Sprint Bioscience adds new cancer drug program to portfolio

On December 18, 2024 Sprint Bioscience AB (publ) reported that the company is broadening its portfolio with a drug development program for the treatment of acute myeloid leukemia (AML). The program targets the decapping scavenger enzyme (DCPS), a target protein that has been validated both in scientific literature and by Sprint Bioscience in collaboration with Associate Professor Julian Walfridsson at Karolinska Institutet.

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The initiation of Sprint Bioscience’s DCPS program is part of the company’s strategy to capitalize on its platform for small-molecule drug discovery to broaden the portfolio in the cancer area and to bring more opportunities for future licensing deals.

The DCPS program focuses on a target protein that degrades a metabolite resulting from the processing of mRNA. Both small-molecule inhibition and genetic knock-down of DCPS affects the differentiation and proliferation of several AML cell lines as well as patient-derived samples. Furthermore, healthy tissue seems to be insensitive to DCPS inhibition, indicating that DCPS inhibitors could offer a safe and effective treatment option for AML patients. Sprint Bioscience has also identified biomarkers to predict response to DCPS inhibition, enabling patient selection and clinical success for patients with unmet therapeutic needs.

"We have identified a target protein that constitutes a very attractive approach for the treatment of AML. We aim to advance the project to a stage where it can be licensed to an international pharmaceutical company, enabling further clinical development and progression towards the market to benefit AML patients in need of new treatment options," said, Johan Emilsson, CEO of Sprint Bioscience.

AML is a severe type of blood cancer. The Global Burden of Disease study estimates that about 140,000 people around the world are diagnosed with AML on a yearly basis. There is an urgent medical need to identify safe and effective therapies to improve treatment outcomes.

Sprint Bioscience’s portfolio now consists of six internal drug development programs (five of which are in cancer) and one program that has been licensed to Day One Biopharmaceuticals.

(Press release, Sprint Bioscience, DEC 18, 2024, View Source [SID1234660961])

TigaTx Announces up to $35.5M in Funding from ARPA-H and NIH Awards to Advance First-in-Class Engineered IgA Monoclonal Antibody for Cancer and Infectious Diseases

On December 18, 2024 TigaTx, Inc., a biotechnology company developing a therapeutic platform technology of engineered Immunoglobulin A (IgA) monoclonal antibodies to address a broad range of diseases, reported that the Advanced Research Projects Agency for Health (ARPA-H) has awarded TigaTx up to $33.5 million in funding (Press release, TigaTx, DEC 18, 2024, View Source [SID1234654374]). Separately, TigaTx was awarded a two-year, $2 million Direct to Phase II Small Business Innovation Research (SBIR) grant from the National Cancer Institute (NCI) of the U.S. National Institutes of Health under award number R44CA291266.

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Many immune cell types, such as T cells, NK cells, and macrophages, are currently engaged by anti-cancer therapies, resulting in successful outcomes for cancer patients. However, neutrophils, the first line of defense in infection and inflammation, are the most abundant immune cells in human circulation and have not yet been harnessed by cancer therapies. Beyond their abundance, neutrophils possess other ideal characteristics as anti-cancer effector cells. They are innate killer cells, and they cross talk with other cells of the innate and adaptive immune system, thereby, further propagating the anti-tumor cascade.

TigaTx’s novel, proprietary platform technology leverages engineered monomeric IgA to bind to and potently activate neutrophils, unleashing their powerful anti-tumor killing ability to treat cancer. TigaTx’s technology yields IgA molecules that have drug-like properties and overcomes historical challenges associated with manufacturing IgA.

The ARPA-H and SBIR funding will allow TigaTx to advance its lead program, TIGA-001, an IgA anti-EGFR neutrophil engager, into the clinic to generate clinical proof-of-concept data for the engineered IgA platform. While anti-EGFR IgGs and tyrosine kinase inhibitors are approved for colon, lung, and head and neck cancers, less than 25% of patients respond, and even for those patients who do respond, their cancer will typically recur. TIGA-001’s distinct neutrophil activation-targeted mechanism of action has the potential to benefit patients with resistance or intolerance to approved anti-EGFR therapies.

In parallel, the ARPA-H award will enable TigaTx to expand its engineered IgA platform to treat infectious diseases. With increasing emergence of antibiotic-resistant strains of bacteria and persistent and emergent viral threats, TigaTx will develop secretory, dimeric IgA as a new therapeutic class for infectious diseases.

"We’re thrilled to announce this funding from ARPA-H and NIH, which provides important external validation of the breakthrough potential of our IgA monoclonal antibody platform and its first-in-class therapeutic applications," said Anne Altmeyer, Ph.D., President and CEO of TigaTx. "This funding will allow us to validate our platform by generating clinical proof-of-concept data for our lead oncology program, TIGA-001. The funding will also enable us to expand our IgA platform technology to other high-unmet-need indications both in oncology and infectious diseases."

Howard Stern, M.D., Ph.D., Chief Scientific Officer of TigaTx, commented, "Engineered IgA neutrophil engagers have the potential to revolutionize the treatment of cancer by harnessing neutrophils’ innate killing power. Further expanding our IgA platform to dimeric IgA opens a new frontier to address the growing threat of communicable diseases."

Under the ARPA-H funding, TigaTx will collaborate with several prestigious academic institutions and world-renowned oncology and immunology researchers to further characterize engineered IgA’s mechanism of action and develop additional proof-of-concept in cutting-edge preclinical models. Collaborating institutions include:

Weill Cornell Medicine

Taha Merghoub, Ph.D., Deputy Director of the Sandra and Edward Meyer Cancer Center; Margaret and Herman Sokol Professor of Oncology Research; Professor of Pharmacology and Professor of Immunology Research in Medicine; Co-Director of the Ludwig Collaborative and Swim Across America Laboratory; Co-Director of the Parker Institute for Cancer Immunotherapy at Weill Cornell Medicine

Jedd D. Wolchok, M.D., Ph.D., FAACR, FASCO, Meyer Director of the Sandra and Edward Meyer Cancer Center; Professor of Medicine; Co-Director of the Ludwig Collaborative and Swim Across America Laboratory; Director of the Parker Institute for Cancer Immunotherapy at Weill Cornell Medicine; Oncologist at New York Presbyterian/Weill Cornell Medical Center

Daniel Hirschhorn, Ph.D., Assistant Professor of Research in Pharmacology

Yale School of Medicine

Richard Flavell, Ph.D., FRS, Sterling Professor of Immunobiology; Investigator, Howard Hughes Medical Institute

Esen Sefik, Ph.D., Assistant Professor, Immunobiology; Howard Hughes Medical Institute Fellow

Hadassah Hebrew University Medical Center (Jerusalem, Israel)

Zvi Fridlender, M.D. M.Sc, Head, Department of Internal Medicine D, Head Laboratory of Lung Cancer Research

The content of this release is solely the responsibility of the authors and does not necessarily represent the official views of the Advanced Research Projects Agency for Health (ARPA-H) or the National Institutes of Health.

Applied DNA Customer ÚHKT Initiates Phase I Clinical Trial for Rapidly Manufacturable CAR T-cell Therapy Produced from LineaDNA

On December 18, 2024 Applied DNA Sciences, Inc. (NASDAQ: APDN) ("Applied DNA" or the "Company"), a leader in PCR-based DNA technologies, reported that the State Institute for Drug Control of the Czech Republic (SÚKL) approved an application for a Phase I clinical trial of an investigational CD123-specific autologous CAR T-cell therapy by the Institute of Hematology and Blood Transfusion (ÚHKT/Eng: IHBT) in Prague for the treatment of relapsed and/or refractory acute myeloid leukemia (AML) (Press release, Applied DNA Sciences, DEC 18, 2024, View Source [SID1234650780]). UHKT-CAR123-01 utilizes Applied DNA’s synthetic DNA, Linea DNA, as a critical component in its manufacture.

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AML is a hematologic malignancy with a high rate of treatment failure for which current treatment options are often restricted to palliative approaches. Novel emerging methods leveraging advancements in genetic medicines, such as CAR T-cell therapies, can potentially improve outcomes of patients after relapse but have been difficult to establish for clinical use due to high costs and long manufacturing times predominantly attributable to the use of viral vectors.

UHKT-CAR123 seeks to address these issues by generating CD123-specific CAR T-cells in a non-viral workflow utilizing Linea DNA to reduce manufacturing costs and timelines. Preclinical data showed that ÚHKT’s Linea DNA-empowered non-viral workflow resulted in the rapid production of substantial and cost-efficient CAR T-cell yields with high potency[1].

"The use of Linea DNA illustrates our innovative approach to finding new and best-in-class treatments for patients with relapsed or refractory AML," stated Dr. Jan Vydra, principal investigator of the UHKT-CAR123 clinical trial.

Added Pavel Otáhal, Ph.D., scientific project leader at ÚHKT, "The Linea DNA platform enables the very rapid abiotic production of expression vectors usable for highly effective electroporation-based CAR-T manufacturing compared to plasmid-based vectors. The decreases in complexities and costs of developing autologous CAR-T technologies offer an innovative approach for the rapid clinical testing of novel types of CAR-T products. This is an incredible milestone for ÚHKT and one that we could not have achieved without the commitment of the Applied DNA team."

Applied DNA CEO Dr. James A. Hayward, said, "We congratulate ÚHKT on their progress into the clinic. Their accomplishment is also a significant milestone for Linea DNA as we look to support additional customers expected to initiate clinical trials in calendar 2025."

About Linea DNA
Linea DNA is an enzymatically produced, linear DNA manufactured by the Company’s proprietary, large-scale polymerase chain reaction ("PCR") based manufacturing platform, the Linea DNA platform. As an alternative to plasmid-based DNA, Linea DNA can be used to manufacture of a wide range of nucleic acid-based therapies and in vitro diagnostics, including mRNA therapies, DNA vaccines, cell and gene therapies, and molecular and genetic diagnostic tests.

General Proximity Gets $8M for Drug Discovery

On December 18, 2024 General Proximity reported the company has raised an $8 million seed to grow its drug discovery platform, CEO Armand Cognetta tells Axios exclusively (Press release, General Proximity, DEC 18, 2024, View Source [SID1234649817]).

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Why it matters: The company’s approach shows promise in identifying drug candidates for difficult-to-treat conditions like dementia.

How it works: The company’s platform uses proximity therapeutics to take an "undruggable" protein or enzyme and force it in proximity with a drug target.

"Cells can simplistically be thought of as containers to hold things together to drive chemical reactions," he says.
The company’s platform is a tool to discover which of these "proximity events" are the most therapeutically useful. It’s currently focused on cancer, neurodegeneration and longevity.
"These insights then guide our development of precision therapeutics that recapitulate these interactions," he adds.
Zoom in: The round was led by Aydin Senkut, founder of VC firm Felicis.

Other investors include Y Combinator, age1, Modi Ventures and Wilson Sonsini, alongside several angel investors.
Catch up quick: The San Francisco company has received five "Golden Ticket" awards from major pharma pitch competitions, which grant startups access to lab space and mentorship.

Yes, but: General Proximity struggled for years until it found a lead for its seed round and "almost ran out of money a few times," Cognetta says.

What they’re saying: "It happens in biotech — where early on, they don’t get the benefit of the doubt and you really have to grind," says Senkut.

Most VCs looking at Cognetta’s proximity approach might think, "’For 30 years, no one has figured this out, so what makes this different?’ We believe in this method and are willing to take the leap of faith with him," Senkut says.

Agenus Announces Five Presentations at ASCO GI Highlighting BOT/BAL Activity Across Colorectal and Gastric Cancers

On December 18, 2024 Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology, reported five presentations featuring botensilimab (BOT, an Fc-enhanced anti-CTLA-4 antibody) plus balstilimab (BAL, an anti-PD-1 antibody) at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers (ASCO GI) Symposium (Press release, Agenus, DEC 18, 2024, View Source [SID1234649207]). The conference will take place on January 23-25, 2025, in San Francisco, California.

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The presentations will showcase BOT/BAL’s activity across three distinct colorectal cancer settings—late-line metastatic, first-line, and neoadjuvant treatment. The studies demonstrate BOT/BAL’s consistent activity in microsatellite stable (MSS) colorectal cancer (CRC), which accounts for over 80% of CRC cases and has limited treatment options, as well as its efficacy in microsatellite instability-high (MSI-H) CRC. Additionally, one presentation will feature BOT/BAL and invariant natural killer T cells (iNKTs) in patients with refractory gastric cancer.

"These presentations will highlight BOT/BAL’s potential to benefit patients across colorectal cancer treatment settings, including the neoadjuvant, late-line, and first-line settings," said Dr. Garo Armen, Chairman and CEO of Agenus. "We aim to transform outcomes at every stage of disease and deliver renewed hope for patients worldwide."

Presentation Details

Abstract Title: Preliminary results from a randomized, open-label, phase 2 study of botensilimab (BOT) with or without balstilimab (BAL) in refractory microsatellite stable metastatic colorectal cancer with no liver metastases (MSS mCRC NLM)*
Abstract Number: 23
Presenting Author: Dr. Marwan Fakih
Session: Rapid Oral Abstract Session C: Cancers of the Colon, Rectum, and Anus
Session Date and Time: 1/25/2025, 9:15 AM-10:00 AM PST

Abstract Title: Preoperative botensilimab (BOT) with or without balstilimab (BAL) for patients with resectable locally advanced pMMR or dMMR colon cancer: Results from the UNICORN trial by GONO
Abstract Number: 158
Presenting Author: Dr. Filippo Ghelardi
Session: Poster Session C: Cancers of the Colon, Rectum, and Anus
Session Date and Time: 1/25/2025, 7:00 AM-7:55 AM PST

Abstract Title: A phase II study of agenT-797 (invariant natural killer T-cells), botensilimab (Fc-enhanced CTLA-4 inhibitor) and balstilimab (anti-PD-1) in patients with advanced, refractory gastroesophageal adenocarcinoma
Abstract Number: TPS515
Presenting Author: Dr. Samuel Cytryn
Session: Trials in Progress Poster Session A: Cancers of the Esophagus and Stomach and Other Gastrointestinal Cancers
Session Date and Time: 1/23/2025, 11:30 AM-1:00 PM PST

Abstract Title: Neoadjuvant botensilimab (BOT) plus balstilimab (BAL) in resectable mismatch repair proficient (pMMR) and deficient (dMMR) colorectal cancer (CRC): NEST clinical trial update
Abstract Number: 207
Presenting Author: Dr. Erika Hissong
Session: Poster Session C: Cancers of the Colon, Rectum, and Anus
Session Date and Time: 1/25/2025, 7:00 AM-7:55 AM PST

Abstract Title: A phase 1 trial of folinic acid, fluorouracil, oxaliplatin, bevacizumab, botensilimab, balstilimab (FOLFOX-3B) in microsatellite stable metastatic colorectal cancer.
Abstract Number: 180
Presenting Author: Dr. Marwan Fakih
Session: Poster Session C: Cancers of the Colon, Rectum, and Anus
Session Date and Time: 1/25/2025, 7:00 AM-7:55 AM PST

Complete abstracts will be released at 5:00 PM ET on January 21st, 2025. Data presented at the conference will be available to view in the publications section of the Agenus website (View Source) following the ASCO (Free ASCO Whitepaper) GI Meeting.