy in the PROSPECT Study (theprospectstudy.com and clinicaltrials.gov).

PCNSL is a rare and aggressive extranodal non-Hodgkin lymphoma with historically poor survival rates.1 PCNSL affects the brain, its protective membranes, the spinal cord, and/or eye, without systemic involvement at the time of diagnosis.1 In the U.S., the incidence of PCNSL is approximately five out of 1,000,000 people per year, with higher rates in people over 65 years old.2

Tirabrutinib is a highly selective irreversible Bruton’s tyrosine kinase inhibitor discovered by ONO PHARMA in Japan. In March 2023, the U.S. Food and Drug Administration granted Orphan Drug Designation to tirabrutinib for the treatment of PCNSL.3 Tirabrutinib is currently approved for R/R PCNSL treatment in Japan, Taiwan, and South Korea.3

"This is an important milestone for ONO as it builds its clinical trial program in the U.S.," said Kunihiko Ito, President and CEO of ONO PHARMA USA. "For decades, ONO’s commitment to innovation in oncology has helped change treatment paradigms for patients all over the world. We look forward to continuing this legacy as we investigate tirabrutinib for PCNSL in the U.S."

About PCNSL
PCNSL is a rare and aggressive extra nodal non-Hodgkin lymphoma (NHL) that is confined to the brain parenchyma, spinal cord, eye, or leptomeninges, without systemic involvement. The annual incidence rate of PCNSL is approximately five cases per 1,000,000 people in the U.S. The rate can further increase among immunocompetent people aged 65 years and older. The signs and symptoms presented in patients with PCNSL vary depending on the neuroanatomical site of the lesion, and include cranial neuropathy, neuropsychiatric symptoms, symptoms associated with increased intracranial pressure, seizures, ocular symptoms, headache, dysmotility, cranial neuropathy, and radiculopathy. There are no therapeutic products approved for the treatment of PCNSL in the U.S., and data guiding therapeutic approaches are very limited. Despite recent progress resulting in the improvement of clinical outcomes in newly diagnosed patients with PCNSL after an induction treatment, approximately 20 to 30 percent of patients are refractory to the initial treatment, and up to 60 percent of patients will eventually relapse. To learn more about R/R PCNSL, please visit navigatingpcnsl.com.

About Tirabrutinib
Tirabrutinib, discovered and developed by Ono Pharmaceutical Co., Ltd. is a highly potent selective BTK inhibitor. Signaling through the B-cell receptor (BCR) regulates cellular proliferation and activation, and promotes survival, differentiation, and clonal expansion of B-cells. The BCR signaling pathway plays an important role in a number of B-cell malignancies. Gene expression profiling data revealed BCR signaling as the most prominent pathway activated in chronic lymphocytic leukemia (CLL) cells isolated from lymphatic tissues. In Japan, tirabrutinib was approved in March 2020 for the treatment of relapsed or refractory PCNSL and launched under the tradename of Velexbru in May 2020. In addition, tirabrutinib was approved for the treatment of relapsed or refractory PCNSL in South Korea in November 2021 and in Taiwan in February 2022. Moreover, Velexbru was approved for the treatment of Waldenstrom macroglobulinemia and lymphoplasmacytic lymphoma in Japan in August 2020.

About the PROSPECT Study
The PROSPECT Study is a Phase 2 trial (NCT04947319) evaluating the safety and effectiveness of an investigational oral medicine called tirabrutinib for the potential treatment of newly diagnosed or relapsed/refractory (R/R) primary central nervous system lymphoma (PCNSL), which is a type of cancer that either does not improve from treatment (refractory) or improves only for a limited time (relapsed). Current treatment options for R/R PCNSL are limited, and there are no medications approved in the U.S. for the treatment of PCNSL. Learn more about the PROSPECT Study here: theprospectstudy.com.

On March 25, 2024 Bio-Thera Solutions (688177:SH), a commercial-stage biopharmaceutical company developing a pipeline of innovative therapies and biosimilars, reported receiving IND clearance from the US FDA for a phase II Study for BAT8006, an innovative Antibody Drug Conjugate (ADC) targeting Folate Receptor α (FRα) (Press release, BioThera Solutions, MAR 25, 2024, View Source;302098092.html [SID1234641420]). The phase II study will investigate the use of BAT8006 for the treatment of subjects with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer.

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FRα is a folic acid-binding protein located on cell membranes that is overexpressed in a variety of solid tumors such as ovarian, lung, breast cancer, etc., but has a limited distribution and a lower level of expression in normal tissues. This differential expression makes FRα an attractive target for cancer drug development. BAT8006 is developed using Bio-Thera’s proprietary anti-FRα antibody and proprietary ADC linker-payload combination that includes a systemically stable and cleavable linker and a small molecule topoisomerase I inhibitor. Preclinical studies have shown that BAT8006 demonstrates good stability and safety along with strong anti-tumor activity. The small molecule topoisomerase I inhibitor payload carried by BAT8006 has a strong cell membrane penetration ability, which enables the payload to kill nearby cancer cells after the cancer cells initially targeted by the ADC are killed. This bystander effect gives BAT8006 the potential to effectively overcome the heterogeneity of the tumor. Currently, a phase I study of BAT8006 is ongoing in China. In that trial, the dose escalation study has completed and the dose expansion and dose optimization study in a series of tumors are ongoing. The preliminary data indicated that BAT8006 could potentially be a best-in-class drug. Updated clinical data will be presented at future academic conference.