An Open-Label Multicenter 3-Arm Randomized Phase 2 Study to Assess the Efficacy and Safety of TTX-030 and Chemotherapy With or Without Budigalimab, Compared to Chemotherapy Alone, for the Treatment of Patients Not Previously Treated for Metastatic Pancreatic Adenocarcinoma

This is a Phase 2, multicenter, open-label, 3-arm, randomized, parallel group study to evaluate the efficacy and safety of TTX-030 with or without budigalimab in combination with chemotherapy (gemcitabine + nab-paclitaxel) in subjects with metastatic PDAC who did not have prior treatment for metastatic disease and are eligible to receive gemcitabine and nab-paclitaxel chemotherapy as SOC.

Start Date25 Mar 2024

Sponsor / Collaborator

Trishula Therapeutics, Inc.Startup

[+1]

NCT04306900

/ CompletedPhase 1

Phase 1/1b Study to Evaluate the Safety and Activity of TTX-030 (Anti-CD39) in Combination With Pembrolizumab or Budigalimab and/or Chemotherapy in Subjects With Advanced Solid Tumors

This is a phase 1/1b study of TTX-030 in combination therapy, an antibody that inhibits CD39 enzymatic activity, leading to accumulation of pro-inflammatory adenosine triphosphate (ATP) and reduction of immunosuppressive adenosine, which may change the tumor microenvironment and promote anti-tumor immune response.
This trial will study the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of TTX-030 in combination with immunotherapy and/or standard chemotherapies.

Start Date30 Mar 2020

Sponsor / Collaborator

Trishula Therapeutics, Inc.Startup

[+1]

NCT03884556

/ CompletedPhase 1

Phase 1/1b Study of the Safety of TTX-030 as a Single Agent and in Combination With Pembrolizumab or Chemotherapy in Patients With Lymphoma or Solid Tumor Malignancies

This is a phase 1/1b study of TTX-030, an antibody that inhibits CD39 enzymatic activity, leading to accumulation of pro-inflammatory adenosine triphosphate (ATP) and reduction of immunosuppressive adenosine, which may change the tumor microenvironment and promote anti-tumor immune response.
This trial will study the safety, tolerability, pharmacokinetics, and anti-tumor activity of TTX-030 as a single agent and in combination with an approved anti-PD-1 immunotherapy and standard chemotherapies.

Start Date10 Apr 2019

Sponsor / Collaborator

Trishula Therapeutics, Inc.Startup

100 Clinical Results associated with Eltivutabart

100 Translational Medicine associated with Eltivutabart

100 Patents (Medical) associated with Eltivutabart

Literatures (Medical) associated with Eltivutabart

01 Jan 2020·mAbsQ2 · MEDICINE

Fully human anti-CD39 antibody potently inhibits ATPase activity in cancer cells via uncompetitive allosteric mechanism

Q2 · MEDICINE

Article

Author: Wong, Clifford ; Welch, Megan ; Kovalenko, Maria ; Corbin, John ; Fung, Wanchi ; Spatola, Bradley N. ; Yegutkin, Gennady G. ; Soros, Vanessa B. ; Lerner, Alana G. ; Losenkova, Karolina ; dela Cruz, Tracy ; Beers, Courtney

The extracellular ATP/adenosine axis in the tumor microenvironment (TME) has emerged as an important immune-regulatory pathway. Nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), otherwise known as CD39, is highly expressed in the TME, both on infiltrating immune cells and tumor cells across a broad set of cancer indications. CD39 processes pro-inflammatory extracellular ATP to ADP and AMP, which is then processed by Ecto-5'-nucleotidase/CD73 to immunosuppressive adenosine. Directly inhibiting the enzymatic function of CD39 via an antibody has the potential to unleash an immune-mediated anti-tumor response via two mechanisms: 1) increasing the availability of immunostimulatory extracellular ATP released by damaged and/or dying cells, and 2) reducing the generation and accumulation of suppressive adenosine within the TME. Tizona Therapeutics has engineered a novel first-in-class fully human anti-CD39 antibody, TTX-030, that directly inhibits CD39 ATPase enzymatic function with sub-nanomolar potency. Further characterization of the mechanism of inhibition by TTX-030 using CD39⁺ human melanoma cell line SK-MEL-28 revealed an uncompetitive allosteric mechanism (α < 1). The uncompetitive mechanism of action enables TTX-030 to inhibit CD39 at the elevated ATP concentrations reported in the TME. Maximal inhibition of cellular CD39 ATPase velocity was 85%, which compares favorably to results reported for antibody inhibitors to other enzyme targets. The allosteric mechanism of TTX-030 was confirmed via mapping the epitope to a region of CD39 distant from its active site, which suggests possible models for how potent inhibition is achieved. In summary, TTX-030 is a potent allosteric inhibitor of CD39 ATPase activity that is currently being evaluated in clinical trials for cancer therapy.

News (Medical) associated with Eltivutabart

16 Sep 2024

·www.prnewswire.com

Trishula Therapeutics Presents Positive Results from Phase 1 Trial of TTX-030 in First-Line Metastatic Pancreatic Cancer Patients

Results presented at ESMO Congress 2024 SOUTH SAN FRANCISCO, Calif., Sept. 16, 2024 /PRNewswire/ -- Trishula Therapeutics, Inc., a clinical stage, privately held biotechnology company, today reported final results from a Phase 1 trial of TTX-030, a potential first-in-class, anti-CD39 antibody, in patients with first-line metastatic pancreatic cancer. Results were presented at the European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona, Spain. "The Phase 1 results demonstrated a strong median overall survival in patients with metastatic pancreatic cancer following treatment with TTX-030 combinations as well as marked benefit in those with high levels of tumor HLA-DQ biomarker expression," said Anil Singhal, Chief Executive Officer of Trishula Therapeutics. "These findings have led to our currently enrolling global, randomized Phase 2 ELTIVATE study with results expected in 2026." The Phase 1 trial evaluated TTX-030 in combination with gemcitabine/nab-paclitaxel, with or without budigalimab (an investigational anti-PD-1 antibody), as first-line treatment for pancreatic adenocarcinoma. In the efficacy-evaluable population (n=57) consisting of 92% first-line metastatic and 8% locally advanced nonresecetable patients, the objective response rate (ORR) was 30%, with 3 complete responses; the median progression free survival (mPFS) was 7.5 months (95%CI 5.2, 9.4); and median overall survival was 19.1 months (9.8, NR). Analysis of pre-treatment tumor biopsies identified a subset of patients with a high expression of an immune-associated biomarker, HLA-DQ (HLA-DQhigh) and favorable clinical outcomes with TTX-030 combinations. Of the 28 HLA-DQhigh patients, the ORR was 46%, mPFS was 9.6 months (95% CI 3.9, 11.8), and mOS of 21.9 months (9.8, NR). Both treatment combinations were well-tolerated, with only five patients (8%) discontinuing treatment due to adverse events (AEs). The most frequent AEs were those expected from the standard of care chemotherapy backbone without an increase in frequency or severity. "Prior evaluation of immune checkpoint treatment has demonstrated limited benefit in this patient population and new approaches are needed. These results are very encouraging, especially in the biomarker high patients and warrant further investigation of TTX-030 for patients with advanced pancreatic cancer," said Zev Wainberg, MD, Professor of Medicine, UCLA. TTX-030 is currently being evaluated as first-line treatment for metastatic pancreatic adenocarcinoma in the global Phase 2 ELTIVATE trial (NCT06119217) that is randomizing approximately 180 patients into three study arms: TTX-030 and chemotherapy (gemcitabine and nab-paclitaxel); TTX-030 plus budigalimab and chemotherapy; or chemotherapy alone. The primary endpoint of the trial is progression-free survival (PFS) in a biomarker-enriched (HLA-DQhigh) population. Secondary endpoints include PFS in the overall population, safety, objective response rate, duration of response and overall survival. Further information on the study can be found at (clinicaltrials.gov link). About TTX-030 TTX-030 is a potential first-in-class, anti-CD39 antibody designed to inhibit the activity of CD39, an enzyme that converts adenosine triphosphate (ATP) to adenosine monophosphate (AMP), the initial step in the generation of adenosine in the tumor microenvironment. TTX-030 prevents the formation of immune-suppressive extracellular adenosine and maintains high levels of immune-activating extracellular ATP, stimulating dendritic and myeloid-derived cells promoting both innate and adaptive anti-tumor immunity. Trishula is continuing to develop TTX-030 in collaboration with AbbVie Inc. About Trishula Trishula is a privately held biotechnology company dedicated to the development of TTX-030. For more information, please visit . Media Contact: Julie Rathbun Rathbun Communications [email protected] 206-769-9219 SOURCE Trishula Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultPhase 2Phase 1Immunotherapy

07 Feb 2024

·www.fiercebiotech.com

Gilead will not buy Tizona after paying $300M for the right to do so

Gilead's agreement with Tizona centered on a novel checkpoint inhibitor targeting HLA-G. Gilead will not buy immunotherapy biotech Tizona Therapeutics, backing out of an option that the company paid $300 million for in 2020. The pharma's opt-in oncology program with the biotech was absent from the company’s pipeline as of the end of 2023. Now, Gilead has confirmed in an email to Fierce Biotech that it will not opt into the deal. Gilead invested $300 million in Tizona back in July 2020 for nearly 50% of the company and exclusive rights to buy out the remainder for up to an additional $1.25 billion. At the center of the deal was TTX-080, a novel checkpoint inhibitor targeting HLA-G, that was on the precipice of a phase 1 trial at the time the deal was announced. The trial has been ongoing for more than three years, testing TTX-080 as both a monotherapy and as a combo treatment with either Keytruda or Erbitux. An update to the clinical trial record posted a month ago deleted text in the description that said the study was enrolling in the dose expansion arms. When announced, then-Tizona CEO Scott Clarke said that the deal would help fund further TTX-080 development but also advance “our rich, first-in-class preclinical portfolio and target validation efforts.” But no new programs are listed beyond TTX-080, and the “undisclosed programs” in the pipeline remain in the discovery stage. As part of the Gilead deal, Tizona spun off its AbbVie-partnered antibody, TTX-030, into a separate entity. Large equity deals have become a staple of Gilead’s business development efforts, with at least two announced in the last year. The Foster City pharma now owns a third of Arcus after a $320 million equity investment last month. And in October 2023, Gilead bought $15.2 million in equity of Assembly Bio, representing 19.9% of outstanding shares. Subject to certain conditions, GIlead agreed to buy up to 29.9% of outstanding shares at a premium. The deal with Assembly, which included $84.8 million upfront, gives Gilead first dibs to all of Assembly’s current and future programs throughout the 12-year deal.

Phase 1AcquisitionLicense out/inImmunotherapy

09 Nov 2023

·www.prnewswire.com

Trishula Therapeutics Initiates Phase 2 Trial of TTX-030, an Anti-CD39 Antibody, in First Line Metastatic Pancreatic Cancer Patients

Trishula will continue its collaboration with AbbVie Inc. for the development of TTX-030 SOUTH SAN FRANCISCO, Calif., Nov. 9, 2023 /PRNewswire/ -- Trishula Therapeutics, Inc., a clinical stage, privately held biotechnology company, today announced the initiation of a randomized Phase 2 trial to evaluate the efficacy and safety of TTX-030, a potential first-in-class, anti-CD39 antibody. The trial will evaluate TTX-030 in combination with chemotherapy, with or without budigalimab (an investigational anti-PD-1 antibody), compared to chemotherapy alone, as first-line treatment for metastatic pancreatic ductal adenocarcinoma patients. "There is significant unmet need for new treatment options for pancreatic cancer," said Anil Singhal, Chief Executive Officer of Trishula Therapeutics. "We look forward to building on the promising Phase 1 results to potentially advance the treatment landscape with TTX-030, which may bring benefit to patients with advanced pancreatic cancer." The study is designed to enroll approximately 180 patients globally. Patients will be randomized equally into three study arms, receiving TTX-030 and chemotherapy (gemcitabine and nab-paclitaxel); TTX-030 and chemotherapy plus budigalimab; or chemotherapy alone. The primary endpoint of the trial is progression free survival (PFS) in a biomarker-enriched population. Secondary endpoints include PFS in the overall population, safety, objective response rate, duration of response and overall survival. Further information on the study can be found at (clinicaltrials.gov link). Trishula will continue to develop TTX-030 in collaboration with AbbVie Inc. Per the terms of the collaboration agreement, at the conclusion of this Phase 2 study, AbbVie will have an exclusive option to license TTX-030 for further development. About TTX-030TTX-030 is a potential first-in-class, anti-CD39 antibody designed to inhibit the activity of CD39, an enzyme that converts adenosine triphosphate (ATP) to adenosine monophosphate (AMP), the initial step in the generation of adenosine in the tumor microenvironment. TTX-030 prevents the formation of immune-suppressive extracellular adenosine and maintains high levels of immune-activating extracellular ATP, stimulating dendritic and myeloid-derived cells promoting both innate and adaptive anti-tumor immunity. About Trishula Trishula is a privately held biotechnology company dedicated to the development of TTX-030 in collaboration with AbbVie. For more information, please visit . Media Contact: Julie Rathbun Rathbun Communications [email protected] 206-769-9219 SOURCE Trishula Therapeutics

Phase 2License out/inPhase 1

100 Deals associated with Eltivutabart

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 2	South Korea	Trishula Therapeutics, Inc.Startup	25 Mar 2024
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 2	Australia	Trishula Therapeutics, Inc.Startup	25 Mar 2024
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 2	Italy	Trishula Therapeutics, Inc.Startup	25 Mar 2024
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 2	Spain	Trishula Therapeutics, Inc.Startup	25 Mar 2024
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 2	France	Trishula Therapeutics, Inc.Startup	25 Mar 2024
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 2	Taiwan Province	Trishula Therapeutics, Inc.Startup	25 Mar 2024
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 2	United States	Trishula Therapeutics, Inc.Startup	25 Mar 2024
Advanced cancer	Phase 1	United States	Trishula Therapeutics, Inc.Startup	10 Apr 2019
Lymphoma	Phase 1	United States	Trishula Therapeutics, Inc.Startup	10 Apr 2019
Solid tumor	Discovery	United States	AbbVie, Inc.	10 Apr 2019

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04306900 (ESMO2024) Manual	Phase 2	Pancreatic Cancer First line HLA-DQ	59	TTX-030 40mg/kg budigalimab 20mg/kg every two weeks	(wwnwthdjxe) = neutrophil count decreased (41%), neutropenia (22%), anaemia (20%), fatigue (12%) and ALT increased (10%). wjaqwamekx (bkweafgkod )	Positive	14 Sep 2024
NCT04306900 (ESMO2024) Manual	Phase 2	Pancreatic Cancer First line HLA-DQ	59	TTX-030TTX-030/TTX-030+budigalimab (HLA-DQ high)		Positive	14 Sep 2024
TTX-030-002 (AACR2022)	Not Applicable	Gastrooesophageal junction cancer	-	TTX-030	(aaubkogwny) = kwdwtvhdkc nhuqhpnoxj (feccvqpldh )	-	15 Jun 2022
NCT03884556 \| NCT04306900 (Biospace) Manual	Phase 1	Gastrooesophageal junction cancer \| Stomach Cancer First line	44	TTX-030	(ubuhlrxajp) = xnvedrgryo jsqaiaaqhm (teeiafbolb ) View more	Positive	12 Apr 2022

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