On September 11, 2023 Vergent Bioscience, a clinical-stage biotechnology company developing tumor-targeted imaging agents, and its wholly owned subsidiary Vergent Bioscience Australia Pty Ltd, reported that new data presented at the IASLC 2023 World Conference on Lung Cancer (#WCLC23) suggest the company’s tumor-targeted fluorescent imaging agent is active and can safely be used to detect tumor tissue in the lung with high accuracy (Press release, Vergent Bioscience, SEP 11, 2023, View Source [SID1234635085]). Findings from the Phase 2 surgical study evaluating VGT-309 suggest the investigational agent could improve surgeons’ ability to see difficult-to-find and previously undetected tumors in real time to help optimize patient outcomes.

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"The widespread adoption of minimally invasive lung cancer surgery, coupled with increasing numbers of small tumors being detected, have made it much more challenging for surgeons to see all tumor tissue during surgery," said Gavin M. Wright, Ph.D., associate professor and director of Surgical Oncology, St. Vincent’s Hospital, Melbourne, Australia. "The findings from our study confirm that VGT-309 could enhance the success of minimally invasive surgery by improving tumor visualization and reducing the potential for cancer to be left behind."

The Phase 2 study evaluated the safety and efficacy of VGT-309 in 27 individuals with suspected or proven cancer in the lung who were eligible for surgery. Each patient in the study received a VGT-309 infusion on the day prior to or day of surgery. Following an attempt to identify each tumor using standard surgical techniques, researchers used a commercially available near-infrared (NIR) endoscope to assess the lung for the presence of any additional tumor tissue, which was then confirmed by pathology.

The study findings presented today at the WCLC23 provide compelling evidence that VGT-309 has a high affinity for malignant tissue in the lung, increasing the potential that surgeons can identify all tumor tissue during surgery. Of the 27 participants, 23 had confirmed cancer, one had typical carcinoid, and three had non-neoplastic processes. The following tumor types were visualized intraoperatively with VGT-309 and NIR imaging: non-small cell lung cancer (adenocarcinoma and squamous cell carcinoma), metastatic carcinoma with breast origin, and high-grade sarcoma of epithelioid morphology. In two patients, VGT-309 identified tumor tissue in lymph nodes that was pathologically confirmed to be cancer, resulting in upstaging that could potentially impact patient treatment and outcomes.

VGT-309 appeared to be safe and well tolerated across all dose levels studied, with no infusion reactions and only one patient experiencing a serious adverse event – a transient elevated liver-function test that resolved without intervention.

"This study provides encouraging results demonstrating the clinical performance of VGT-309, including the breadth of tumors the agent can help surgeons visualize and its corresponding potential to enhance outcomes from minimally invasive surgery," said John Santini, Ph.D., president and chief executive officer at Vergent Bioscience. "We look forward to expanding on these results in future studies including our upcoming multi-center Phase 2 clinical trial."

About VGT-309

VGT-309 is a tumor-targeted imaging agent designed to enable a complete product solution for optimal tumor visualization during open, MIS, and robotic-assisted surgical procedures. VGT-309 is delivered to patients by a short infusion several hours before surgery. Invented in Professor Matt Bogyo’s Lab at Stanford University School of Medicine, the molecule binds tightly (i.e., covalently) to cathepsins, a family of proteases that are overexpressed across a broad range of solid tumors. This approach provides distinct clinical advantages and positions VGT-309 as an ideal tumor-imaging agent. VGT-309’s imaging component is the near infrared (NIR) dye indocyanine green (ICG), which is compatible with all commercially available NIR intraoperative imaging systems that support MIS technologies and is the preferred dye to minimize confounding background autofluorescence.

On September 11, 2023 Eikon Therapeutics, Inc., which advances breakthrough therapeutics through the purposeful integration of engineering and science, reported that it has completed the previously announced integration of TLR 7 and 8 co-agonists into its clinical development program, and that it expects to discuss the further development of these molecules with the U.S. Food and Drug Administration (FDA) in the fourth quarter (Press release, Eikon Therapeutics, SEP 11, 2023, View Source [SID1234635084]). Separately, the FDA has cleared IMP1734, a highly selective PARP1 inhibitor developed in partnership with Impact Therapeutics, for Phase 1 study initiation, which will also begin in the fourth quarter.

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"Powered by the contributions of our cross-disciplinary organization, Eikon has made important progress in both our early- and clinical-stage pipeline programs," said Roger M. Perlmutter, M.D., Ph.D., CEO and Board Chair of Eikon Therapeutics. "Our advanced analytical tools have enabled Eikon to capitalize on near-term opportunities to bring new medicines to patients. Irrespective of the precise source of chemical leads, Eikon’s projects employ pioneering protein dynamics visualization systems, coupled with advanced, ML-based, data analysis platforms. These systems, together, are fueling our growth."

Eikon’s most advanced candidate, BDB001, a systemically administered TLR 7 and 8 co-agonist, has been studied in nearly 300 patients with treatment-resistant advanced malignancies, and has demonstrated clinical activity both as a single agent and in combination with PD-(L)1 inhibitors. Eikon believes that adverse experiences associated with BDB001 treatment are manageable using Eikon’s proposed clinical dosing regimen.

Separately, in collaboration with Impact Therapeutics, Eikon is advancing IMP1734, a novel, highly potent, PARP1 inhibitor that shows profound biochemical and cellular selectivity versus PARP2, a related enzyme that is thought to contribute disproportionately to the adverse effect profiles of currently marketed PARP1/2 inhibitors. The extraordinary selectivity of IMP1734 for PARP1 supports clinical study of this agent as monotherapy and in combination with other treatment regimens. Eikon anticipates initiating Phase 1 clinical studies of IMP1734 in the United States and other jurisdictions in the fourth quarter. In addition, Eikon and Impact Therapeutics have together planned initiation of IND-enabling studies for a brain-penetrant PARP1 candidate that will enter Phase 1 clinical trials once these IND-enabling studies are successfully completed and reviewed.

"The continued progress of our clinical-stage programs is a testament to our emerging clinical development organization which includes experienced industry professionals who collectively have contributed to more than 100 U.S. regulatory approvals of new medicines over their careers," said Roy Baynes, M.D., Ph.D., Chief Medical Officer of Eikon Therapeutics. "The recent IND clearance for our lead selective PARP1 inhibitor, and the planned initiation of IND-enabling studies of the brain penetrant molecule, further advance the strategic investments we have made in these unique oncology therapeutics and add to our oncology programs exploring the TLR 7 and 8 co-agonist."

Eikon has applied its proprietary technologies to programs spanning oncology, immunology, and neuroscience at various stages of preclinical development. Among these programs are candidates targeting steroid hormone receptors, WRN inhibition, and VCP modulation. Eikon has also begun lead optimization of androgen receptor antagonists that target increasingly common androgen receptor mutants, with the aim of delivering a therapeutic for treatment-refractory, castrate-resistant prostate cancer.

"The growth of our preclinical discovery programs is benefiting significantly from the engineering and automation that powers our pioneering, single molecule tracking-based, discovery platform. With the ability to capture upwards of one hundred thousand protein trajectories in less than a second, we are now analyzing more than one million experimental conditions per month," said Dan Anderson, Ph.D., Chief Scientific Officer of Eikon Therapeutics. "Through AI and machine learning, we are able to rapidly analyze data and inventory molecular interactions with extraordinary scale and precision to support progress across all our drug discovery programs."

Eikon’s CEO will participate in a fireside chat at Morgan Stanley’s 21st Annual Global Healthcare Conference, Monday, September 11 at 10:40 a.m. EDT. A webcast will be available and can be accessed through the conference website or at www.EikonTx.com/news.

On September 11, 2023 OSE Immunotherapeutics SA reported the peer-reviewed publication in Annals of Oncology* of the randomized Phase 3 clinical trial (Atalante-1**) on T-cell epitope cancer vaccine Tedopi in HLA-A2 positive patients with advanced or metastatic NSCLC in monotherapy in third line NSCLC with secondary resistance to immune checkpoint inhibitors (ICI) (Press release, OSE Immunotherapeutics, SEP 11, 2023, View Source [SID1234635083]).

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Tedopi is a novel T-cell epitope-based cancer vaccine targeting five tumor-associated antigens, an activating and differentiated off-the-shelf immunotherapy expanding tumor specific T-lymphocytes in HLA-A2 cancer patients. The article, titled "Randomized Open-Label Controlled Study of Cancer Vaccine OSE2101 Versus Chemotherapy in HLA-A2-positive Patients with Advanced Non-Small Cell Lung Cancer with Resistance to Immunotherapy: ATALANTE-1" features positive data from the randomized international Phase 3 study showing that novel cancer vaccine Tedopi improves overall survival with a better safety and quality of life profile in monotherapy compared to chemotherapy in HLA-A2 positive patients with advanced or metastatic NSCLC who have progressed at least 12 weeks after sequential treatment with chemotherapy and immune checkpoint inhibitors (ICI).

Prof. Benjamin Besse, Director of Clinical Research at Gustave Roussy Institute (IGR, Villejuif, France), and Principal Investigator of the Atalante-1 clinical trial, commented: "Tedopi is the first cancer vaccine to demonstrate positive results on survival in a randomized Phase 3 trial in advanced and metastatic NSCLC cancer patients in 3rd line. A significant reduction of the risk of death by 41% was achieved with a better safety profile and a maintained quality of life. This study, conducted in patients with secondary resistance to immunotherapy, compared Tedopi monotherapy with standard of care docetaxel or pemetrexed chemotherapies. Further evaluation is clearly warranted in a second line of treatment of advanced and metastatic NSCLC, to potentially make this cancer vaccine available to hard-to-treat patients in failure and with high medical needs."

Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics, commented: "Tedopi is the most advanced therapeutic cancer vaccine in clinical development. These Phase 3 data, demonstrating the promising effects, have now been validated in the internationally recognized journal ‘Annals of Oncology’, a major achievement for all involved so, in particular, we’d like to thank warmly the investigators, the patients and their families for their commitment. This Phase 3 positive monotherapy data and moreover the recently announced positive Phase 1 and 2 results using other personalized cancer vaccines in combination to treat resected melanoma or pancreatic cancer patients, highlight the promise of this new therapeutic class of vaccines. The clinical value of our results, re-activating specifically the anti-tumor immune responses, is particularly interesting in patients showing immune escape from checkpoint inhibitors. The confirmatory pivotal Phase 3 trial in preparation (first patient expected early 2024) is planned to support the regulatory registration of Tedopi in secondary resistance to immune checkpoint inhibitors, this time in second line NSCLC treatment."

Main results of the first Phase 3 clinical trial of Tedopi in HLA-A2+ patients with NSCLC

This Phase 3 clinical trial has demonstrated a significant therapeutic benefit in patients with secondary

resistance (1) to immune checkpoint inhibitors (ICI) defined as patients with failure to platinum-based chemotherapy followed by a minimum of 12 weeks ICI treatment (main analysis of the trial). Tedopi demonstrated a favorable benefit/risk ratio versus standard of care (SoC) docetaxel or pemetrexed in advanced HLA-A2+ NSCLC patients with secondary resistance to ICI.

The main results were:

Improved efficacy

1. Overall survival (primary endpoint) was statistically significantly improved for Tedopi:
HR=0.59 (95% CI: 0.38, 0.91) in favor of the Tedopi arm, reduced risk of death by 41%.
44.4% overall survival rate at 1 year with Tedopi versus 27.5% with chemotherapy. A clinically meaningful gain in median overall survival of 3.6 months in favor of the Tedopi arm with Tedopi OS at 11.1 months versus 7.5 months for SoC (p=0.017).

2. Post progression survival was also significantly longer in the Tedopi arm (7.7 months versus 4.6 months; p=0.004, HR=0.46).

Improved safety profile and Quality of Life

The ECOG performance status(2), of maintained general health condition with time to ECOG deterioration was significantly longer in the Tedopi arm (9.0 months versus 3.3 months; p=0.006; HR=0.43).
A better quality of life was observed with Tedopi (p= 0.04). (Global health status: p=0.045; Role Functioning: p=0.025).
A good tolerance profile of Tedopi with fewer Severe Adverse Events grade 3-5 (Tedopi 38% vs SoC 68%, p<0.001). No Treatment Emergent Adverse Effects of concern in the Tedopi arm.
(1) Secondary resistance is defined as failure after a minimum of 12 weeks of Immune checkpoint inhibitor given in sequential chemotherapy – checkpoint inhibitors treatment (Kluger HM et al; Journal for immunoTherapy of Cancer 2020 Defining tumor resistance to PD-1 pathway blockade: recommendations from the first meeting of the SITC (Free SITC Whitepaper) Immunotherapy Resistance Taskforce)
(2) The ECOG score is a performance scale used to quantify the general health condition of a patient. It is subdivided into 5 grades from 0 to 5, ranging from fully active (0) to fully disabled, then to death (5).

ABOUT OSE Immunotherapeutics

OSE Immunotherapeutics is a biotech company dedicated to developing first-in-class assets in immuno-oncology and immuno-inflammation.

The Company’s current well-balanced first-in-class clinical pipeline includes:

Tedopi (immunotherapy activating tumor specific T-cells, off-the-shelf, neoepitope-based): this cancer vaccine is the Company’s most advanced product; positive results from the Phase 3 trial (Atalante 1) in Non-Small Cell Lung Cancer patients in secondary resistance after checkpoint inhibitor failure. Other Phase 2 trials, sponsored by clinical oncology groups, of Tedopi in combination are ongoing in solid tumors.
OSE-279 (anti-PD1): ongoing Phase 1/2 in solid tumors or lymphomas (first patient included). OSE-279 is the backbone therapy of the BiCKI platform.
OSE-127 – lusvertikimab (humanized monoclonal antibody antagonist of IL-7 receptor); ongoing Phase 2 in Ulcerative Colitis (sponsor OSE Immunotherapeutics); ongoing preclinical research in leukemia (OSE Immunotherapeutics).
FR-104/VEL-101 (anti-CD28 monoclonal antibody): developed in partnership with Veloxis Pharmaceuticals, Inc. in transplantation; ongoing Phase 1/2 in renal transplant (sponsor Nantes University Hospital); Phase 1 ongoing in the US (sponsor Veloxis Pharmaceuticals, Inc.).
OSE-172/BI 765063 (anti-SIRPα monoclonal antibody on CD47/SIRPα pathway) developed in partnership with Boehringer Ingelheim in advanced solid tumors; positive Phase 1 dose escalation results in monotherapy and in combination, in particular with anti-PD-1 antibody ezabenlimab; international Phase 1b ongoing clinical trial in combination with ezabenlimab alone or with other drugs in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) and hepatocellular carcinoma (HCC).
OSE Immunotherapeutics expects to generate further significant value from its two proprietary drug discovery platforms, which are central to its ambitious goal to deliver next-generation first-in-class immunotherapies:

BiCKI platform focused on immuno-oncology (IO) is a bispecific fusion protein platform built on the key backbone component of anti-PD1 combined with a new immunotherapy target to increase anti-tumor efficacy. BiCKI-IL-7 is the most advanced BiCKI candidate targeting anti-PD1xIL-7.
Myeloid platform focused on optimizing the therapeutic potential of myeloid cells in IO and immuno-inflammation (I&I). OSE-230 (ChemR23 agonist mAb) is the most advanced candidate generated by the platform, with the potential to resolve chronic inflammation by driving affected tissues to tissue integrity.

On September 11, 2023 CymaBay Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on developing innovative therapies for liver and other chronic diseases with high unmet medical need, reported the pricing of its previously announced underwritten public offering of common stock and pre-funded warrants (Press release, CymaBay Therapeutics, SEP 11, 2023, View Source [SID1234635081]). CymaBay is selling 12,551,080 shares of common stock and, in lieu of common stock to certain investors, pre-funded warrants to purchase 583,771 shares of common stock in the offering. The shares of common stock are being sold at a public offering price of $17.13 per share, and the pre-funded warrants are being sold at a public offering price of $17.1299 per underlying share. The gross offering proceeds to CymaBay from this offering are expected to be approximately $225 million, before deducting the underwriting discount and other estimated offering expenses, and excluding the exercise of any pre-funded warrants. The pre-funded warrant has an exercise price of $0.0001 per share. All shares of common stock and pre-funded warrants to be sold in the offering are being offered by CymaBay. CymaBay has granted the underwriters a 30-day option to purchase up to an additional 1,970,227 shares of its common stock at the public offering price per share less underwriting discounts and commissions. The offering is expected to close on September 14, 2023, subject to the satisfaction of customary closing conditions.

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CymaBay anticipates using the net proceeds from the offering to fund ongoing development of seladelpar, including clinical trials targeting market expansion, and for working capital and general corporate purposes.

Piper Sandler, Raymond James, Cantor and LifeSci Capital are acting as the joint book-running managers for the offering. BTIG is acting as the lead manager for the offering.

The securities described above are being offered by CymaBay pursuant to a shelf registration statement filed with the Securities and Exchange Commission (the "SEC"). A preliminary prospectus supplement and accompanying prospectus related to the offering has been filed, and a final prospectus supplement and accompanying prospectus related to the offering will be filed, with the SEC and are or will be available on the SEC’s website at www.sec.gov. Copies of the prospectus supplement and the accompanying prospectus relating to this offering may be obtained, when available, from: Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, Minnesota 55402, by telephone at (800) 747-3924, or by email at [email protected]; Raymond James & Associates, Inc., Attention: Equity Syndicate, 880 Carillon Parkway, St. Petersburg, Florida 33716, by telephone at (800) 248-8863, or by e-mail at [email protected]; Cantor Fitzgerald & Co., Attention: Capital Markets, 110 East 59th Street, 6th Floor, New York, New York 10022, or by e-mail at [email protected]; or LifeSci Capital LLC, Attention: Syndicate Prospectus Department, 250 West 55th Street, 34th Floor, New York, NY 10019, by email at [email protected] or by telephone at (646) 876-5059.

This press release shall 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 registration or qualification under the securities laws of any such state or jurisdiction.

On September 11, 2023 PeproMene Bio, Inc., a clinical-stage biotech company developing novel therapies to treat cancers and immune disorders, reported that the first dose cohort of its phase 1 relapsed or refractory B-cell Non-Hodgkin Lymphoma (r/r B-NHL) clinical trial of PMB-CT01 (BAFFR-CAR T Cells) has been completed (Press release, PeproMene Bio, SEP 11, 2023, View Source [SID1234635080]). No Dose Limiting Toxicity (DLT) was observed, and the study has been cleared to proceed with the next cohort.

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The PMB-102 trial is taking place at City of Hope, one of the largest cancer research and treatment organizations in the nation. PeproMene licensed intellectual property relating to PMB-CT01 from City of Hope, which developed the therapy.

In the first cohort, administration of 50×106 PMB-CT01 has been extremely well tolerated. Among three treated patients, all three experienced only grade 1 cytokine release syndrome ("CRS") and two had grade 1 immune effector cell-associated neurotoxicity syndrome ("ICANS") with full recovery. The Overall Response Rate is 100% (two Complete Response and one Partial Response) at one-month post treatment. Two patients with mantle cell lymphoma had progressed after conventional CD19 CAR T-cell treatment prior to enrollment on PMB-CT01.

"We are pleasantly surprised and thrilled to see such minimal toxicity associated with such a high response rate in heavily pretreated patients who have failed 3-10 prior lines of therapy, including FDA-approved CD19 CAR T-cells", said Elizabeth Budde, M.D., Ph.D., the principal investigator of this single-center, dose escalation trial (NCT05370430) and associate professor at City of Hope, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation.

"Despite high initial efficacy of CD19-CAR T cell therapy for B-cell lymphoma and leukemia, a significant number of patients still relapse after CD19-CAR T treatment, highlighting the urgent unmet medical need," said Larry W. Kwak, M.D., Ph.D., vice president and deputy director of City of Hope’s Comprehensive Cancer Center and PeproMene’s scientific founder and compensated chair of its Scientific Advisory Board. Kwak has an equity interest in PeproMene. "Unlike CD19, BAFF-R signaling is required for B cell growth and survival, so it may limit the capacity of B cell tumors to evade therapy by loss of BAFF-R expression. I hope BAFFR-CAR T therapy will offer a clinically meaningful, new option for patients."

"Although still in early stage, we are encouraged by the initial observation of acceptable safety and preliminary efficacy in the first dose cohort of PMB-CT01 treated B-NHL patients. All 3 treated patients (2 progressed after CD19 CAR T therapy and 1 with CD19/CD20 negative lymphoma) responded to PMB-CT01 treatment," said Hazel Cheng, Ph.D., COO of PeproMene. "These clinical outcomes are consistent with City of Hope preclinical research data published in Science Translational Medicine in 2019, which showed that PMB-CT01 (BAFFR-CAR T Cells) could overcome CD19 antigen loss in B-cell malignancies."

About PMB-CT01

PMB-CT01 is a first-in-class BAFFR-targeted, autologous CAR T cell therapy. BAFF-R (B Cell Activating Factor Receptor), a tumor necrosis factor (TNF) receptor superfamily member, is the main receptor for BAFF expressing almost exclusively on B cells. Since BAFF-R signaling promotes normal B-cell proliferation and appears to be required for B-cell survival, it is unlikely tumor cells could escape immune responses via loss of BAFF-R antigen. This unique characteristic makes BAFF-R CAR T therapy a great potential treatment of B cell malignancies. BAFF-R CAR-T was constructed using the anti-BAFF-R scFv (single-chain fragment variable) antibodies with the 2nd generation signaling domains containing CD3ζ and 4-1BB. Our research has found that BAFFR-CAR T cells kill human lymphomas and leukemias in vitro as well as in animal models. PeproMene has licensed intellectual property relating to PMB-CT01, from City of Hope.