On March 22, 2023 Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, reported the successful dosing of first patient in the U.S. Phase I Study of TST003 (NCT05731271), its first-in-class, high affinity humanized monoclonal antibody targeting Gremlin1, for the treatment of solid tumors (Press release, Transcenta, MAR 22, 2023, View Source [SID1234629174]).

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NCT05731271 is an open-label, dose escalation, FIH study designed to evaluate the safety, tolerability, and pharmacokinetics profile of TST003 as a treatment in patients with solid tumors.

TST003 is a high affinity monoclonal antibody targeting Gremlin1, a member of the TGF-β superfamily. Gremlin1 protein is a highly conserved secreted protein and has shown to play important roles during embryonic development and promote epithelial mesenchymal transition. Gremlin1 is upregulated in multiple solid tumors. TST003 has demonstrated promising single agent and combination activities in patient-derived xenograft tumor models from the difficult-to-treat solid tumors resistant to checkpoint inhibitors including castration resistant prostate cancer and microsatellite stable colorectal cancer.

"The enrollment and dosing of the first patient in the U.S. marks a very significant milestone for TST003: our carefully designed Phase 1 will provide the necessary clinical and translational data to achieve the full potential of targeting Gremlin1 as a single agent or in combinations with standard of care, in particular in indications with high unmet need like MSS CRC or CRPC." said Dr. Caroline Germa, Transcenta’s Executive Vice President, Global Medicine Development and Chief Medical Officer.

On March 22, 2023 Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, reported that two preclinical studies in relation to TST003, a First-in-Class mAb Targeting GREMLIN-1, and TST010, an ADCC enhanced anti-CD25 mAb will be presented as posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 (Press release, Transcenta, MAR 22, 2023, View Source [SID1234629173]). This year’s meeting will be held from April 14-19, 2023, in Orlando, Florida, USA.

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The AACR (Free AACR Whitepaper) Annual Meeting is the focal point of the cancer research community, where scientists, clinicians, other health care professionals, survivors, patients, and advocates gather to share the latest advances in cancer science and medicine from institutions all over the world.

A brief summary of the presentations is as follows:
Title: The Preclinical Characterization of TST003, a First-in-Class mAb Targeting GREMLIN-1 Overexpressed by Cancer-Associated Fibroblasts and Tumor Cells
Abstract#: 465
Session Category: Experimental and Molecular Therapeutics
Session Title: New Drug Targets
Session Date and Time: Sunday Apr 16, 2023 1:30 PM – 5:00 PM (EDT)

Title: ADCC enhanced anti-CD25 mAb (TST010) exhibited potent anti-tumor activity by depleting Treg cells and increasing CD8+T/Treg ratio in preclinical tumor models
Abstract#: 1546
Session Category: Experimental and Molecular Therapeutics
Session Title: Antibody Drug Conjugates
Session Time: Monday Apr 17, 2023 9:00 AM – 12:30 PM (EDT)

About TST003

TST003 is a high affinity monoclonal antibody targeting Gremlin1, a member of the TGF-β superfamily. Gremlin1 protein is a highly conserved secreted protein and has shown to play important roles during embryonic development and promote epithelial mesenchymal transition. Gremlin1 is upregulated in multiple solid tumors. TST003 has demonstrated promising single agent and combination activities in patient-derived xenograft tumor models from the difficult-to-treat solid tumors resistant to checkpoint inhibitors including castration resistant prostate cancer and microsatellite stable colorectal cancer.

About TST010

Using immune tolerance breaking antibody platform, Transcenta generated a humanized IgG1 subtype anti-CD25 monoclonal antibody with reduced fucose (TST010). TST010 binds to human CD25 with high affinity and selectivity, but does not block IL-2 binding to CD25. Non-blocking activity to IL-2 signaling on human PBMC has been further confirmed by the phosphorylation of STAT5. By reducing fucosylation during cell culture process, TST010 mAb gains the enhanced ADCC activity in vitro and anti-tumor activity by depleting Treg cells and increasing CD8+T/Treg ratio in preclinical tumor models.

On March 22, 2023 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated, localized biologics, reported that it will report full year 2022 financial results on Monday, March 27, 2023, after the close of U.S. markets (Press release, CytomX Therapeutics, MAR 22, 2023, View Source [SID1234629172]). Following the announcement, the Company will host a conference call and webcast at 5:00 p.m. ET / 2:00 p.m. PT.

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Participants may access the live webcast of the conference call from the Events and Presentations page of CytomX’s website at View Source Participants may register for the conference call here and are advised to do so at least 10 minutes prior to joining the call. An archived replay of the webcast will be available on the Company’s website.

On March 22, 2023 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing first-in-class1 therapeutics that combine both targeted and immune-mediated mechanisms, reported financial results for the year ended December 31, 2022 and provided a corporate update (Press release, Tempest Therapeutics, MAR 22, 2023, View Source [SID1234629171]).

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"2022 featured significant milestones for the company, including our first clinical proof of concept data, which was recognized in an oral presentation at ASCO (Free ASCO Whitepaper)," said Stephen Brady, chief executive officer of Tempest. "We were pleased to see TPST-1120 confer clinical benefit to patients, including a 30% ORR at the two highest doses in patients who had not responded to checkpoint inhibitors or who had cancer that doesn’t traditionally respond to immunotherapy. We look forward to data this year from our randomized global study with Roche in first-line liver cancer patients, as well as our second clinical program, TPST-1495, where we’ve observed disease control in late-stage cancer patients, as well as data from our exciting preclinical program targeting TREX1 in the STING pathway. 2023 is shaping up to be a data-rich year for Tempest."

2022 Accomplishments

TPST-1120 (clinical PPARα antagonist): (i) completed Phase 1 clinical study investigating TPST-1120, as a monotherapy and in combination with an anti-PD1 therapy, nivolumab, and selected recommended Phase 2 dose ("RP2D"); (ii) announced positive results including RECIST responses from the Phase 1 study in an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting; (iii) presented data showing pharmacodynamic and predictive biomarkers associated with responses in cancer patients from the Phase 1 study at the 2022 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting; and (iv) continued enrollment in first-line, randomized global Phase 1b/2 study in patients with hepatocellular carcinoma (HCC), under a collaboration with F. Hoffmann La Roche.
TPST-1495 (clinical dual EP2/4 prostaglandin receptor antagonist): (i) completed enrollment in a Phase 1 study evaluating monotherapy dose and schedule optimization; (ii) continued enrollment of a study evaluating combination dose and schedule optimization with the anti-PD-1 checkpoint inhibitor, pembrolizumab; and (iii) presented preclinical data showing the superiority of targeting EP2 and EP4 together in comparison to other prostaglandin pathway approaches at both the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 and SITC (Free SITC Whitepaper) 2022.
TREX1 Inhibitor (preclinical tumor-selective STING pathway activator): presented the first preclinical anti-tumor results with proprietary small molecule TREX1 inhibitor at AACR (Free AACR Whitepaper) 2022.
Expansion of Patent Portfolio: the U.S. Patent and Trademark Office issued a patent covering methods of treatment for our therapeutic product candidate, TPST-1495.
Planned Near-Term Milestones

TPST-1120 (clinical PPARα antagonist): we expect to (i) present new data showing an association of RECIST responses and biomarker changes at AACR (Free AACR Whitepaper) 2023; and (ii) report objective response data from up to 40 HCC patients in each arm in the first-line randomized study in the first half of 2023.
TPST-1495 (clinical dual EP2/4 prostaglandin receptor antagonist): we plan to disclose data from (i) the Phase 1 dose escalation and schedule optimization trial studying monotherapy and combination therapy with an anti-PD1 therapy, pembrolizumab, by mid-2023, and (ii) a separate combination arm at the two highest TPST-1495 doses in patients with advanced endometrial cancer in 2024.
TREX1 Inhibitor (preclinical tumor-selective STING pathway activator): we expect to present new preclinical anti-tumor results at AACR (Free AACR Whitepaper) 2023 with new proprietary small molecule series TREX1 inhibitors generated through insights resulting from human TREX1-inhibitor co-crystal structures.

Financial Results

Year End 2022

Tempest ended the year with $31.2 million in cash and cash equivalents, compared to $51.8 million on December 31, 2021. The decrease was primarily due to cash used in operations of $31.1 million, as well as $4.7 million repayment of principal on our loan, offset by net proceeds from the issuance of common stock of $8.9 million and pre-funded warrants of $7.3 million.
Net loss and net loss per share for the year were $35.7 million and $3.09, respectively, compared to $28.3 million and $7.47, respectively, for the same period in 2021.
Research and development expenses for the year were $22.5 million compared to $17.2 million for the same period in 2021. The $5.3 million increase was primarily attributable to expanded research and development efforts and higher compensation expenses due to an increase in employee headcount.
General and administrative expenses for the year were 2022 were $12.1 million compared to $9.8 million for the same period in 2021. The increase of $2.3 million was primarily due to professional and consulting fees and insurance expense.
Based on current cash position and operating plan, Tempest expects to have sufficient resources to fund operations through the second quarter of 2024.

On March 22, 2023 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a clinical stage biotechnology company whose proprietary INTASYL RNAi platform technology is designed to make immune cells more effective in killing tumor cells, today reported its financial results for the year ended December 31, 2022 and provided a business update (Press release, Phio Pharmaceuticals, MAR 22, 2023, View Source [SID1234629170]).

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"This year will be a transformative period for Phio, as we continue to make significant progress advancing our proprietary platform, INTASYL, into the clinic," said Robert Bitterman, Phio’s President and Chief Executive Officer. "We are completely focused on executing our clinical strategy for PH-762. Over the past several months we have achieved several key milestones, including completing enrollment of the first cohort in our Phase 1b study for PH-762 in Europe, receiving Data Monitoring Committee (DMC) approval to open enrollment of the second cohort and receiving regulatory clearance to initiate the first U.S. clinical trial for PH-762 in adoptive cell therapy. Simultaneously, we are preparing to finalize documentation to submit an IND for PH-762 for the study of cutaneous squamous cell carcinoma and other cutaneous malignancies. We look forward to continuing to provide updates on these programs over the coming months as we strive to build shareholder value."

Recent Corporate Updates

In February 2023, the Company announced an independent DMC completed its prespecified review of interim safety data in the Company’s ongoing Phase 1b clinical trial (EU) of PH-762, an INTASYL compound targeting PD-1, for the treatment of advanced melanoma, which is being conducted at the Gustave Roussy Institute (Villejuif, France). The safety data review disclosed no dose-limiting toxicity, and no drug-related severe adverse events or serious adverse events, and the DMC recommended proceeding to the enrollment of the subsequent dose cohort, as intended per the study protocol.
In the first quarter of 2023, following the recommendation by the DMC, the Company opened enrollment of subjects in the second cohort of the ongoing Phase 1b dose escalation clinical trial (EU) of PH-762 for the treatment of advanced melanoma.
In January 2023, the Company announced its partner AgonOx, Inc. received confirmation from the FDA to proceed with the planned Phase 1 clinical trial in adoptive cell therapy (ACT) designed to assess safety and to study the potential for an enhanced therapeutic benefit from the administration of Phio’s PH-762 treated "double positive" (DP) CD8 tumor infiltrating lymphocyte (TIL) in patients with melanoma and other advanced solid tumors.
The Company has completed the IND-enabling studies for PH-894 and is in the process of finalizing the study reports required for an IND submission with PH-894.
In February 2023, the Company received a letter from The Nasdaq Stock Market LLC advising the Company that it had regained compliance with Nasdaq’s minimum bid price listing requirements following the implementation of a one-for-twelve reverse split of the Company’s common stock. Nasdaq advised that the matter was closed as Phio satisfied all criteria for continued listing.
The Board of Directors recently appointed Robert Bitterman as the Company’s President and Chief Executive Officer. Mr. Bitterman had previously served as Interim Chief Executive Officer of the Company since September 2022. Mr. Bitterman continues to serve as Chair of the Board, and as the Company’s principal executive officer and principal financial officer.
Upcoming Pipeline Milestones

Plan to commence a U.S. Phase 1b clinical trial with PH-762 focused on the treatment of cutaneous squamous cell carcinoma ("cSCC") and other selected cutaneous malignancies in the second half of 2023.
In partnership with AgonOx, Inc., plan to commence enrollment of subjects in a clinical trial evaluating the use of PH-762 and DP TIL in ACT during the second quarter of 2023.
Additional data publications on the Company’s pipeline programs.
Financial Results

Cash Position

At December 31, 2022, the Company had cash of $11.8 million as compared with $24.1 million at December 31, 2021. The Company expects its current cash will be sufficient to fund currently planned operations through the fourth quarter of 2023.

Research and Development Expenses

Research and development expenses decreased 21% to approximately $7.0 million for the year ended December 31, 2022 compared with approximately $8.9 million for the year ended December 31, 2021. The decrease in research and development expenses was primarily driven by manufacturing related costs for the Company’s PH-762 and PH-894 compounds and the preclinical studies with PH-762 – both of which were completed in the prior year period – that were offset by increases in clinical-related costs for the Company’s ongoing clinical trials with PH-762 in France and in ACT with our partner, AgonOx.

General and Administrative Expenses

General and administrative expenses decreased 4% to approximately $4.5 million for the year ended December 31, 2022 compared with approximately $4.6 million for the year ended December 31, 2021. The decrease in general and administrative expenses was primarily due to decreases in total payroll-related expenses as a result of the departure of the Company’s former Chief Executive Officer and a reduction in the use of consultants and outside professional services, which were offset by executive search fees in 2022.

Net Loss

Net loss decreased 14% to approximately $11.5 million, or $10.10 per share, for the year ended December 31, 2022, compared with $13.3 million, or $12.43 per share, for the year ended December 31, 2021. The decrease in net loss was primarily attributable to the decrease in research and development expenses as described above.

About INTASYL

INTASYL compounds are chemically modified siRNAs that provide efficient, spontaneous cellular uptake and potent, long lasting intracellular activity, targeting a broad range of cell types and tissues. INTASYL drugs precisely target specific proteins that reduce the body’s ability to fight cancer, without the need for specialized formulations or drug delivery systems. INTASYL has demonstrated preclinical efficacy in both Direct-to-Tumor and Adoptive Cell Therapy (ACT) applications.

In comparison to biologics and cell and gene therapies, INTASYL has a favorable pre-clinical toxicity and safety profile, and a streamlined chemical synthesis that reduces costs and offers substantial dosing convenience to the prescriber and patient. INTASYL is the only self-delivering RNA interference (RNAi) technology focused on immuno-oncology therapeutics.