On March 21, 2024 Breakpoint Therapeutics GmbH ("Breakpoint"), a company dedicated to the discovery and development of drugs targeting the DNA Damage Response (DDR), reported that it has nominated its first preclinical development candidate, BTX-011, an inhibitor of polymerase theta (Pol θ / POLQ) with best-in-class potential, for the treatment of solid tumours. IND-enabling activities have already commenced (Press release, Breakpoint Therapeutics, MAR 21, 2024, View Source [SID1234641324]).

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BTX-011 is an oral, highly potent and selective inhibitor of DNA polymerase theta that shows strong and durable in vivo efficacy in relevant cancer models when combined with standard of care PARP inhibitors. Tumour-specific potentiation of drug efficacy is achieved without adding toxicity or detrimental side effects on normal cells. Combining existing therapies with BTX-011 could deliver superior and synergistic tumour cell killing and inhibit the development of therapy resistance. BTX­­­-011 therefore could transform outcomes for cancer patients, through improving the efficacy and duration of therapy response, and providing a potentially curative treatment.

This potential best-in-class preclinical candidate was discovered leveraging Evotec’s fully integrated small molecule drug discovery and development platform. Breakpoint holds all development and commercial rights to the compound.

Dr Daniel Speidel, Managing Director of Breakpoint Therapeutics, commented: "We are proud to announce this important milestone for the company as we deliver the first preclinical development candidate molecule from Breakpoint’s DDR pipeline. From the beginning, Breakpoint’s commitment has been to select only molecules with best-in-class profile and a clear potential to be transformative for cancer therapy. Our polymerase theta inhibitor has these properties, and we look forward to progressing it into the clinic to deliver benefit to patients."

Dr Jonathan Hollick, Managing Director and Head of Research, added: "The nomination of BTX-011 as our first DDR candidate drug is the result of a comprehensive drug discovery effort executed in close collaboration with Evotec. By leveraging our expertise in drugging challenging targets and a suite of technologies within Evotec’s integrated drug discovery framework, we have optimised multiple chemical series, each with different modes of action against pol theta, to select compounds that we believe have unparalleled development potential. Based on the strong, durable antitumour efficacy that BTX-011 has displayed in preclinical cancer models, we are excited to take this step towards the clinic where we can tackle the challenge of therapy resistance in oncology."

Dr Cord Dohrmann, Chief Scientific Officer of Evotec and Advisory Board Member of Breakpoint Therapeutics, commented: "We are very excited to celebrate this milestone, together, with Breakpoint Therapeutics. Since the formation of Breakpoint Therapeutics, there has been strong collaboration to advance early projects through discovery and pre-clinical development. This milestone, marking the progression from target ID to a preclinical development candidate molecule, validates Evotec’s spin-out and virtual operations model. It highlights that the creation aligns well with our strategy of generating upside with an optimal risk-reward profile, advancing highly capital-efficient virtual biotech initiatives with the mission to develop first- and best-in-class drugs, for patients."

On March 20, 2024 Tyligand Bioscience, a clinical-stage biotechnology company dedicated to developing innovative therapeutics against drug resistant tumors, reported its participation at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 5-10, San Diego, where it will present results of preclinical studies of TSN1611 (Poster# 3315), a potent and selective small molecule inhibitor targeting tumors harboring KRAS G12D mutation, a pivotal driver of cancer progression in numerous malignancies (Press release, Tyligand Bioscience, MAR 20, 2024, View Source [SID1234644983]).

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On Feb 14th, an oral formulation of TSN1611 has received clearance from the U.S. Food and Drug Administration (FDA) for clinical trials, an essential step forward in the development of this promising therapy.

"Preclinical studies indicate that TSN1611 has the potential to make a meaningful difference in the lives of patients with KRAS G12D driven cancers, and we are excited to share our findings with the scientific and medical community," said Tony Zhang, Ph.D., CEO of Tyligand Bioscience. "We remain committed to advancing its development with quality and speed for the global cancer patients in need".

KRAS mutations are among the most prevalent oncogenic alterations in cancer patients, with the G12D mutation being one of the most challenging to target effectively. Despite significant advances in cancer research and therapy, KRAS-driven cancers present a substantial unmet medical need, underscoring the urgency for innovative treatment options.

The preclinical data to be presented by Tyligand Bioscience at AACR (Free AACR Whitepaper) 2024 demonstrates the promising efficacy and safety profile of TSN1611 in inhibiting KRAS G12D. FDA’s IND approvals marks the achievement of an important milestone in advancing TSN1611 towards clinical evaluations for its safety and efficacy.

On March 20, 2024 Clasp Therapeutics, a biotechnology company bringing unparalleled precision to immuno-oncology using next-generation T cell engagers (TCEs), reported to have launched with $150 million in financing (Press release, Clasp Therapeutics, MAR 20, 2024, View Source [SID1234641311]).

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The round was led by Catalio Capital Management, Third Rock Ventures and Novo Holdings, with participation from Vivo Capital, Cure Ventures, Blackbird BioVentures, Pictet Alternative Advisors, American Cancer Society’s Bright Edge and Alexandria Venture Investments. Clasp is developing modular TCEs tailored to each patient’s immune system that are directed to common oncogenic driver mutations, resulting in off-the-shelf, antibody-like medicines that can specifically target a wide variety of hard-to-treat tumor types.

"At Clasp we strive to help people with cancer lead longer and healthier lives by engaging each patient’s own immune cells to eradicate their cancer with absolute specificity," said Chief Executive Officer Robert Ross, M.D. "Clasp brings together leading researchers, clinicians and drug developers to develop groundbreaking cancer immunotherapies that are precise and potent, but without the toxicities commonly associated with on-target, off-tumor binding."

Clasp is leveraging advances made by its scientific founders at Johns Hopkins University, including leading cancer geneticist and HHMI investigator Bert Vogelstein, M.D., and immuno-oncology pioneer Drew Pardoll, M.D., Ph.D., who have envisioned a new approach to single out cancer cells for destruction by the immune system. The researchers’ structure-driven understanding of human leukocyte antigen (HLA)-antibody interactions enables the engineering of advanced TCEs that can precisely target common oncogenic mutations with exquisite specificity.

"We have the ability to redirect T cells to kill cancer cells while sparing healthy cells throughout the body," said Andrea Van Elsas, Ph.D., Partner at Third Rock Ventures and Chief Scientific Officer at Clasp. "Clasp’s proprietary technology enables immune targeting of intracellular oncogenic driver mutations to achieve durable tumor killing, even with low levels of surface presentation. Furthermore, the modularity of Clasp’s TCE platform gives it potential to address unmet need across a broad range of hard-to-treat tumor types."

Clasp’s TCEs are bispecific antibody-like molecules designed to simultaneously bind both a T cell and a tumor-specific mutant peptide, presented in the context of the patient’s HLA immune signature. A key aspect of this approach is Clasp’s ability to select patients for treatment by focusing on common tumor-specific driver mutations, including many that are unresponsive to standard immunotherapies. By binding both the T cell and the tumor cell with absolute specificity, this approach ensures immune activation against the tumor itself while sparing normal tissue, which lacks the tumor-specific mutated peptide.

"Clasp’s novel technology has tremendous potential to help the many cancer patients who are unable to benefit from existing treatments," said Jacob Vogelstein, Ph.D., and George Petrocheilos, Managing Partners of Catalio Capital Management. "We are excited to partner with Third Rock Ventures, Novo Holdings and the other members of the syndicate to support the company and advance immuno-oncology into a new era."

As part of the financing, Ray Camahort, Partner in the Venture Investments group at Novo Holdings U.S., and Jack Nielsen, Managing Partner of Vivo Capital, joined the Board of Directors.

On March 20, 2024 Agendia, Inc. reported new data from the I-SPY 2 trial showcasing its ImPrint signature for patients with triple negative (TN) breast cancer, shared by I-SPY 2 researchers in an oral presentation at the 14th European Breast Cancer Conference in Milan, Italy (Press release, Agendia, MAR 20, 2024, View Source [SID1234641310]). Agendia has been in partnership with Quantum Leap Healthcare Collaborative, the sponsors of the neoadjuvant biomarker-rich I-SPY 2 trial, since 2010. I-SPY 2 established a new benchmark for the efficacy of Phase 2 clinical trials and is widely regarded as the pioneer of the platform trial.

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The presentation, titled Immune subtyping in the Response Predictive Subtypes (RPS) identifies a subset of triple negative (TN) early-stage breast cancer patients with a very low likelihood of response to neoadjuvant immunotherapy (IO): results from 5 IO arms of the I-SPY 2 TRIAL (van ’t Veer, L, J., et al.), investigates the utility of a refined version of ImPrint, called ImPrintTN, designed to provide more accurate predictions to response to common immunotherapy (IO) regimens for TN patients. The study, examining the responses of patients who received a variety of IO regimens in the I-SPY 2 trial, showed that ImPrintTN predicts both response and non-response, suggesting that the test may help inform prioritization of IO versus other treatments for TN patients to best balance likely benefit versus the risk of the serious adverse effects that often accompany IO.

"Many immunotherapy treatments can have difficult, severe adverse side effects on patients that can outweigh the benefit of the treatment. It is imperative to understand what a patient’s response will be to these therapies prior to using them," said Laura van ‘t Veer, Professor of Laboratory Medicine, Co-leader of the Breast Oncology Program and Director of Applied Genomics at the Helen Diller Family Comprehensive Cancer Center, University of California, and Co-Founder of Agendia, Inc. "The data we are presenting at the European Breast Cancer Conference demonstrates ImPrintTN’s predictive ability to help patients with triple negative breast cancer avoid immunotherapy if they are not likely to benefit – these insights are critical and can be used to inform alternative treatment strategies and customize our approach to meet the needs of each patient’s cancer diagnosis."

ImPrint was developed to be used in the clinic to predict the likelihood of patients responding to immunotherapies by looking at the biology of the patient’s tumor. Agendia currently holds an FDA Investigational Device Exempt status for the ImPrint signature, allowing for its use in the I-SPY 2 trial and for other ongoing research with collaborators.

About the I-SPY TRIALs

The I-SPY TRIAL (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular analysis 2) (I-SPY 2 TRIAL) was designed to rapidly screen promising experimental treatments and identify those most effective in specific patient subgroups based on molecular characteristics (biomarker signatures). The trial is a unique collaborative effort by a consortium that includes the Food and Drug Administration (FDA), industry, patient advocates, philanthropic sponsors, and clinicians from over 40 major U.S. cancer research centers. Under the terms of the collaboration agreement, Quantum Leap Healthcare Collaborative is the trial sponsor and manages all study operations. For more information, visit www.ispytrials.org.

On March 20, 2024 Capstan Therapeutics, Inc. ("Capstan"), a biotechnology company dedicated to advancing in vivo reprogramming of cells through RNA delivery using targeted lipid nanoparticles (tLNP), reported the successful closing of a $175M oversubscribed Series B financing (Press release, Capstan Therapeutics, MAR 20, 2024, View Source [SID1234641309]).

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The Series B financing was led by RA Capital Management, with participation from new investors Forbion, Johnson & Johnson Innovation – JJDC, Mubadala Capital, Perceptive Advisors, and Sofinnova Investments. Capstan’s existing investors Alexandria Venture Investments, Bristol Myers Squibb, Eli Lilly and Company, Leaps by Bayer, Novartis Venture Fund, OrbiMed, Pfizer Ventures, Polaris Partners, and Vida Ventures, also participated in the round.

The proceeds from the Series B financing will be used to advance CPTX2309, Capstan’s lead in vivo chimeric antigen receptor T cell (CAR-T) candidate, to early clinical proof-of-concept in autoimmune disorders, and to further develop Capstan’s tLNP pipeline. CPTX2309, a product of Capstan’s tLNP platform, delivers an mRNA payload encoding for an anti-CD19 CAR to CD8-expressing T cells, effectively engineering CAR-T cells in vivo. The therapeutic goal of this approach is to achieve a reset of the immune system through rapid deep B cell depletion in both blood and lymphoid tissues, without the challenges of conventional ex vivo CAR-T.

"We are proud to support Capstan and their mission to lead in vivo CAR-T," said Nandita Shangari, Ph.D., Managing Director at RA Capital Management. "Our conviction in Capstan is a result of the confluence of a differentiated platform technology that enables efficient T cell engineering, the platform’s ideal application in a large autoimmune market being disrupted by ex vivo CAR-T therapy, and a seasoned management team that is working tirelessly to advance this technology into patients."

The Company also announced the appointment of Nanna Luneborg, Ph.D., MBA, General Partner at Forbion, to its Board of Directors. "This Series B financing brings together an exceptional syndicate of investors that recognize the potential of Capstan’s in vivo CAR-T technology," said Laura Shawver, Ph.D., President and Chief Executive Officer of Capstan. "We are grateful for the support of both new and existing investors as we enter a critical phase of execution, with the ultimate goal of bringing new therapeutic modalities to patients."