On February 14, 2023 Replay, a genome writing company reprogramming biology by writing and delivering big DNA, and The University of Texas MD Anderson Cancer Center, reported the launch of Syena, a new oncology-focused product company pioneering T-cell receptor (TCR) natural killer (NK) cell therapies (TCR-NKs) (Press release, MD Anderson, FEB 14, 2023, View Source;guce_referrer_sig=AQAAAJAAhemSYE24l9faUASm3LUXhmjR_qWpjEm9-Fgi04E-J2D7CjuenYgaPZ0FJDzjz_XVOKIYD9pS7hT2R1qiFpp_2jBNmVb3bYL-n4XfEhIVwdWm0k9axvkvx0Rhs-NOdbzUEuuH8XkgHTIhTs1FIy0PKT1GoLhuuvNejSbL48qF&guccounter=2 [SID1234627252]).

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Building on the intellectual property and technology from MD Anderson and Replay, Syena has the potential to create the next generation of cell therapy, combining the safety, potency, and scalability of NK cells with the ability of TCRs to target intracellular tumor antigens. The new company’s TCR-NK cell platform is based upon the scientific discoveries of Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation & Cellular Therapy at MD Anderson.

"This first-in-class TCR-NK technology provides an opportunity for Replay to disrupt the existing cell therapy paradigm and positions Syena to become a leader in this space," said Adrian Woolfson, Executive Chairman, President, and Co-Founder of Replay. "While clinical successes in hematological malignancies have demonstrated the transformative potential of engineered cell therapies, these successes have not yet been realized in solid tumors. NK cells offer distinct advantages over T-cells and building on Dr. Rezvani’s research to arm them with TCRs has the potential to significantly impact oncology cell therapy."

Based on the contributions of Replay and MD Anderson, Syena will build a pipeline of engineered cell therapies using its novel TCR-NK cell platform, licensed exclusively from MD Anderson. It is targeting a selection of validated cancer neoantigens, including NY-ESO-1, and additional undisclosed TCRs. The NY-ESO-1 program in hematological malignancies and solid tumors is anticipated to enter the clinic in Q2 2023.

Syena’s TCR-NK cell therapy platform will combine the advantages of engineered TCR cancer therapy with those of NK cells, offering the possibility of improved safety and efficacy through a multi-armored approach incorporating natural and artificial mechanisms. Unlike chimeric antigen receptor (CAR)-based therapies, which recognize specific surface proteins, TCR therapies are engineered to recognize proteins normally found inside the cell. The use of a TCR allows the NK cell to recognize externalized protein fragments presented by the cell’s surface immune proteins.

"NK cells play a pivotal role in anticancer immunity and, following the successes of CAR T-cell therapy, and the potential for CAR-NK therapies, TCR-NK cells are positioned to be a next-generation agent for cancer therapy," said Dr. Katy Rezvani. "We believe that the TCR-NK cell approach will allow targeting of a broad range of tumor antigens, including cancer-specific neoantigens, and could pave the way for potentially safe and efficacious ‘off-the-shelf’ cell therapies for hematological malignancies and solid tumors."

Rezvani’s work at MD Anderson has explored the role of NK cells in mediating innate immunological activity against human malignancies, as well as strategies to enhance their killing function. She was the first investigator to conduct a clinical trial with cord blood derived CAR-NK cells (Liu et al, NEJM 2020), and has successfully advanced 11 cell therapies into the clinic through MD Anderson’s institutional support and commitment to advance innovative science.

"We are delighted to have Dr. Rezvani, a world-leading expert in NK-based cell therapy and pioneer of CAR-NK cell therapy, as the scientific founder of Syena," said Lachlan MacKinnon, CEO and Co-Founder of Replay. "Dr. Rezvani has generated compelling clinical data with CAR-NK cell therapies, and her expertise with engineered NK cells will prove invaluable in guiding our scientific efforts. We believe Syena has the potential to redefine this emerging area of medicine and to provide compelling new cell therapy options for patients in need."

Syena will receive licenses to various Replay cell and genome engineering platform technologies.

"MD Anderson and Dr. Rezvani have advanced outstanding science in this space, and we look forward to working with them to accelerate the development of these novel cell therapies," said Kugan Sathiyanandarajah, Managing Director at KKR and a Board Director at Replay. "Coupled with Replay’s platform technologies and oncology drug development experience, Syena has the potential to have a significant impact on this important life science sector and to make a meaningful contribution to human health."

Ends

Disclosure

MD Anderson has an institutional conflict of interest with Replay and Syena, and these relationships will be managed according to an MD Anderson Institutional Conflict of Interest Management and Monitoring Plan.

On February 14, 2023 Eurofins Discovery, the leading provider of products and services to the drug discovery industry, reported its collaboration with Invasight, a Switzerland-based biotech developing cancer therapies (Press release, Eurofins Discovery, FEB 14, 2023, View Source [SID1234627227]). The collaboration focuses on advancing first-in-class, small molecule, protein-protein interaction antagonists (PPIAs) against a protein that causes cancer cell invasion.

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Invasight is teaming with Eurofins Discovery’s DiscoveryOne, an integrated drug discovery platform that provides expert comprehensive support to progress programs from concept to preclinical development and beyond.

Invasight will combine its own breakthrough technology, ACINDA (Anti-cancer Cell Invasion Drug Discovery Accelerator), which closely mimics the in vivo tumor microenvironment, with Eurofins Discovery’s fully integrated capabilities that include medicinal chemistry, in vitro pharmacology, ADME-PK, biomarkers and industry-leading safety pharmacology, to progress to a development candidate.

The DiscoveryOne team’s successful track record and experience moving candidates effectively from hit to preclinical candidate, coupled with Invasight’s proprietary cancer cell invasion models, are expected to result in high-quality molecules moving rapidly to IND-enabling studies to accelerate therapeutics in the fight against cancer.

On February 14, 2023 Therapeutic Solutions International (TSOI) reported paradigm shifting findings leveraging the age-old immunological paradigm that cancer is an uncontrolled replica of pregnancy (Press release, Therapeutics Solutions International, FEB 14, 2023, View Source [SID1234627226]). Pregnancy has historically been regarded as an immunological mystery due to the survival of the offspring, which contains foreign paternal derived proteins in the mother. Founders of Res Nova have previously published that vaccination with placental tissues results in immune mediated tumor regression in animal models and have been previously granted FDA clearance for clinical trials.

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Data disclosed and patented today reveal that specific formulations of RU-486, the original abortion pill, can enhance the therapeutic effects of multiple immunotherapies. The Company has created the "FloraVax" platform which comprises various formulations and combinations of RU-486 and cancer targeting antigens which has been shown to enhance effects of therapies which function in whole or in part through immune modulation.

"From a biological perspective cancer and pregnancy share many similarities such as the ability to escape immune attack and metastasis in that fetal cells invade maternal tissues and can be found even in the mother’s skin, as well as rapid growth," said Dr. James Veltmeyer, Chief Medical Officer, and co-inventor of the patent. "While it has previously been shown that vaccinating with placental tissues has an anticancer effect, we were shocked at the profound responses we have observed when combining the abortion pill active ingredient with our immune modulating approach."

"It is generally accepted that cancer and pregnancy both utilize molecules such as VEGF to produce new blood vessel, IL-10 and HLA-G to suppress immune attack, and matrix metalloproteases to invade tissues," said Timothy Dixon, President, and CEO of Therapeutic Solutions International, the founding company of Res Nova. "This is not the first time that agents which stimulate breakdown of the maternal-fetal immune tolerance also possess anticancer activity. This has been seen with inhibitors of indolamine 2,3 dioxygenase, as well as several checkpoint inhibitors."

"From the regulatory perspective, RU-486 formulations fall under the 505b2 pathway which significantly shortens time to commercialization," said Famela Ramos, CEO of Res Nova Bio. "I find it very interesting that a compound with such a controversial history appears to be on the path for repositioning to something that everyone can agree on."

On February 14, 2023 Janux Therapeutics, Inc. (Nasdaq: JANX) (Janux), a clinical-stage biopharmaceutical company developing a broad pipeline of novel immunotherapies by applying its proprietary technology to its Tumor Activated T Cell Engager (TRACTr) and Tumor Activated Immunomodulator (TRACIr) platforms, reported that Janux management will participate in a Novel Immuno-Oncology (IO) panel discussion at Cowen’s 43rd Annual Health Care Conference and be available for 1×1 meetings from March 6 to 8, 2023 in Boston (Press release, Janux Therapeutics, FEB 14, 2023, View Source [SID1234627224]). Details of the presentations are as follows:

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Cowen’s 43rd Annual Health Care Conference
Date: Monday, March 6
Time: 9:10am to 10:10am Eastern Time
Location: Boston Marriott Copley Place
Forum: Novel IO Panel

Presentations and subsequent archived replay may be accessed via the Investors & Media section of Janux’s website. An archived replay of the webcast will be available on the website for approximately 90 days following the presentation.

On February 14, 2023 Halda Therapeutics, a biotechnology company developing a novel class of cancer therapies called RIPTAC (Regulated Induced Proximity TArgeting Chimeras) therapeutics, reported the first public presentation of data for a RIPTAC therapeutic from its pipeline at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (ASCO GU) Cancers Symposium being held in San Francisco on February 16-18 (Press release, Halda Therapeutics, FEB 14, 2023, View Source [SID1234627223]). The poster presentation will describe preclinical data of an orally-available RIPTAC therapeutic for the treatment of prostate cancer, demonstrating anti-tumor activity superior to the standard of care agent in prostate cancer, enzalutamide, in an in vivo rodent model of enzalutamide insensitive prostate cancer, as well as demonstrating broad in vitro activity across prostate cell lines.

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Halda has raised $76 million to date from investors, including Canaan Partners, Access Biotechnology, Elm Street Ventures, and Connecticut Innovations, to pioneer the new RIPTAC drug modality to treat cancer. Proceeds from the funding have enabled the company to build a robust platform and pipeline of small molecule, anti-cancer drug candidates, including two lead programs for major solid tumor types to overcome common drug resistance and to address significant unmet treatment needs for cancer patients.

The company’s scientific founder, Craig Crews, PhD, Professor of Molecular, Cellular, and Developmental Biology at Yale University, is a pioneer of induced proximity biology that led to the invention of PROteolysis Targeted Chimeras (PROTAC), a class of heterobifunctional small molecule protein degrader therapeutics. Professor Crews is scientific founder of multiple biopharmaceutical companies, including Proteolix, Inc. (acquired by Onyx Pharmaceuticals) and Arvinas, Inc. Crews subsequently set the vision for RIPTAC therapeutics as another class of heterobifunctional small molecules which were invented by Halda.

"Halda’s new RIPTAC modality is an evolution of my lab’s multi-decade interest in heterobifunctional drugs," said Professor Crews. "RIPTAC therapeutics address a shortcoming shared by most current pharmaceutical modalities, namely, the reliance on oncogenic driver proteins which can result in drug resistance. This modality offers an oral, selective, and widely applicable cancer cell-killing mechanism that can overcome drug resistance and can be used in advanced cancer where resistance has emerged, as well as potentially in early-stage cancer."

RIPTAC therapeutics work by a novel "hold and kill" mechanism, bringing together two proteins, a cancer-specific protein, and a protein with essential function, resulting in abrogation of the essential cell function, and subsequently, cancer cell death. The two proteins targeted with Halda’s prostate cancer program are Androgen Receptor (AR) as the tumor-specific protein to selectively deliver the RIPTAC therapeutic to tumors, and an essential protein involved in transcriptional regulation. This therapeutic induces a prostate cancer specific protein-protein interaction between AR and a protein with essential function, which abrogates an essential function and results in cancer cell killing. The novel mode of action is designed to overcome the known bypass mechanisms of resistance that evolve during a course of therapy, which is a common limitation of today’s precision oncology medicines.

"We are excited to unveil the first data for our lead pipeline candidate demonstrating the unique mechanism of the RIPTAC modality, as well as preclinical activity in models of prostate cancer," said Kat Kayser-Bricker, PhD, Chief Scientific Officer of Halda Therapeutics. "Novel drug mechanisms are desperately needed to better address prostate cancer and the emergence of resistance to standard of care. The cancer cell-killing mechanism of our prostate cancer RIPTAC therapeutic is uniquely designed to leverage AR as a targeting protein, independent of its driver status, while overcoming limitations of the current prostate cancer treatments and the heterogeneity of resistance."

The poster presentation, with lead author Kanak Raina, Senior Director of Biology at Halda, entitled "An Oral RIPTAC Therapeutic for Prostate Cancer," will take place on Thursday, February 16 at 11:30 a.m.-1:00 p.m. PT and at 5:45-6:45 p.m. PT in Poster Session A: Prostate Cancer in Level 1 West Hall. The abstract for the ASCO (Free ASCO Whitepaper) GU poster presentation can be found here. Highlights from the presentation include the following results:

In castrated mice bearing VCaP xenografts, the prostate cancer RIPTAC therapeutic resulted in tumor growth inhibition superior to enzalutamide, the standard of care agent for prostate cancer as well as broad in vitro activity across prostate cell lines.
In castrated mice bearing VCaP xenografts, the prostate cancer RIPTAC therapeutic induced AR:RIPTAC:EP ternary complex formation in the tumor at a low oral dose, resulting in tumor‑specific abrogation of the essential protein.
The RIPTAC therapeutic demonstrated pharmacokinetic properties suitable for oral administration.
Lead molecules utilizing AR as a tumor protein formed a ternary complex between AR and an essential protein involved in transcriptional regulation across prostate cancer cell lines, leading to abrogation of the essential protein and consequent cancer cell killing.
About Prostate Cancer and mCRPC

Prostate cancer is the most common non-skin cancer in men. In the U.S., 1 in 8 men will be diagnosed with prostate cancer in his lifetime.1 Prostate cancer depends on the androgen receptor (AR), a transcription factor critical for prostate cancer growth and progression. Treatment initially relies on androgen deprivation therapy, as well as AR signaling inhibitors (ARSIs). However, resistance to antiandrogen interventions eventually emerges, and is driven by many heterogenous bypass mechanisms including genomic alterations in AR. The long-term prognosis for patients with metastatic castration resistant prostate cancer (mCRPC) is poor, with a relatively short overall survival. In the mCRPC form of the disease, more than 80% of patients harbor amplifications of the AR gene or the upstream enhancer region of DNA.2 AR remains expressed in tumors even if they are no longer AR dependent, dramatically reducing effectiveness of ARSIs, thus representing a vast unmet need.