On September 22, 2023 Astrazeneca and Daiichi Sankyo reported Positive high-level results from the TROPION-Breast01 Phase III trial showed datopotamab deruxtecan (Dato-DXd) demonstrated a statistically significant and clinically meaningful improvement for the primary endpoint of progression-free survival (PFS) compared to investigator’s choice of chemotherapy in patients with inoperable or metastatic hormone receptor (HR)-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously treated with endocrine-based therapy and at least one systemic therapy (Press release, AstraZeneca, SEP 22, 2023, View Source [SID1234635319]).

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A trend in improvement for the dual primary endpoint of overall survival (OS) was observed for datopotamab deruxtecan versus chemotherapy. Data for OS were not mature at this interim analysis and the trial will continue as planned to assess OS.

The safety profile of datopotamab deruxtecan was consistent with previous clinical trials in breast cancer with no new safety signals identified. All grade interstitial lung disease rates were low.

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "Today’s TROPION-Breast01 news is a significant development for patients with HR-positive, HER2-low or negative metastatic breast cancer whose tumours have become insensitive to endocrine therapy and who currently face poor outcomes. We are encouraged by these positive results."

Ken Takeshita, MD, Global Head, Oncology R&D, Daiichi Sankyo, said: "The positive topline results from TROPION-Breast01 demonstrate the potential for datopotamab deruxtecan to become an important treatment option for patients with HR-positive, HER2-low or HER2-negative breast cancer in the second-line metastatic setting. We look forward to realising the full potential of this TROP2-directed antibody drug conjugate across breast cancer subtypes through our ongoing Phase III programme, including two trials in patients with triple-negative breast cancer."

More than two million people worldwide are diagnosed with breast cancer each year.1 HR-positive, HER2-low or negative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases.1,2 Standard initial treatment for these patients is endocrine therapy but most patients with advanced disease will develop resistance, underscoring the need for additional options.3,4 TROP2 is a protein broadly expressed in HR-positive, HER2-low or negative breast cancer.5,6

The data will be presented at a forthcoming medical meeting and shared with health authorities.

AstraZeneca and Daiichi Sankyo have two additional Phase III trials evaluating datopotamab deruxtecan in breast cancer. TROPION-Breast02 is comparing datopotamab deruxtecan to chemotherapy in patients with previously untreated locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) who are not candidates for anti-PDL1 therapy. TROPION-Breast03 is evaluating datopotamab deruxtecan with and without Imfinzi (durvalumab) versus investigator’s choice of therapy in patients with Stage I-III TNBC with residual disease after neoadjuvant therapy.

Notes

HR-positive breast cancer
Breast cancer is the most common cancer in the world and a leading cause of cancer-related death.1 More than two million breast cancer cases were diagnosed in 2020 with nearly 685,000 deaths globally.1

Breast cancer is considered HR-positive, HER2-low or negative when tumours test positive for oestrogen and/or progesterone hormone receptors and negative or low for HER2 (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-).2,7 HR-positive, HER2-low or negative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases.2 Approximately 30% of patients diagnosed with HR-positive, HER2-low or negative metastatic breast cancer are expected to live five years after their diagnosis.2

TROP2 is a protein broadly expressed in several solid tumours, including HR positive, HER2-low or negative breast cancer.5 TROP2 expression is associated with increased tumour progression and poor survival in patients with breast cancer.5,6

TROPION-Breast01
TROPION-Breast01 is global, randomised, multicentre, open-label Phase III trial evaluating the safety and efficacy of datopotamab deruxtecan versus investigator’s choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in patients with inoperable or metastatic HR- positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have previously progressed on or are not suitable for endocrine therapy per investigator assessment.

The dual primary endpoints of TROPION-Breast01 are PFS as assessed by blinded independent central review (BICR) and OS. Key secondary endpoints include objective response rate, duration of response, investigator-assessed PFS, disease control rate and time to first subsequent therapy.

TROPION-Breast01 enrolled more than 700 patients at sites in Asia, Europe, North America, South America and Africa. For more information visit ClinicalTrials.gov.

Datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, datopotamab deruxtecan is one of five lead ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

A comprehensive development programme is underway globally with more than 12 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple tumours, including non-small cell lung cancer, triple-negative breast cancer and hormone receptor-positive, HER2-low or negative breast cancer. Beyond the TROPION programme, datopotamab deruxtecan is also being evaluated in novel combinations in several ongoing trials. AstraZeneca is also researching a potential diagnostic test to help identify patients most likely to benefit from treatment with datopotamab deruxtecan.

On September 21, 2023 Abpro Corporation ("Abpro"), a biotechnology company with the mission of improving the lives of those facing severe and life-threatening diseases with next-generation antibody therapies, and Atlantic Coastal Acquisition Corp. II (NASDAQ: ACAB), a special purpose acquisition corporation ("Atlantic Costal"), reported a term sheet to enter into a definitive business combination, which was entered into on September 18, 2023 (Press release, Abpro Therapeutics, SEP 21, 2023, View Source [SID1234639032]). The transaction is expected to close in Q2 of 2024 and would result in an implied equity valuation for Abpro of $725 million.

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"This is a milestone for Abpro, and we look forward to working with Atlantic Coastal and its team," said Ian Chan, CEO and co-founder of Abpro. "The proceeds we expect to raise in connection with this transaction will help accelerate the advancement of our pipeline toward clinical trials and provide the foundation for ongoing development of novel immunotherapies to help patients."

Abpro is currently in the developmental phase of its next-generation antibody therapies, focusing on HER2+ cancer treatments, including breast, gastric and colorectal cancers, in addition to treatments for Wet AMD/DME and COVID-19. These antibodies are developed using Abpro’s proprietary DiversImmune platform. Last year, Abpro partnered with Celltrion, which is a leading South Korean pharmaceutical company, in an exclusive collaboration to further advance ABP 102, a t-cell engager, which is being developed for the treatment of HER2+ breast, gastric and pancreatic cancer. In connection with that transaction, Abpro received an equity investment from Celltrion and is eligible for potential milestones up to $1.75 billion.

"We believe that Abpro has great potential to improve the lives of those suffering from life altering diseases with its immunotherapies," said Shahraab Ahmad, CEO of Atlantic Coastal. "I look forward to working closely with Ian Chan and the entire team at Abpro to advance their antibody treatments."

Brookline Capital Markets, a Division of Arcadia Securities, LLC, acted as a financial advisor to Abpro Corporation.

On September 21, 2023 Race Oncology Ltd (ASX:RAC) reported preclinical findings on the anti-cancer efficacy of bisantrene, which demonstrate its potential in enhancing the cancer-killing activity of the widely used drug doxorubicin across a diverse range of 143 human cancer cell lines (Press release, Race Oncology, SEP 21, 2023, View Source [SID1234635388]).

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Potent, broad anti-cancer activity
In a recently conducted preclinical study performed under contract at Oncolines in the Netherlands, bisantrene showcased potent anti-cancer activity against 113 of the 143 human cancer cell lines tested.

The cell lines represent 15 distinct types of cancer, including both blood and solid organ tumours.

Notably, the drug also significantly enhanced the efficacy of doxorubicin, one of the most used anthracycline chemotherapeutics in cancer treatment.

Key study highlights:

Bisantrene killed more than 79% of the cancer cell lines at a concentration below 500 nanometres (nM). Previous studies indicate that patient-tolerable doses achieve drug concentrations exceeding 3,000 nM in the blood, emphasising the clinical relevance of bisantrene’s potency.
When combined with doxorubicin, Bisantrene increased cell-killing activity in 86% of the tumour cells relative to doxorubicin alone.
Augments existing data
The study further augments Race Oncology’s existing data, which already showed that bisantrene enhances the efficacy of doxorubicin and cyclophosphamide in breast cancer cells and offers protection against anthracycline-induced cardiac damage in mice.

The study suggests that bisantrene holds broader clinical utility beyond treating breast cancer and acute myeloid leukaemia (AML).

Further clinical and preclinical studies could substantively expand its commercial and clinical value across various cancer types. The Race team and advisors are actively considering the best avenues to capitalise on this promising development.

On September 21, 2023, Seelos Therapeutics, Inc. (the "Company") reported to have entered into a securities purchase agreement (the "Securities Purchase Agreement") with certain purchasers identified on the signature pages thereto (the "Purchasers"), pursuant to which the Company agreed to issue and sell 15,000,000 shares (the "Shares") of its common stock, par value $0.001 per share (the "Common Stock") and accompanying common stock warrants to purchase up to 10,010,010 shares of Common Stock (the "Warrants") in a registered direct offering (the "Offering") (Filing, 8-K, Apricus Biosciences, SEP 21, 2023, View Source [SID1234635374]). The Shares and the Warrants were offered by the Company pursuant to its shelf registration statement on Form S-3 (File No. 333-251356) filed with the Securities and Exchange Commission (the "Commission") on December 15, 2020, as amended by Amendment No. 1 thereto filed with the Commission on December 22, 2020 and declared effective on December 23, 2020 (as amended, the "Registration Statement").

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The exercise price of the Warrants is $0.325 per share, subject to adjustment as provided therein, and the Warrants will be immediately exercisable upon issuance and will expire on the date that is five years following the original issuance date. In addition, the Warrants contain an alternative "cashless exercise" provision whereby a Warrant may be exchanged cashlessly for shares of Common Stock at the rate of 0.999 of a share of Common Stock per full share otherwise issuable upon a cash exercise. Each holder of a Warrant will not have the right to exercise any portion of its Warrant if the holder, together with its affiliates, would beneficially own in excess of 4.99% of the number of shares of Common Stock outstanding immediately after giving effect to such exercise (the "Warrant Beneficial Ownership Limitation"); provided, however, that upon 61 days’ prior notice to the Company, the holder may increase the Warrant Beneficial Ownership Limitation, but not to above 9.99%. The exercise price and number of shares of Common Stock issuable upon the exercise of the Warrants will be subject to adjustment in the event of any stock dividend, stock split, reverse stock split, recapitalization, reorganization or similar transaction, as described in the Warrants. If a registration statement covering the issuance of the shares of Common Stock issuable upon exercise of the Warrants is not available for the issuance, then the holders may exercise the Warrants by means of a "cashless exercise."

The Warrants are not and will not be listed for trading on any national securities exchange or other nationally recognized trading system.

The combined purchase price for one Share and accompanying Warrants to purchase shares of Common Stock for each Share purchased was $0.30. The closing of the Offering occurred on September 25, 2023. The Company expects the aggregate net proceeds from the Offering, after deducting the fees payable to financial advisors and other estimated offering expenses, to be approximately $4.0 million. The Company intends to use the aggregate net proceeds (excluding proceeds from any Warrant exercises) to repay $0.7 million of principal and accrued interest under that certain Convertible Promissory Note No. 1 issued to Lind Global Asset Management V, LLC ("Lind") on November 23, 2021, as amended on December 10, 2021, February 8, 2023 and May 19, 2023 (as so amended, the "Note") as required by the Letter Agreement (as defined below) and the remainder for general corporate purposes and to advance the development of its product candidates. The Company may also use the net proceeds from the Offering to make periodic principal and interest payments under, or to repay a portion of, the Note.

The Securities Purchase Agreement contains customary representations, warranties and agreements by the Company and customary conditions to closing. Under the Securities Purchase Agreement, the Company and each of its directors and executive officers has agreed, subject to certain exceptions, not to enter into any agreement to issue or announce the issuance or proposed issuance of any Common Stock or Common Stock equivalents for a period of 45 days following the closing of the Offering. The Company also agreed that until the six (6) month anniversary of the closing of the Offering (the "Closing Date"), the Company will not effect or enter into an agreement to effect any issuance of shares of Common Stock or Common Stock equivalents involving an at-the-market offering or variable rate transaction.

The foregoing summaries of the Securities Purchase Agreement and the Warrants do not purport to be complete and are qualified in their entirety by reference to the full texts of the form of Securities Purchase Agreement and the form of Warrant that are filed herewith as Exhibits 10.1 and 4.1, respectively.

The representations, warranties and covenants contained in the Securities Purchase Agreement and the Warrants were made only for purposes of such agreements and as of specific dates, were solely for the benefit of the parties to the Securities Purchase Agreement and the Warrants, respectively, and may be subject to limitations agreed upon by the contracting parties. Accordingly, the Securities Purchase Agreement and the Warrants are incorporated herein by reference only to provide investors with information regarding the terms of the Securities Purchase Agreement and the Warrants, and not to provide investors with any other factual information regarding the Company or its business, and should be read in conjunction with the disclosures in the Company’s periodic reports and other filings with the Commission.

The legal opinion, including the related consent, of Brownstein Hyatt Farber Schreck, LLP relating to the issuance and sale of the Shares and the shares of Common Stock underlying the Warrants is filed as Exhibit 5.1 hereto. The legal opinion, including the related consent, of Paul Hastings LLP relating to the issuance and sale of the Warrants is filed as Exhibit 5.2 hereto.

This report does not constitute an offer to sell, or the solicitation of an offer to buy, 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.

On September 21, 2023, and concurrently with the execution of the Securities Purchase Agreement, the Company entered into a letter agreement with Lind related to the Note (the "Letter Agreement"), pursuant to which the Company and Lind agreed that, in lieu of, and in full satisfaction of, both the monthly payment that would otherwise be due under the Note on September 23, 2023 and the interest payment that would otherwise be due on September 29, 2023, (i) the Company shall, by no later than September 29, 2023, pay to Lind cash in an aggregate amount equal to $686,564 and (ii) Lind shall have the right, at any time and from time to time, between the Closing Date and the date that is 45 days after the Closing Date, to convert the remaining amount of the monthly payment that would have otherwise been due on September 24, 2023 in the aggregate amount of up to $400,000 into shares of Common Stock at the lower of (a) the then-current Conversion Price (as defined in the Note, which is currently $6.00 per share) and (b) 85% of the average of the five (5) lowest daily volume-weighted average price during the twenty (20) trading days prior to the delivery by Lind of the applicable conversion notice.

Pursuant to the Letter Agreement, Lind further agreed that (a) the payment date for the monthly payment under the Note that would otherwise be due on October 23, 2023, and (b) the interest payment date for the interest payment under the Note that would otherwise be due on October 31, 2023, shall be the date that is 45 days following the Closing Date.

The foregoing summary of the Letter Agreement does not purport to be complete and is qualified in its entirety by reference to the copy of the Letter Agreement filed herewith as Exhibit 10.2 and incorporated herein by reference.

On September 21, 2023 Biocept, Inc. (Nasdaq: BIOC), a leading provider of molecular diagnostic assays, products and services, reported the full enrollment of 40 subjects with breast or non-small cell lung cancer (NSCLC) who have suspicious or confirmed leptomeningeal metastases (LM) in the feasibility phase of its prospective FORESEE clinical trial (NCT0414123) (Press release, Biocept, SEP 21, 2023, View Source [SID1234635329]). This trial is evaluating the performance of Biocept’s proprietary CNSide assay in monitoring the response to therapy of LM, a cancer in the membranes that surround the brain and spinal cord, and assessing its impact on treatment decisions made by physicians.

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"Early adoption and reorder rates are encouraging and suggest that neuro-oncologists are finding the information generated by CNSide as useful in managing patients with this devastating cancer."

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"Completing enrollment in this first phase of our FORESEE trial, and doing so ahead of our internal timeline, is significant as we work toward establishing CNSide as standard of care under the National Comprehensive Cancer Network, or NCCN, guidelines," said Antonino Morales, Biocept President and CEO. "We believe obtaining standard-of-care status is the best path forward to support further physician adoption and to set reimbursement at a rate that reflects the value of our test in the clinical decision making process. The FORESEE trial is specifically designed to measure the impact of CNSide on physicians’ clinical decisions to generate the data needed to help us reach this goal.

"Our CNSide assay is the first commercially available method that has the potential to objectively measure the presence of tumor in the central nervous system (CNS), as well as help guide and monitor therapy, an area of critical need for these terminally ill patients," he added. "Early adoption and reorder rates are encouraging and suggest that neuro-oncologists are finding the information generated by CNSide as useful in managing patients with this devastating cancer."

FORESEE is a two-part prospective clinical trial designed to follow subjects and collect data from each enrollee at four key time points in their treatment, as well as to compare CNSide cell detection in the cerebrospinal fluid to that of conventional cytology. CNSide has notable advantages over current standards of care, such as cytology, clinical evaluation and MRI, which have limited sensitivity and specificity. In retrospective pilot studies, CNSide demonstrated 92% sensitivity and 95% specificity in detecting LM. Additionally, CNSide is both qualitative and quantitative, which are key to monitoring treatment response and improving the ability of physicians to make or change treatment decisions.

"The current standards of care can present a significant obstacle in patient care due to the limitations in the detection and monitoring of LM. In addition to the current methods, there is a need for a reliable tool to diagnose and to monitor response to treatments in patients with LM," said Jonathan Yang, MD, PhD at the University of Washington and principal investigator at this site of the FORESEE trial. "In my practice I’ve found that CNSide provides important information that augments the detection and monitoring of LM, which is becoming increasingly important as patients with LM are living longer with improved quality of life due to improvement in treatments."

Biocept expects to have results from the feasibility phase of the FORESEE trial in the first half of 2024 and to then begin enrolling between 40 and 100 subjects in the trial’s validation phase. Enrollment is currently open at four clinical sites with two additional sites expected to join the FORESEE trial in the near term.

About CNSide

CNSide is a laboratory developed test (LDT) based on Biocept’s proprietary quantitative tumor cell capture and detection method, paired with assays to identify actionable molecular treatment targets. Given the genetic changes that can occur as metastatic cancer spreads to the CNS, the evaluation of cerebrospinal fluid with CNSide provides a unique opportunity to identify biomarkers in patients with metastatic carcinoma or melanoma to help guide physicians in therapy selection. In addition, the quantitative tumor cell count assay can be used in a serial fashion to monitor the response to therapy more effectively than other current methods.