On March 21, 2024 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a clinical stage biotechnology company whose proprietary INTASYL siRNA gene silencing technology is designed to make immune cells more effective in killing tumor cells, reported it is presenting new data about INTASYL on March 21st (Press release, Phio Pharmaceuticals, MAR 21, 2024, View Source [SID1234641354]). The event is scheduled to take place at the 10th Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference (ITOC10), which will be held in Munich, Germany from March 21-23, 2024.

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The poster, Enhancing NK cell cytotoxicity against tumor cells with a novel self-delivering RNAi compound targeting Cbl-b, reveals new preclinical data demonstrating the potential of treatment with INTASYL self-delivering siRNA Compound PH-905, formerly known as Compound 27547, to improve function of natural killer (NK) cells. The data reveals a consistent silencing of Cbl-b mRNA, which has been shown to limit NK cell activation. Cytotoxic activity of NK cells against K562 (Chronic Myelogenous Leukemia) cancer cells was also increased. By reducing the expression of Cbl-b, INTASYL promotes NK cell activation and proliferation. These preclinical data demonstrate the potential of INTASYL Compound PH-905 to improve Adoptive Cell Therapy (ACT) by targeting and silencing Cbl-b. This may result in a more effective cell therapy for hematological malignancies.

"These data underscore the versatility and potential of Phio’s INTASYL siRNA technology," said Phio’s President & CEO Robert Bitterman. "It offers a strategy to enhance the effectiveness of ACT therapies in hematological malignancies."

The preclinical data demonstrate the following:

INTASYL self-delivering RNAi compound PH-905 effectively targets and silences Cbl-b in primary NK cells without negative impact on their viability.
Silencing of Cbl-b results in increased proliferation of primary NK cells.
INTASYL silencing of Cbl-b in primary NK cells enhanced their functional cytotoxicity towards tumor cells.
Silencing of Cbl-b leads to enhanced fitness of NK cells through increased expression of CD98 and CD25, potentially improving NK metabolism and promoting activation in response to IL-2.
INTASYL compound PH-905 may be used to improve the anti-tumor response of NK cells to provide a more effective cell therapy for cancer treatment.
Presentation Details are as follows:
Title: Enhancing NK cell cytotoxicity against tumor cells with a novel self-delivering
RNAi compound targeting Cbl-b
Poster Number: P01.03
Topic: 01.Emerging concepts / New Agents
Presenting Author: Melissa Maxwell
Date and Time: 18:00 hrs Thursday, March 21, 2024
18:00-19:00 hrs Friday, March 22, 2024
Location: Ludwig Maximilian University Campus Großhadern,
Lecture Room 3, Marchioninistrasse 15
81377 Munich, Germany

On March 21, 2024 Turnstone Biologics Corp. ("Turnstone" or the "Company") (Nasdaq: TSBX), a clinical-stage biotechnology company developing a differentiated approach to treat and cure patients with solid tumors by pioneering selected tumor-infiltrating lymphocyte (Selected TIL) therapy, reported financial results for the fourth quarter and full year ended December 31, 2023, and provided recent business highlights (Press release, Turnstone Biologics, MAR 21, 2024, View Source [SID1234641352]).

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"2023 marked a transformative year for Turnstone Biologics in which we transitioned into a publicly traded company and continued to advance our pipeline through clinical development. We are encouraged by the increasing momentum in the TIL landscape that paves the way for next-generation approaches like our Selected TIL therapy, which is designed to create a TIL product with a significantly greater population of potent tumor-reactive T cells, which we believe is the key to extending their therapeutic potential to high unmet medical needs in solid tumors beyond melanoma," said Sammy Farah, M.B.A., Ph.D., Turnstone’s President and Chief Executive Officer. "In 2024, we look forward to generating clinical data that potentially highlights the differentiation of our platform and supports further development of our lead asset, TIDAL-01, which is currently being evaluated in Phase 1 studies in patients with colorectal cancer, head and neck squamous cell carcinoma, breast cancer, uveal melanoma, and cutaneous melanoma. We remain on-track to share initial clinical data for TIDAL-01 in mid-2024 and we believe we are well-positioned for another year of meaningful progress for our organization."

Fourth Quarter and Recent Business Highlights

Advancing TIDAL-01 in Multiple Phase 1 Clinical Trials and Expanding of Targeted Solid Tumor Indications. TIDAL-01 employs an unbiased identification and functional screening process to isolate and selectively expand the greatest breadth of tumor-reactive TILs from the patient’s tumor. Turnstone believes TIDAL-01 can expand the utility of TIL therapy to solid tumor types where first-generation TILs have not to date shown objective responses in clinical trials and is pursuing several indications with critical unmet need, potentially enabling meaningful therapeutic differentiation. Recently, Turnstone expanded their trials to evaluate additional solid tumor types in addition to the existing indications of breast cancer and uveal melanoma. The multi-site STARLING trial protocol has been amended to cover head and neck squamous cell carcinoma (HNSCC), and the H. Lee Moffitt Cancer Center and Research Institute sponsored trial has been expanded to include colorectal cancer (CRC) and HNSCC. Turnstone expects to provide an initial clinical update across these trials in mid-2024.

Preclinical Data Presentations at the 2023 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting Support Ongoing Clinical and Preclinical Efforts. In November 2023, Turnstone presented preclinical data on its Selected TIL therapies, including the demonstration of the feasibility of selecting and expanding tumor-reactive TIL as further evidence for the potential of TIDAL-01 as a treatment option for patients with colorectal and gastric cancers. Turnstone also presented on its next Selected TIL program from its development pipeline, TIDAL-02, which seeks to utilize a novel direct selection method, genetically engineered to rapidly select for the greatest breadth of tumor-reactive T cells.

Strengthened Company’s Scientific Advisory Board. In October 2023, Turnstone appointed Jeffrey S. Weber, M.D., Ph.D., to its Scientific Advisory Board. Dr. Weber, a world-renowned thought leader with extensive experience in innovative immunotherapies for solid tumors, currently serves as Deputy Director of the Perlmutter Cancer Center and Co-Director of the Melanoma Research Program at the New York University-Langone Cancer Center.

Fourth Quarter 2023 Financial Results

Cash, Cash Equivalents and Short-Term Investments: As of December 31, 2023, cash, cash equivalents and short-term investments were $94.8 million. The Company expects that the combined cash, cash equivalents and short-term investments will be sufficient to fund its operations into the second quarter of 2025.

Research and Development (R&D) Expenses: R&D expenses for the three months ended December 31, 2023, were $13.6 million, compared to $20.2 million for the same period in 2022. The decrease was due primarily to decreases in pre-clinical and regulatory costs, personnel-related costs, and manufacturing expenses due to the termination of the discovery, collaboration and license agreement entered into on November 7, 2019, with Takeda Oncology for certain viral immunotherapy candidates offset by an increase due to ramp up of TIDAL-01 activities.

General and Administrative (G&A) Expenses: G&A expenses for the three months ended December 31, 2023, were $4.4 million, compared to $4.4 million for the same period in 2022.

Net Loss: Net loss for the three months ended December 31, 2023, was $16.5 million, compared to net loss of $13.7 million for the same period in 2022.

Full Year 2023 Financial Results

Cash, Cash Equivalents and Short-Term Investments: For the full year ended December 31, 2023, cash, cash equivalents and short-term investments were $94.8 million.

Research and Development (R&D) Expenses: R&D expenses for the full year ended December 31, 2023, were $60.5 million, compared to $86.7 million for the prior year period. The decrease was due primarily to decreases in pre-clinical and regulatory and manufacturing expenses due to the termination of the discovery, collaboration and license agreement entered into on November 7, 2019, with Takeda Oncology for certain viral immunotherapy candidates offset by an increase in personnel-related costs and costs due to ramp up of TIDAL-01 activities.

General and Administrative (G&A) Expenses: G&A expenses for the full year ended December 31, 2023, were $17.8 million, compared to $18.2 million for the prior year period. We anticipate that G&A expenses will remain stable as we support public company operations.

Net Loss: Net loss for the full year ended December 31, 2023, was $55.2 million, compared to net loss of $30.8 million for the prior year period.

On March 21, 2024 Theratechnologies Inc. ("Theratechnologies" or the "Company") (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported moving to the next dose level in Part 3 of its Phase 1 clinical trial of sudocetaxel zendusortide in patients with advanced ovarian cancer (Press release, Theratechnologies, MAR 21, 2024, View Source [SID1234641351]). The study’s Medical Review Committee (MRC) has deemed the dose level in the first cohort of patients safe and has approved initiation of the next cohort with an increased dose, in accordance with the updated dose optimization protocol. Study centers are now actively recruiting patients for the second cohort, with one patient already enrolled and treated with the higher dose.

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"We are encouraged by the safety and tolerability of the sudocetaxel zendusortide regimen in the first cohort of six patients in Part 3 of the Phase 1 trial," said trial investigator Ira Winer, M.D., Ph.D., FACOG, a member of the Gynecologic Oncology and Phase 1 Clinical Trials Multidisciplinary Teams at Karmanos Cancer Center and Associate Professor of Oncology at Wayne State University. "We will continue to enroll and monitor patients as we further investigate this novel peptide-drug conjugate in individuals with advanced, platinum-resistant ovarian cancer, a population with high unmet medical need."

Part 3 of the Phase 1 study is intended to assess the optimal dose and schedule of sudocetaxel zendusortide, which is being administered on three consecutive weeks followed by one week of rest on Days 1, 8, and 15 of each 28-day cycle. The dose for the initial six patients was 1.75 mg/kg/dose and the dose for the next cohort of patients is 2.50 mg/kg/dose. The MRC approved initiation of the second cohort following attainment of the threshold of one or less dose-limiting toxicities in the first cohort. The study’s updated protocol defines DLTs as any Grade 3 or greater toxicity, within the first cycle and any worsening of peripheral neuropathy to Grade 3 or 4 within a three-month period.

"Initiation of treatment at the next dose level is an important milestone for Part 3 of the Phase 1 study and will allow us to further characterize sudocetaxel zendusortide as a potentially viable therapy for individuals with advanced ovarian cancer," commented Christian Marsolais, Ph.D., Senior Vice President and Chief Medical Officer at Theratechnologies. "We welcome discussions with potential partners interested in helping to advance development of this novel peptide-drug conjugate."

Theratechnologies completed enrollment of the first cohort of six patients in Part 3 of the Phase 1 trial in February 2024, and dosed the first patient in October 2023. The U.S. Food and Drug Administration (FDA) approved the amended trial protocol in June 2023. Further details about the study design, participation criteria and contact information for the sites can be found at: View Source

About Sudocetaxel Zendusortide (TH1902) and SORT1+ Technology

Sudocetaxel zendusortide is a first-of-its-kind sortilin receptor (SORT1)-targeting peptide-drug conjugate, and the first compound to emerge from the Company’s broader licensed oncology platform. A new chemical entity, sudocetaxel zendusortide employs a cleavable linker to conjugate (attach) a proprietary peptide to docetaxel, a well-established cytotoxic chemotherapeutic agent used to treat many cancers. The FDA granted Fast Track designation to sudocetaxel zendusortide as a single agent for the treatment of all sortilin-positive recurrent advanced solid tumors that are refractory to standard therapy. Sudocetaxel zendusortide is currently being evaluated in a Phase 1 clinical trial.

Theratechnologies has established the SORT1+ Technology platform as an engine for the development of PDCs that target SORT1, which is expressed in multiple tumor types. SORT1 is a "scavenger" receptor that plays a significant role in protein internalization, sorting, and trafficking. Expression of SORT1 is associated with aggressive disease, poor prognosis, and decreased survival. It is estimated that SORT1 is expressed in 40% to 90% of endometrial, ovarian, colorectal, triple-negative breast (TNBC), and pancreatic cancers, making this receptor an attractive target for anticancer drug development.

On March 21, 2024 Satya reported to present preclinical profile of its PARG inhibitors at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting – April 5-10, San Diego, CA (Press release, SATYA Pharma Innovations, MAR 21, 2024, View Source [SID1234641350]).

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March 21, 2024
3:31 pm
Abstract title

Preclinical profile of novel and potent small molecule inhibitors of PARG

Poster number

7112

Session title

DNA Damage and Repair

Session date and time

April 10, 9:00 AM – 12:30 PM

Session category

Experimental and Molecular therapeutics

Abstract title: Preclinical profile of novel and potent small molecule inhibitors of PARG

Abstract:
Poly(ADP-ribose) glycohydrolase (PARG) is primary enzyme involved in the dePARylation process of DNA repair, specifically in the single strand break repair (SSBRs). PARG is a macrodomain protein with exo- and endo-glycohydrolase activity that liberates free ADP-ribose and PAR chains, respectively. It interacts with various Poly(ADP-ribose) polymerase (PARP) proteins to facilitate appropriate and timely DNA repair. The balance between PARP and PARG activity is essential for efficient DDR. Inhibition of PARG lead to altered DNA repair in cancer cells. We have identified highly potent PARG inhibitors with picomolar IC50 in biochemical assay. PARG is the primary enzyme for dePARylation and accounts for 90% of dePARylation activity. Treatment of HCC-1806 cells with PARG inhibitors showed dose dependent increase of PARylation signature, with sub micromolar IC50 . Compounds also demonstrate significant functional, anti-proliferative activity in ovarian and breast cancer cell lines besides a favourable ADME profile. Further pharmacokinetic and pharmacodynamic characterization of the identified hits is currently in progress.

On March 21, 2024 Pyxis Oncology, Inc. (Nasdaq: PYXS), a clinical stage company focused on developing next generation therapeutics to target difficult-to-treat cancers, reported financial results for the year and quarter ended December 31, 2023, and provided a corporate update (Press release, Pyxis Oncology, MAR 21, 2024, View Source [SID1234641347]).

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PYX-201, a first-in-concept tumor stroma targeting antibody-drug conjugate (ADC) against the stromal Extradomain-B Fibronectin (EDB+FN) target, has dosed 37 patients in 6 cohorts since initiating the Phase 1 trial in March 2023. PYX-201 recently cleared the 21-day Dose Limiting Toxicity (DLT) observation period for ten subjects in Cohort 6 at a dose of 5.4 mg/kg. The Dose Escalation Steering Committee (DESC) met on March 19, 2024, and voted to escalate dosing into Cohort 7 at a dose of 8 mg/kg.

PYX-201 has been well tolerated to date, with no significant evidence of target mediated toxicities experienced by the 37 subjects enrolled and dosed. Approximately 54% of subjects have experienced grade 2, and 6% of subjects have experienced grade 3 treatment emergent adverse events (TEAEs). No subjects have reported TEAEs leading to dosing delay or study drug discontinuation. Another 10-15 subjects are likely to be dosed at either Cohort 7 (8 mg/kg) or future higher dose level cohorts, should PYX-201’s profile continue to support further dose escalation.

As we continue to dose escalate, we are focusing ongoing enrollment on four tumor types of high interest, identified through the assessment of several factors, including, but not limited to, IHC target expression data, stromal volume, and unmet medical need: head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), ovarian cancer, and pancreatic ductal adenocarcinoma cancer (PDAC).

"We believe the encouraging PYX-201 safety profile observed to date likely reflects the specificity of target expression within tumor tissue and the potential for a wider therapeutic index given the novel mechanism of action within the tumor microenvironment," said Lara S. Sullivan, M.D., President and Chief Executive Officer of Pyxis Oncology. "The tumor stroma is a prominent component of many solid tumors, and we believe that PYX-201 could have broad utility in many cancer settings. The global study remains on track with continued investigator enthusiasm and ease of enrollment, and we look forward to announcing initial results in the fall of 2024 with final timing dependent on ongoing continued dose escalation and finalization of subject scans."

Dr. Sullivan added, "We are also continuing to enroll our Phase 1 study evaluating PYX-106, a fully human immunotherapy antibody candidate that is designed to block the activity of Siglec-15 in subjects with NSCLC and other tumors of interest. We look forward to initial results from this program in 2H 2024."

Program and Corporate Updates

•
PYX-201 in the PYX-201-101 trial: To date, 37 subjects have been dosed, and we are currently enrolling Cohort 7 at 8 mg/kg. In the fall of 2024, we plan to report efficacy, safety, pharmacokinetics (PK), pre-clinical insights, the plan for the next development phase, and the likely timing of associated catalysts.
•
PYX-106 in the PYX-106-101 trial: Phase 1 trial focusing on NSCLC and other tumor types. Study dosing is ongoing with 21 subjects dosed to date and Cohort 5 is fully enrolled at 8 mg/kg administered once every two weeks. Preliminary data is anticipated in 2H 2024.
•
In Feb. 2024, completed a $50M PIPE with participation from new and existing institutional investors, including Deep Track Capital, Ridgeback Capital Investments L.P., Blue Owl Healthcare Opportunities, Laurion Capital Management, and StemPoint Capital L.P. Pyxis Oncology intends to use the proceeds to fund the continued development of PYX-201 and for working capital and general corporate purposes.

Anticipated Upcoming Milestones

•
PYX-201: Report preliminary Phase 1 data and PK/PD results in fall of 2024
•
PYX-106: Report preliminary Phase 1 data and PK/PD results in 2H 2024

Full Year and Q4 2023 Financial Results

•
As of December 31, 2023, Pyxis Oncology had cash and cash equivalents, including restricted cash, and short-term investments of $120.8 million. Following the end of fiscal year 2023, we raised gross proceeds of $10.8 million via ATM offering and completed $50 million of private placement. Pyxis Oncology expects to have the resources to fund operations into 2nd half of 2026.
•
Research and development expenses were $49.6 million for the year ended December 31, 2023, compared to $86.1 million for the year ended December 31, 2022. The decrease was primarily due to a one-time payment of $17.3 million to acquire exclusive licensing rights for the FACT platform, one-time payment of $10 million to acquire licensing rights to PYX-106 and decrease in contract manufacturing costs for drug products and drug substances by $12.5 million in 2022. This decrease was partially offset by a $5.0 million increase in clinical trial related expenses for our ongoing Phase 1 clinical trials for PYX-201 and PYX-106.
•
General and administrative expenses were $32.6 million for the year ended December 31, 2023, compared to $37.4 million for the year ended December 31, 2022. The decrease was primarily related to a reduction in professional and consultant fees partially offset by higher personnel-related expenses, including stock-based compensation.
•
Net loss was $73.8 million, or ($1.85) per common share, for the year ended December 31, 2023, compared to $120.7 million, or ($3.65) per common share, for the year ended December 31, 2022. Net losses for the years ended December 31, 2023 and 2022, included $16.9 million and $15.8 million, respectively, related to non-cash stock-based compensation expense.
•
As of March 20, 2024, the outstanding number of shares of Common Stock of Pyxis Oncology was 58,133,375.