On July 16, 2024 Clarity Pharmaceuticals (ASX: CU6) ("Clarity", "the Company"), a clinical stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported that it has entered into a supply agreement with TerraPower for Ac-225 for Clarity’s 225Ac-bisPSMA program (Press release, Clarity Pharmaceuticals, JUL 16, 2024, View Source [SID1234644867]).

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Clarity’s Executive Chairperson, Dr Alan Taylor, commented, "We are very excited to explore the benefits of our proprietary optimised dual-targeted PSMA product in our first TAT program utilising TerraPower-supplied Ac-225. We have the right team to develop and later commercialise a best-in-class TAT product to complement the treatment paradigm, particularly in later-stage prostate cancer patients, and overcome the hurdles seen with other PSMA-based targeting agents.

"Manufacturing of Ac-225 poses a number of challenges at this time, including access for clinical studies, purity of isotope and scalability to meet requirements for a commercial launch. The Ac-225 from TerraPower fits into our strategy of developing sustainable, scalable and environmentally preferred solutions to radionuclide sourcing at a purity level appropriate for clinical practice and made directly in the United States. This avoids having to supply Ac-225 from Russia and use sources containing significant Ac-227 contamination, a radionuclide more radiotoxic than plutonium. A number of other isotope manufacturers are now developing potentially scalable commercial processes, including our existing partner for copper-67 supply, NorthStar Medical Isotopes LLC, and we will look to continue adding Ac-225 suppliers to our network. As such, with increasing focus on the Ac-225 supply chain, the probability of successfully developing and commercialising these treatments has grown from a supply perspective.

"The new beta-particle therapies, such as Cu-67 and Lu-177, with their favourable energy characteristics and path lengths, are revolutionising the radiopharmaceutical space because of their proven efficacy and excellent safety profiles compared to many other beta and alpha emitting isotopes. The small number of commercially available targeted radiopharmaceutical therapies all use beta emitting isotopes, and they represent the best opportunity to significantly change the treatment paradigm with the potential for much earlier stage treatments and in combination with standard of care treatments or immuno-oncology products. Novartis, the current leader in radiopharmaceuticals, has cornered much of the Lu-177 supply market, given the precarious supply chain of Lu-177 and reliance on a limited number of aging nuclear reactors, inhibiting new companies from entering this space1. Clarity’s unique proprietary position of having a cage that holds copper isotopes and exclusive supply of Cu-67, which is sourced from scalable electron accelerators as opposed to the small and aging fleet of nuclear reactors, means that Clarity is well positioned to drive a global shift in the treatment paradigm for cancer sufferers. As such, beta-particle therapy with Targeted Copper Theranostics (TCTs) remains Clarity’s key focus.

"Clarity’s bisPSMA program could be the game-changer in prostate cancer therapy given the increased uptake and retention in tumours enabled by the dual-targeting molecule and with impressive preclinical and clinical data generated to date. By combining our optimised bisPSMA with Ac-225, we have the opportunity to complement our beta-particle therapy product, 67Cu-SAR-bisPSMA. Developing both alpha- and beta-emitting therapy products for prostate cancer puts Clarity in a unique position to offer powerful treatment approaches to improve outcomes for these patients as using each product at different stages of the disease would provide more options to the patients.

"Our 225Ac-bisPSMA preclinical research program has been underway for some months with investigations to date focused on identifying a lead compound from a number of different analogues through measuring biodistribution, tumour uptake, radiolabelling efficiency and product stability as we move closer to clinical development with an optimised PSMA agent utilising Ac-225.

"By integrating TAT into our existing advanced TCT programs, Clarity is positioning itself to fundamentally transform the arsenal of treatments available for oncologists and their patients. This strategic move allows us to broaden our deep pipeline of clinical and pre-clinical assets and make significant progress towards our ultimate goal of better treating adults and children with cancer."

The Supply Agreement is effective July 2024. Supply under this agreement is expected to commence in November 2024, while supply before November 2024 will be carried out under the existing Limited Product Supply and Evaluation Agreement. The supply agreement is for an initial period of 2 years and can be extended under the terms of the contract. Cancellation provisions are at industry standard rates.

On July 15, 2024, Pulse Biosciences, Inc. (the "Company") reported to have entered into an equity distribution agreement (the "Distribution Agreement") with Canaccord Genuity LLC and Needham & Company, LLC (each a "Sales Agent" and together, the "Sales Agents"), as sales agents, pursuant to which the Company may offer and sell, from time to time, through the Sales Agents, shares of the Company’s common stock, par value $0.001 per share (the "Common Stock"), having an aggregate offering price of up to $60.0 million (the "Shares") (Filing, Pulse Biosciences, JUL 15, 2024, View Source [SID1234644892]).

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The Company is not obligated to sell any Shares under the Distribution Agreement. Subject to the terms and conditions of the Distribution Agreement, the Sales Agents will use commercially reasonable efforts, consistent with their normal trading and sales practices, to sell Shares from time to time based upon the Company’s instructions, including any price, time or size limits or other customary parameters or conditions specified by the Company. Under the Distribution Agreement, the Sales Agents may sell Shares in transactions that are deemed to be "at the market" offerings as defined in Rule 415(a)(4) under the Securities Act of 1933, as amended (the "Securities Act"), including sales made by means of ordinary brokers’ transactions, including directly on the Nasdaq Capital Market or into any other existing trading market for the Shares, or sales made to or through a market maker, in block transactions or by any other method permitted by law, including negotiated transactions. Sales may be made at market prices prevailing at the time of a sale or at prices related to prevailing market prices or at negotiated prices. The Company will pay the Sales Agents a commission of up to 3.0% of the gross sales price per share sold by the Sales Agents. The Company also will reimburse the Sales Agents for certain specified expenses in connection with entering into the Distribution Agreement. The Company has no obligation to sell any of the Shares under the Distribution Agreement and may at any time suspend solicitations and offers under the Distribution Agreement.

The issuance and sale, if any, of the Shares by the Company under the Distribution Agreement will be made pursuant to the Company’s effective registration statement on Form S-3 (File No. 333-278322) filed with the U.S. Securities and Exchange Commission (the "SEC") on March 28, 2024, and declared effective as of April 8, 2024, as well as a related registration statement on Form S-3 (File No. 333-280805), filed with the SEC on July 15, 2024 pursuant to Rule 462(b) of the Securities Act, which became effective immediately upon filing. The Company filed a prospectus supplement with the SEC on July 15, 2024 in connection with the offer and sale of the Shares pursuant to the Distribution Agreement.

The foregoing description of the Distribution Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Distribution Agreement, a copy of which is filed as Exhibit 1.1 to this Current Report on Form 8-K and is incorporated herein by reference. The legal opinion of Baker & Hostetler LLP, counsel to the Company, relating to the validity of the issuance and sale of the Shares being offered pursuant to the Distribution Agreement, is filed as Exhibit 5.1 to this Current Report on Form 8-K and is incorporated herein by reference.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy any Shares under the Distribution Agreement nor shall there be any sale of such Shares in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

On July 15, 2024 Diakonos Oncology Corporation ("Diakonos"), a clinical stage immuno-oncology company, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the company’s unique dendritic cell vaccine (DCV) for pancreatic ductal adenocarcinoma (Press release, Diakonos Oncology, JUL 15, 2024, View Source [SID1234644881]). In addition, the company has named to its Scientific Advisory Board, Daniel D. Von Hoff, M.D., Distinguished Professor at the Translational Genomics Research Institute (TGen) in Phoenix, AZ, and City of Hope, and an experienced investigator against pancreatic cancer.

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"This second FDA Fast Track designation of our autologous dendritic cell vaccines for pancreatic cancer is another acknowledgement of the incredible potential of this innovative immunotherapy for treating the most deadly cancers," said Mike Wicks, Diakonos CEO. "We are thrilled to have Dr. Von Hoff join us as an advisor as we pursue clinical development of our vaccine in this deadly disease," Mr. Wicks added. "The first designation was for our lead vaccine for glioblastoma multiforme (GBM) which successfully completed dosing for the Phase 1 trial and has significantly improved 12 month survival in those patients to well over what would be expected with the standard of care." (See the press release)

Dr. Von Hoff is an internationally recognized physician and scientist whose research has contributed to the development of many anticancer agents that are routinely used in clinical practice. His research at TGEN focuses on development of therapies for patients with advanced pancreatic cancer. He also was a founder of ILEX Oncology which was acquired by Genzyme.

In addition to his work with TGEN, Dr. Von Hoff holds the Virginia G. Piper Distinguished Chair for Innovative Cancer Research at HonorHealth Clinical Research Institute, and is Professor of Medicine at the Mayo Clinic, Scottsdale, AZ.

"Diakonos’s unique dendritic cell vaccine has shown encouraging results in treating glioblastoma, a terrible disease with few effective treatments. Pancreatic cancer patients also need additional treatment options," said Dr. Von Hoff. "I look forward to working with Diakonos to help develop effective treatments for patients with pancreatic cancer with the same targeted technology."

About FDA Fast Track:

FDA Fast Track designation is intended to speed development and review of drugs that show early clinical promise in treating severe or life-threatening conditions. Pancreatic ductal adenocarcinoma is the most common pancreatic cancer. It is the third leading cause of cancer deaths in the U.S. and the number of cases is growing. According to the National Institutes of Health, the average five-year survival rate is less than 13%, and in 2024 an estimated 51,750 people will die and 66,440 will be newly diagnosed.

About Diakonos’ DCV Technology:

The company’s DCVs are made with a patient’s dendritic cells and a sample of their tumor. These highly differentiated double-loaded dendritic cell vaccines activate robust cytotoxic TH1 cell signaling pathways that initiate a natural immune response to target and eliminate cancer cells. This is achieved without any genetic modification of the patient’s immune cells, which greatly simplifies the manufacturing process and significantly reduces costs when compared to leading cell therapy approaches.

On July 15, 2024 Integrated DNA Technologies (IDT), a global leader in CRISPR genome editing solutions, reported a licensing agreement with SeQure Dx, a company focused on off-target analysis for preclinical and clinical gene modification customers, bolstering IDT’s complete CRISPR portfolio comprised of world-class RUO to CGMP solutions from design to analysis (Press release, INTEGRATED DNA TECHNOLOGIES, JUL 15, 2024, View Source [SID1234644880]). The licensing agreement enables IDT to support cell and gene therapy developers through all phases of their CRISPR-based therapeutic programs by providing comprehensive off-target analysis services, powered by SeQure Dx’s GUIDE-seq technology, alongside IDT’s award-winning rhAmpSeq CRISPR Analysis System.

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"Off-target effects continue to be a primary concern in genome editing and are still not fully understood," said Sandy Ottensmann, VP/General Manager, Gene Writing & Editing Business Unit at IDT. "With an increasing pipeline of CRISPR-based therapeutics that are entering and progressing in trials, the delivery of safer and more efficient genome editing platforms to the clinic becomes paramount. IDT’s expanded off-target analysis capabilities demonstrate a transformational shift we are making to support cell and gene therapy developers in their transition to the clinic, in a drive to make life-changing therapies as safe as possible."

Dr. Keith Joung, Scientific Founder of SeQure Dx, added, "SeQure’s best-in-class off-target nomination and confirmation platforms will seamlessly complement IDT’s CRISPR-based portfolio of products and services. By combining SeQure’s & IDT’s innovative technologies, this will enhance precision and safety in gene editing, bringing transformative solutions to researchers and patients worldwide."

The licensing agreement with SeQure Dx expands IDT’s comprehensive off-target analysis capabilities by providing the company access to SeQure Dx’s next generation sequencing-based gene editing off-target analysis technology, GUIDE-seq. Originally developed by Keith Joung’s group at Massachusetts General Hospital, GUIDE-seq is a widely used off-target nomination assay, making it an excellent starting point for developing and evaluating CRISPR-focused therapeutics. Broadly used by academic researchers, biotechs, large pharma and biopharma companies to help characterize potential off-target events in their genome editing results, GUIDE-seq provides genome-wide, unbiased identification of double-stranded breaks by sequencing. It has contributed in part to the successful development and release of multiple therapeutics.

IDT’s CRISPR Innovation Journey

Last year, to help address development and manufacturing challenges in a capacity-constrained market for CGMP/Q7 services, IDT opened a therapeutic oligonucleotide manufacturing facility in the U.S. to support the increased demand for high-quality cell and gene therapy components. These critical reagents are foundational to delivering on the promise of therapies to patients and are key to accelerating the path to clinic for developers.

With IDT’s proprietary rhAmpSeq CRISPR Analysis System, regulatory expertise, RUO to CGMP manufacturing capabilities, and dedicated support team, customers can expect differentiated off-target analysis services from a single provider for their CRISPR therapeutic development. Launched in 2021, IDT’s rhAmpSeq CRISPR Analysis System is an end-to-end solution for characterizing and quantifying the full array of on- and off-target genome editing events in CRISPR research products. The novel tool, endorsed by renowned scientists, continues to grow in popularity as an assay for off-target confirmation, and enables the robust analysis of resulting next generation sequencing data. For more information about IDT’s comprehensive off-target analysis services and capabilities, visit https://go.idtdna.com/OTE-analysis-request-consult.

On July 15, 2024 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported that data published in the journal Cell demonstrate that neoadjuvant monotherapy with the poly (ADP-ribose) polymerase (PARP) inhibitor niraparib results in a high response rate and reshapes the tumor microenvironment (TME), providing new targets for immunotherapy and combination regimens in patients with homologous recombination deficiency (HRD) positive ovarian cancer (Press release, Zai Laboratory, JUL 15, 2024, View Source [SID1234644879]). The study revealed niraparib preferentially suppresses certain immune cells that support the growth of HRD-positive ovarian tumors.

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This Zai Lab-supported study also showed that targeted clearance of infiltrating regulatory T cells (eTregs) using Zai Lab’s investigational CCR8 antibody, ZL-1218, significantly sensitized niraparib against HRD tumors, resulting in decreased tumor burden in pre-clinical models.

"Given the prevalence of HRD in cancer and its role in rendering tumors vulnerable to PARP inhibition, this study fills the knowledge gap regarding the impact of HRD and related therapies on the tumor microenvironment," said Professor Qinglei Gao, Chief of Gynecologic Oncology Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. "By decoding the tumor-reactive T cells in the HRD-positive TME that are regulated by eTregs, these findings have profound implications for future oncology research and therapeutic development for HRD-positive ovarian cancer and other HRD-related cancers."

To investigate the effects of HRD, neoadjuvant therapies, and their interactions on the TME, investigators utilized tumor tissues from a clinical study (NCT04507841) evaluating niraparib for the neoadjuvant treatment of unresectable ovarian cancer. In parallel, tissue samples from patients receiving neoadjuvant chemotherapy (NACT) were also collected.

Profiling of these samples yielded valuable data delineating the divergence in TME between HRD-positive vs. homologous recombination-proficient (HRP) tumors, as well as their respective phenotypic evolution following the introduction of neoadjuvant therapies.

Key findings of the study included:

Patients receiving neoadjuvant monotherapy with niraparib achieved 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively.
Overall, the safety profile of NANT was manageable, and no new safety signal was observed, with hematologic toxicities as the most common treatment-related adverse events.
The results indicate that NANT is an effective neoadjuvant treatment option for controlling disease progression in patients with HRD-positive high-grade serous ovarian cancer (HGSOC).
eTregs were identified as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells.
The addition of the CCR8 antibody, ZL-1218, to niraparib showed a significantly pronounced inhibitory effect on eTregs in pre-clinical models, suppressing tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.
"Zai Lab is pleased to support this important translational research which breaks new ground in our understanding of the tumor microenvironment in HRD-positive ovarian cancer," said Rafael G. Amado, M.D., President, Head of Global Research and Development, Zai Lab. "By identifying new immunotherapeutic targets in the TME, these findings could bolster efforts to improve outcomes for patients with HRD+ tumors."