On January 25, 2024 Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through the development of best-in-class IL-2 therapeutics, reported dosing of the first patient in the initial Phase 2 expansion cohorts of its Phase 1/2 clinical trial evaluating AU-007 for treatment of unresectable locally advanced or metastatic cancers (Press release, Aulos Bioscience, JAN 25, 2024, View Source [SID1234639471]). AU-007 is a human IgG1 monoclonal antibody designed to harness the power of interleukin-2 (IL-2) to eradicate solid tumors, and the first AI-designed human monoclonal antibody to be tested in a clinical trial. Phase 1 data demonstrate that AU-007 is currently the only IL-2 agent that can reduce regulatory T cells (Tregs), which suppress the immune system.

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"Dosing of the first patient in the Phase 2 portion of our AU-007 Phase 1/2 study marks a significant milestone as we advance development of this promising, novel IL-2 therapeutic for the treatment of solid tumor cancers," said Aron Knickerbocker, Aulos Bioscience’s chief executive officer. "AU-007 was created to solve pressing safety and efficacy challenges associated with IL-2 therapeutics, and we are encouraged by ongoing new Phase 1 data that indicate clinical activity in several heavily pre-treated patients whose tumors progressed through checkpoint inhibitors. We are grateful to the participating patients and investigators in this clinical trial, and look forward to enrolling additional patients and presenting clinical data from the Phase 2 expansion cohorts later this year."

Aulos’ Phase 1/2 clinical trial is a two-part, open label, first-in-human study evaluating the safety, tolerability, immunogenicity and clinical activity of AU-007 in patients with unresectable locally advanced or metastatic cancer. The initial Phase 2 expansion cohorts focus on melanoma and renal cell carcinoma (RCC), with AU-007 administered every two weeks in combination with a single loading dose of low-dose, subcutaneous Proleukin (aldesleukin; recombinant human IL-2), or with AU-007 and low-dose, subcutaneous Proleukin, both administered every two weeks.

Created by Biolojic Design, AU-007’s unique computational design allows it to bind precisely to the portion of IL-2 that binds to CD25, which prevents IL-2 from binding to high-affinity IL-2 receptors on Tregs, vasculature, pulmonary tissue and eosinophils. This redirects IL-2 to medium-affinity receptors on effector T cells (Teffs) and natural killer (NK) cells, which expand and kill tumor cells. Phase 1 dose escalation cohort data presented at two separate medical meetings last fall demonstrate that when AU-007 is administered to patients as monotherapy or in combination with low doses of Proleukin, the number of immunosuppressive Tregs decreases and the numbers of Teffs and NK cells increase. Additionally, data indicate that AU-007 is well tolerated and tumor shrinkage was observed in patients with melanoma, bladder, kidney, head and neck, and lung cancers.

To learn more about the AU-007 clinical trial program, please visit ClinicalTrials.gov (identifier: NCT05267626). For patients and providers in the U.S., please visit www.solidtumorstudy.com. For patients and health professionals in Australia, please visit www.solidtumourstudy.com.

About AU-007
AU-007 is a computationally designed, human IgG1 monoclonal antibody that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 leverages IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by effector T cells, from binding to trimeric receptors on regulatory T cells while still allowing IL-2 to bind and expand effector T cells and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to CD25-containing receptors on eosinophils, as well as vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy.

On January 25, 2024 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer, reported the closing of its previously announced underwritten public offering of 32,379,667 shares of its common stock, which includes 5,325,000 shares sold and issued upon the exercise in full by the underwriters of their option to purchase additional shares of common stock, and, in lieu of common stock to certain investors, pre-funded warrants to purchase 8,445,333 shares of common stock (Press release, Adicet Bio, JAN 25, 2024, View Source [SID1234639488]). The shares of common stock were sold at a public offering price of $2.40 per share and the pre-funded warrants were sold at a public offering price of $2.3999 per pre-funded warrant, which represents the per share public offering price of each share of common stock minus the $0.0001 per share exercise price for each pre-funded warrant. The aggregate gross proceeds from the offering, before deducting underwriting discounts and commissions and offering expenses, were approximately $98.0 million. All of the securities in the offering were sold by Adicet.

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Jefferies and Guggenheim Securities acted as joint book-running managers for the offering. Truist Securities also acted as a joint bookrunner. Wedbush PacGrow and JMP Securities, A Citizens Company acted as co-managers.

The securities described above were offered by Adicet pursuant to a shelf registration statement that was previously filed with, and subsequently declared effective on May 9, 2022 by, the U.S. Securities and Exchange Commission ("SEC"). A final prospectus supplement and accompanying prospectus relating to and describing the terms of the offering was filed with the SEC on January 24, 2024. Copies of the final prospectus supplement and the accompanying prospectus relating to the offered securities may be obtained from Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, NY 10022, by telephone at (877) 821-7388, or by email at [email protected] or Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, NY 10017, by telephone at (212) 518-9544, or by email at [email protected].

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

On January 25, 2024 Genialis, the RNA-biomarker company, and Debiopharm, a privately-owned, Swiss-based biopharmaceutical company aiming to establish tomorrow’s standards of care to cure cancer and infectious diseases, reported to have reached an agreement to define and discover biomarkers within the DNA Damage Repair (DDR) biology space to predict the clinical benefit of one or more drugs in Debiopharm’s pipeline (Press release, Debiopharm, JAN 25, 2024, View Source [SID1234639473]). The initial phase kicked off this month, deploying Genialis’ biology-first, machine learning-enabled ResponderIDTM framework to develop predictive biomarkers for DDR-directed therapies.

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"Debiopharm continues to lead the oncology field in adopting artificial intelligence solutions at various stages across our preclinical and clinical development programs. Genialis’ expertise and cutting-edge technologies are an ideal fit to help us make the smartest translational decisions and advance our drugs to reach the right patients," said Bertrand Ducrey, CEO of Debiopharm.

Many cancers exhibit deficiencies in one or more DNA damage response pathways. Various classes of approved and investigational drugs aim to exploit known sensitivities; however, the heterogeneous biology of DNA damage response means that one drug only fits some, and combinations may prove essential. Biomarkers will help select patients whose cancer biologies are best suited to treatment with the right drug targeting the active disease mechanism.

"DNA damage response is among the most exciting biological domains of cancer drug development today and an area in which Debiopharm is working on several exciting molecules," said Carolina Haefliger, Head of Translational Medicine at Debiopharm. "Genialis’ biology-first approach allows us to collaborate in a truly scalable way, incorporating novel AI-based solutions in our programs."

Using biomarkers increases the odds of advancing an oncology clinical asset to the next trial phase by 5-12 fold[1]. However, post-approval, many of the best drugs achieve clinical benefit in only 30-40 percent of patients, and even those existing targeted therapies considered successful and supported by a biomarker can benefit from further refinement of patient tailoring strategies.

"Genialis’ RNA biomarkers have proved especially well-suited to support the development of new drugs targeting complex biological systems," said Mark Uhlik, Vice President of Biomarker Discovery at Genialis. "Debiopharm is working on some really promising molecules, and Genialis’ biomarkers will help ensure these drugs have the best possible chance of clinical success."

Genialis is based in Boston, Mass., and will attend PMWC in Santa Clara, Calif., from January 23-25, 2024. To request a meeting or for more information on ResponderID, please email [email protected] or visit www.genialis.com

Debiopharm is headquartered in Lausanne, Switzerland, and will be presenting at the 7th Annual DDR Inhibition Conference in Boston from January 29-30, 2024.

About DNA-Damage Repair (DDR)
When cells have damaged DNA, they need to undergo a repair process called DDR to be able to survive. Cancer cells use their hyperactive DDR response to divide and grow uncontrollably, which promotes cancer expansion. Inhibition of DDR, particularly in combination with other anticancer agents, induces an overall arrest in the uncontrollable cancer cell cycle. This ultimately activates a self-destruction program in cancer cells. DDR inhibitors are currently being tested in preclinical and clinical studies.

On January 25, 2024 Blue Earth Diagnostics, a Bracco company and recognized leader in the development and commercialization of innovative positron emission tomography (PET) radiopharmaceuticals, reported results from a sub-analysis of data from the Phase 3 SPOTLIGHT trial (NCT04186845) which investigated the use of POSLUMA (flotufolastat F 18) PET in suspected biochemical recurrence of prostate cancer (Press release, Blue Earth Diagnostics, JAN 25, 2024, View Source [SID1234639489]). The sub-analysis assessed the impact of POSLUMA on treatment plans for patients with recurrent prostate cancer after curative-intent primary therapy. POSLUMA (flotufolastat F 18) injection (formerly referred to as 18F-rhPSMA-7.3) is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level.

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Results highlights:

Flotufolastat F 18 PET imaging was positive for recurrent prostate cancer in 84% (81/97) of patients in the sub-analysis.
In 89% (86/97) of patients, management plans were changed following review of the flotufolastat F 18 PET scan results.
91% (78/86) of changes were considered major, defined as a change in the treatment modality.
75% (6/8) of patients whose plans were changed in favor of watchful waiting had a negative flotufolastat F 18 scan.
All patients with management plans that were revised from salvage therapy to non-curative systemic therapy had distant/extrapelvic flotufolastat F 18-avid lesions.
"Recurrent prostate cancer presents challenges, and the ability to determine the extent and location of recurrent disease to inform appropriate clinical management is key for physicians and their patients, as up to 40% of patients who undergo radical prostatectomy, and up to 50% of patients who undergo radiation therapy will develop local or distant recurrences within 10 years," said Przemyslaw Twardowski, MD, Saint John’s Cancer Institute at Providence Saint John’s Health Center, Santa Monica, Calif., on behalf of the SPOTLIGHT Study Group. "The SPOTLIGHT study investigated the diagnostic performance of POSLUMA PET imaging as a potential decision-making aid in assessing suspected biochemical recurrence of the disease. This sub-analysis further examined the impact of POSLUMA PET imaging on patients’ management plans. Results showed that POSLUMA identified recurrence sites in the majority of patients, frequently resulting in major changes to previously planned management plans. Patient treatment based on visualization of POSLUMA-avid lesions has the potential to facilitate optimal targeting of recurrence sites and help patients avoid futile salvage therapy."

"We are very pleased to present these results to the oncology community at ASCO (Free ASCO Whitepaper) GU," said David E. Gauden, D.Phil., Chief Executive Officer of Blue Earth Diagnostics. "POSLUMA represents a new class of high-affinity PSMA-targeted radiopharmaceuticals based on novel radiohybrid technology, and provides physicians with clinically useful information based on its performance at low PSA levels, PSMA binding and low urinary bladder activity. Our product has been added to nationally recognized clinical oncology guidelines for prostate cancer, alongside and for all the same categories as the other currently FDA-approved PSMA PET radiopharmaceuticals. POSLUMA is labeled with the radioisotope fluorine-18 (18F) to leverage high image quality and to enable broad, readily available geographic access for patients via the manufacturing and distribution network of our commercial U.S. manufacturer and distributor, PETNET Solutions Inc, A Siemens Healthineers Company."

The findings were discussed in a moderated poster presentation at the ASCO (Free ASCO Whitepaper) GU 2024 Genitourinary Cancers Symposium (ASCO GU) on January 25, 2024. "Impact of 18F-flotufolastat PET on management of patients with recurrent prostate cancer: Data from the SPOTLIGHT study," was presented by Przemyslaw Twardowski, MD, Saint John’s Cancer Institute at Providence Saint John’s Health Center, Santa Monica, Calif., on behalf of the SPOTLIGHT Study Group. Full session details are available in the ASCO (Free ASCO Whitepaper) GU online program here.

About the study

The sub-analysis of SPOTLIGHT data from the 389 patient study assessed the impact of flotufolastat F 18 on planned treatment after curative-intent primary therapy. The present analysis focused on patients who had a flotufolastat F 18 scan and sufficient data for management plan evaluation. Onsite investigators recorded patients’ management plans before and after flotufolastat F 18 PET. Plans were then categorized as "no change," "major change,"" other change," "additional information required" or "intended plan not valid." A "major change" was defined as a change in treatment modality (e.g., salvage radiation to systemic therapy), while "other change" represented a change within a modality (e.g., modified radiation therapy field). All imaging data were then submitted for blinded image evaluation by 3 central readers.

In total, 97 patients (median [range] PSA: 0.08 [0.09-134.6]] ng/mL) had an evaluable flotufolastat F 18 PET scan and sufficient data to evaluate management plan changes. Most patients, 86/97 (89%) had a change to their management plan post-scan. A "major change" was noted for 78 (80%) patients, while 8 (8.2%) had an "other change." Onsite imaging reads showed that both positive and negative flotufolastat F 18 scans influenced management planning. While 88% of revisions occurred after a positive scan, 75% of those whose management plans were revised to watchful waiting had negative scans. All patients with management plans revised from salvage therapy to non-curative systemic therapy had distant/extrapelvic flotufolastat F 18-avid lesions.
No serious adverse reactions were attributed to flotufolastat F 18 in the SPOTLIGHT study. Overall, 16/389 (4.1%) patients had at least one treatment-emergent adverse event that was considered possibly related/related to flotufolastat F 18. The most frequently reported events were: hypertension: 1.8% (n=7); diarrhea: 1.0% (n=4); injection site reaction: 0.5% (n=2), and headache: 0.5% (n=2).
About Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA)

Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA) compounds consist of a radiohybrid ("rh") Prostate-Specific Membrane Antigen-targeted receptor ligand which attaches to and is internalized by prostate cancer cells, and they may be radiolabeled with imaging isotopes for PET imaging, or with therapeutic isotopes for therapeutic use – providing the potential for creating a true theranostic technology. Radiohybrid technology and rhPSMA originated from the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive, worldwide rights to rhPSMA diagnostic imaging technology from Scintomics GmbH in 2018, and therapeutic rights in 2020, and sublicensed the therapeutic application to its sister company Blue Earth Therapeutics. Blue Earth Diagnostics received U.S. Food and Drug Administration approval for its radiohybrid PET diagnostic imaging product for use in prostate cancer in 2023. rhPSMA compounds for potential therapeutic use are investigational and have not received regulatory approval.

Indication and Important Safety Information About POSLUMA

INDICATION

POSLUMA (flotufolastat F 18) injection is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer

with suspected metastasis who are candidates for initial definitive therapy
with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level
IMPORTANT SAFETY INFORMATION

Image interpretation errors can occur with POSLUMA PET. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. The performance of POSLUMA for imaging metastatic pelvic lymph nodes in patients prior to initial definitive therapy seems to be affected by serum PSA levels and risk grouping. The performance of POSLUMA for imaging patients with biochemical evidence of recurrence of prostate cancer seems to be affected by serum PSA levels. Flotufolastat F 18 uptake is not specific for prostate cancer and may occur in other types of cancer, in non-malignant processes, and in normal tissues. Clinical correlation, which may include histopathological evaluation, is recommended.
Risk of Image Misinterpretation in Patients with Suspected Prostate Cancer Recurrence: The interpretation of POSLUMA PET may differ depending on imaging readers, particularly in the prostate/prostate bed region. Because of the associated risk of false positive interpretation, consider multidisciplinary consultation and histopathological confirmation when clinical decision-making hinges on flotufolastat F 18 uptake only in the prostate/prostate bed region or only on uptake interpreted as borderline.
POSLUMA use contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Advise patients to hydrate before and after administration and to void frequently after administration. Ensure safe handling to minimize radiation exposure to the patient and health care providers.
The adverse reactions reported in ≥0.4% of patients in clinical studies were diarrhea, blood pressure increase and injection site pain.
Drug Interactions: androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of flotufolastat F 18 in prostate cancer. The effect of these therapies on performance of POSLUMA PET has not been established.
To report suspected adverse reactions to POSLUMA, call 1-844-POSLUMA (1-844-767-5862) or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Full POSLUMA prescribing information is available at www.posluma.com/prescribing-information.pdf.

On January 25, 2024 Domain Therapeutics ("Domain" or "the Company"), a clinical-stage global biopharmaceutical company developing innovative drug candidates in immuno-oncology targeting G Protein-Coupled Receptors (GPCRs), reported that it has been awarded a grant as part of the Hospital-University Research in Health (RHU) SPRINT consortium (Press release, Domain Therapeutics, JAN 25, 2024, https://www.domaintherapeutics.com/domain-therapeutics-awarded-hospital-university-research-in-health-rhu-sprint-consortium-grant-to-progress-its-proprietary-ccr8-antibody-candidate-to-the-clinic/ [SID1234639474]). The €30 million consortium project will be supported by a nearly €10 million grant from the Agence Nationale de la Recherche (ANR) as part of the France2030 investment plan, shared between the academic and private partners to progress precision medicines, including moving Domain’s DT-7012 to the clinic.

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The SPRINT project aims to revolutionize the management of patients with CTCL and deliver a new cure paradigm as a standard-of-care. CTCL affects about one in 100,000 adults worldwide each year, nearly tripling in last 30 years. The impact on the quality of life of patients is severe, and the median overall survival rate is less than 5 years in the advanced stages. There is no clear understanding of the underlying factors guiding disease progression.

The multidisciplinary SPRINT consortium gathers internationally renowned physicians and researchers as well as drug discovery and artificial intelligence specialists to investigate the immune tumor microenvironment (TME) of CTCL, understand the mechanism of immuno-resistance, develop a non-invasive prognostic tool and bring new innovative therapeutic solutions to the clinic. The group includes five world-class academics:
UPCité, INSERM, Hospices Civils de Lyon, AP-HP, CHU Bordeaux, two highly innovating companies (Domain Therapeutics and TheraPanacea), while being endorsed by Medicen, the European Reference Network for Rare Hematological Diseases (EuroBloodNet), the French Study Group on Cutaneous Lymphomas (GFELC) – a national network supported by the French National Cancer Institute (INCa), and the patients association ELLyE

Domain and the SPRINT consortium will utilize a triad approach, building upon previous discoveries of extensive investigation into the TME in CTCL, including:

Implementation of an innovative strategy to improve treatment-agnostic early prognostication, through an effective synergy of domain-driven and data-driven artificial intelligence
Validation of a molecular signature of response to mAbs
Innovative drug development targeting tumor cells and the TME in the mechanisms of resistance with mAbs to provide long-term responses
Dr. Stephan Schann, Vice-President of Research at Domain Therapeutics, commented: "Cutaneous T-cell lymphoma is a rare type of cancer, and is largely considered an incurable disease with only few patients responding to current treatments. The grant that we have been awarded by the RHU SPRINT consortium will support the progress of DT-7012, an anti-CCR8 monoclonal antibody which has incredible potential as a best-in-class therapeutic, into the clinic. We are proud to take part in the RHU SPRINT consortium as we aim to turn more non-responder patients into responders."

Professor Adèle de Masson, RHU SPRINT Project Coordinator at Saint-Louis Hospital, Paris, said: "I would like to thank the Agence Nationale de la Recherche (ANR) for this significant support. There is a need for new treatments to address the severe impact on quality of life that cutaneous T-cell lymphoma has on patients, ranging from skin damage to secondary infections, pain, and fatigue, and survival rates. I am hopeful that Domain Therapeutics and the other recipients of the RHU SPRINT consortium grants will help improve the lives of CTCL patients worldwide and I look forward to the outcomes."

Dr Anthony Johnson, President and CEO, Domain Therapeutics, said: "We are extremely pleased for the support and further validation from the RHU for our GPCR targeting immuno-oncology pipeline. Domain was already awarded a first RHU grant, RHU CONDOR for Sarcoma, in the previous campaign, leveraging another proprietary asset. Being successful two consecutive years is unique and highlights the excellence of our science and collaborators. We are excited to work with the government and our partners in this second consortium, RHU SPRINT."

Domain previously announced the nomination of novel drug candidate DT-7012, an anti-CCR8 monoclonal antibody depleting tumor-infiltrating regulatory T cells (Tregs), with best-in-class potential in CTCL and solid tumors. Domain’s target is a highly strategic approach to derive efficient novel immunotherapies that increase the clinical success rate of treatments in non-responding patients with cancer, and the Company expects to start a Phase I study of DT-7012 by mid-2025.