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.

On September 21, 2023 JURA Bio, a biotechnology company developing immune-based therapeutics using machine learning and synthetic biology, reported a research collaboration with Syena, a cell therapy product company and subsidiary of Replay, a genome writing company, to develop T cell receptor (TCR) based therapies (Press release, JURA Bio, SEP 21, 2023, View Source [SID1234635328]).

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"We’re thrilled to announce our first partnership with Replay and its product company Syena. This partnership validates our approach of using synthesized human T cell repertoires to generate safe and effective libraries to discover antigen specific TCRs at scale," said Elizabeth Wood, Ph.D., Founder & CEO, JURA Bio. "The human immune system is a powerful source of safe and effective immune receptors, and while one patient might lack a TCR necessary to fight cancer, it may be present in another. By leveraging machine learning to rewrite the gene synthesis process from the ground up, we can produce extraordinarily high-quality immune receptors libraries to discover and train probabilistic machine learning models to ensure a faster development process that identifies TCRs recognizing the most challenging therapeutic targets."

"JURA Bio’s highly differentiated TCR discovery platform has transformative potential and combines the power of synthetic biology with that of machine learning. We look forward to working with them to identify high performing TCRs recognizing challenging but therapeutically important targets such as KRAS G12D," said Adrian Woolfson, Executive Chairman, President, and Co-Founder of Replay. "JURA Bio’s unique AI tools and expertise in synthetic libraries offers a differentiated approach for discovering TCRs. This will be invaluable in helping Replay’s cell therapy product company Syena to advance novel TCR-NK therapies into the clinic."

Lachlan MacKinnon, CEO and Co-Founder of Replay, said: "We are delighted to be partnering with JURA Bio, and their innovative team of synthetic and computational biologists to develop highly differentiated TCR-NK cell therapies. This new partnership is an exciting opportunity for Replay’s cell therapy product company Syena to leverage JURA Bio’s powerful toolkit of machine learning and synthetic protein design coupled with their extensive expertise and to use this to advance the development of our engineered TCR-NK cell therapy programs."

JURA Bio will receive an upfront payment as well as research funding for the period of the partnership. The details of the financial terms of the agreement were not disclosed. If the option is exercised, Replay and its cell therapy product company Syena will be responsible for global development and hold exclusive worldwide commercialization rights on all TCR-NK therapies resulting from the partnership. JURA Bio will be eligible to receive development, regulatory, and commercial milestone payments in addition to tiered deferred option payments on global net sales for products based on TCRs arising from the collaboration, as well as royalties on products utilizing at least one of the licensed technologies.

Replay launched Syena, an oncology-focused product company, with The University of Texas MD Anderson Cancer Center in February 2023. The engineered TCR-NK technology in Syena is based on the scientific discoveries of Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation & Cellular Therapy at MD Anderson.

"In areas where conventional methods are insufficient, machine learning emerges as the catalyst that unlocks the full potential of cell-based therapy and personalized medicine," said Julie Norville, Founder and Chief Technical Officer, JURA Bio. "We founded the company in 2017 as a synthetic biology and probabilistic machine learning entity. Our team has built all the tools necessary to define machine-learning driven candidates at an incredible scale, and has been able to test and develop these with incredible speed. We look forward to working with Replay and its cell therapy product company Syena to develop new treatments to address cancers with high unmet medical need."

In addition to the partnership with Replay and Syena, JURA Bio also announced a $16.1M financing led by Michael Chambers, John Ballantyne, Fontus Capital, and Josh Elkington. The funding will accelerate the mapping of the adaptive immune system. JURA Bio’s aims to complete a predictive map of TCR-antigen-HLA binding powered by an off-the-shelf library of >100B synthesized human T cells and their cognate antigens and HLAs by the end of 2024. It will during this timeframe also expand its machine-learning based gene synthesis into the design and discovery of B cell receptors.

Most existing generative machine learning workflows face a fundamental bottleneck in their ability to synthesize and test their candidates of choice. JURA has built an ML-first workflow that incorporates the relevant underlying chemistry, physics, and biology, as well as developing a statistical framework for evaluating model quality that allows them to build and train flexible and reliable models from huge amounts of data. JURA Bio is able to propose, build, and physically assay candidates at a scale previously unimaginable.

JURA Bio’s ML-improved gene synthesis technology has generated an off-the-shelf library of 100 billion potential human and improved TCR candidates that are ready for antigen-specific TCR discovery and development. The company has already discovered high-value TCRs for prostate cancer and other key neoantigen targets that have never been before recorded in key HLA-types.

In another example, JURA has generated a polyclonal candidate pool for six melanoma patients that were refractory to MART-1 specific adoptive cell therapy. Six refractory melanoma patients failed to respond to adoptive transfer of autologous cells from healthy donors. Using an off-the-shelf HLA-matched variational synthesis library of TCR candidates, JURA Bio identified 10 candidates for expansion and engineering to create a truly personalized therapeutic polyclonal candidate pool for each individual. The company has also manufactured peptidome and virodome-scale libraries of antigens to help determine the underlying mechanisms of autoimmunity.

"It is remarkable how little we know about the cell identities underlying and driving autoimmune disease. We are not able to reliably say how many are restricted to specific individuals or shared by common mechanisms population-wide. In having the ability to screen at the scale of human peptidomes, we will not only learn a lot about potential therapeutics, but also better understand the underlying heterogeneity of autoimmune disease," said Everett Meyer, Associate Professor of Medicine, Blood and Marrow Transplantation and Cellular Therapy, Director Stanford Cellular Immune Tolerance Program.

"AI-ML and multiplex libraries are useful tools individually, but when combined together they can generate remarkable synergy, known as ML-ML variational synthesis. This has the potential to generate billions to trillions-fold of potential candidates. The mastery of this strategy for TCR, MHC, and T-cell engineering at JURA is without competition and in huge demand," said George Church, Ph.D., Founder & Scientific Advisory Board Chair, JURA Bio.

Additional members of JURA Bio’s scientific advisory board include Debora Marks, PhD (Harvard), David Hafler, MD (Yale), Jay Fishman, MD (Harvard/MGH), Melina Fan, PhD (Addgene), Kevan Herold (Yale), Lester Mackey (Microsoft Research/Stanford), and Everett Meyer, MD/PhD (Stanford).

On September 21, 2023 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to alisertib, a selective, small-molecule, orally administered inhibitor of aurora kinase A, for the treatment of patients with small cell lung cancer (SCLC) (Press release, Puma Biotechnology, SEP 21, 2023, View Source [SID1234635327]). SCLC is an aggressive form of lung cancer with a poor prognosis, and with limited treatment options for patients whose cancer has progressed on or after platinum-based chemotherapy.

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"Obtaining Orphan Drug Designation from the FDA signifies our continued progress and commitment to the development of alisertib for the treatment of small cell lung cancer," said Alan H. Auerbach, Chief Executive Officer, President and Founder of Puma. "There is an urgent need for new treatments for patients with small cell lung cancer, and we look forward to the initiation of our Phase II trial (Study PUMA-ALI-4201) of alisertib in small cell lung cancer."

The FDA grants Orphan Drug Designation to investigational therapies being developed to treat, diagnose or prevent a rare disease or condition affecting fewer than 200,000 people in the United States. Further, Orphan Drug Designation provides benefits to drug developers, including assistance in the drug development process, tax credits for qualified trials, waiver of certain FDA fees, and the potential for seven years of post-approval marketing exclusivity.

Puma received FDA clearance of its Investigational New Drug application for the clinical development of alisertib monotherapy for the treatment of patients with extensive stage SCLC in August 2023 and anticipates initiating the Phase II trial in the second half of 2023.