On April 02, 2024 Onconova Therapeutics, Inc., and Trawsfynydd Therapeutics, Inc. ("Trawsfynydd"), a privately-held biotechnology company developing next-generation, best-in-class antivirals for influenza, COVID and other infectious diseases, reported that the companies have entered into a definitive merger agreement to combine in an all-stock transaction (the "Merger") (Press release, Onconova, APR 2, 2024, View Source [SID1234641769]). Under the terms of the agreement, Onconova acquired 100% of Trawsfynydd’s outstanding equity interests. In connection with the transaction and concurrent with the Merger, the combined company which has been renamed "Traws Pharma, Inc." ("Traws") will trade on NASDAQ under the new ticker symbol "TRAW", commencing prior to the opening of trading Wednesday, April 3, 2024.

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In connection with the Merger, Traws announced that it will raise $14 million in a committed private placement financing by OrbiMed and Torrey Pines, expected to close on April 3, 2024. Upon closing of the private placement, Traws expects to have in excess of $28 million of cash and cash equivalents from the proceeds of the private placement and cash from both companies. These proceeds will be used to advance the Traws’ programs through multiple clinical data catalysts and complete the dose ranging study for narazaciclib.

"I am pleased to announce the combination of Onconova and Trawsfynydd at this important time, as Trawsfynydd readies to initiate Phase 2 studies in H2 2024 for its lead antiviral programs for influenza and COVID19, supported by advisors with unparalleled expertise in viral disease, and Onconova is preparing to finalize the recommended Phase 2 dose (RP2D) for narazaciclib," said Dr. Cautreels incoming Chief Executive Officer of the combined company.

Commented Steven Fruchtman, M.D., President and Chief Executive Officer of Onconova and President and CSO, Oncology of the combined company, "Trawsfynydd has a differentiated pipeline and an accomplished leadership team poised to advance their lead programs. With a shared focus on developing best-in-class medicines for patients with unmet needs, we look forward to Traws’ continued progress with its anti-viral programs and narazaciclib."

Traws Proprietary Portfolio:

TRX100 (viroksavir): a cap-dependent endonuclease inhibitor for influenza: Phase 1

Targets the cap-dependent endonuclease of influenza and is a potent inhibitor of influenza virus replication including A and B strains
Preclinical data showed that TRX100 inhibits viral replication of pandemic-potential influenza viruses circulating in nature during 2022, and importantly, also in oseltamivir and baloxavir-resistant viruses
Completed a first Phase 1 study that demonstrated safety and tolerability in healthy volunteers. The study also provided pharmacokinetics and pharmacodynamics (PK/PD) data to support the potential use of a single oral dose administration for either treatment or prophylaxis
Next milestones: H2 2024

Phase 1 dose extension will evaluate two additional, higher doses prior to the initiation of Phase 2 studies in H2 2024. Topline data from the Phase 2 study are expected in H1 2025
TRX01 (travaltrevir): Mpro protease inhibitor for COVID19: Phase 1

Potent oral inhibitor of SARS-CoV-2 Mpro (3CL protease), effective against the original, delta, and omicron variants of SARS-CoV-2, with potentially superior properties to nirmatrelvir (Pfizer’s Mpro inhibitor, PAXLOVID)
Does not require co-administration with a human cytochrome P450 (CYP) inhibitor such as ritonavir, avoiding potential significant drug:drug interactions, with the opportunity to expand the number of eligible patients
Safe in GLP toxicology studies with no adverse events (AEs) in the expected human dose range. The drug candidate’s pharmacokinetic (PK) profile may enable a once-daily 10 day treatment regimen, to reduce the likelihood of viral rebound
Next milestones:

Phase 1 first-in-human single ascending dose/multiple ascending dose (SAD/MAD) study in normal volunteers initiated screening in Q1 2024. Topline data are expected H2 2024
Phase 2 study planned to be initiated in H2 2024. The study will enroll people with moderate to severe COVID19. Topline data are expected H1 2025
Narazaciclib: CDK 4/6 inhibitor for LGEEC: Phase 1/2

Narazaciclib’s mechanism of action in LGEEC has been validated by Phase 2 studies with other approved CDK4/6 inhibitors: palbociclib (Pfizer), ribociclib (Novartis), and abemaciclib (Lilly). Available preclinical and clinical data suggest that narazaciclib has the potential to provide a better efficacy/safety ratio compared to approved products with respect to reduced gastrointestinal (GI) and hematological toxicities. These characteristics may permit daily administration with no need for the drug holidays employed by other approved agents to manage severe bone marrow suppression.
In pre-clinical studies, narazaciclib demonstrated reduced neutropenia compared to palbociclib and inhibited the growth of cancer cell lines resistant to palbociclib
Currently in Phase 1/2a study to define the RP2D
Next milestone:

Define the RP2D and development strategy for LGEEC/other indications
Management and Organization

Traws will be led by incoming Chief Executive Officer, Werner Cautreels, Ph.D.; President and Chief Scientific Officer, Oncology, Steven Fruchtman M.D., (Onconova); Chief Financial Officer, Mark Guerin (Onconova), Chief Medical Officer, Robert Redfield, M.D., (Trawsfynydd), Chief Scientific Officer, Virology, C. David Pauza, Ph.D., (Trawsfynydd) and Chief Operating Officer, Nikolay Savchuk, Ph.D., (Trawsfynydd/Torrey Pines), as well as several other members of the Onconova and Trawsfynydd teams.

Traws’ Board of Directors will be comprised of Trawsfynydd’s Chairman Iain Dukes, DPhil (Venture Partner at OrbiMed), Executive Chairman, Werner Cautreels, Nikolay Savchuk, Ph.D. (General Partner of Torrey Pines) as well as existing Onconova Directors Trafford Clarke, Ph.D, James Marino, J.D. and M. Theresa Shoemaker and Jack E. Stover.

About the Merger and Private Financing

Onconova issued the following in the transactions: in connection with the merger, the stockholders of Traswfynydd received an aggregate of 3,549,538 shares of common stock and 10,359.0916 shares of newly issued Series C non-voting convertible preferred stock (with a conversion ratio of preferred to common at 1:10,000) (the "Series C preferred stock"), and in connection with the private financing, OrbiMed and Torrey Pines received an aggregate of 496,935 shares of common stock and 1,578.2120 shares of Series C preferred stock. This represents, on a fully diluted basis, 75.7% for Trawsfynydd, 13.7% for Onconova and 10.6% for new investors with a combined fully diluted equity value of $132 million (excluding transaction fees). In connection with the transactions, a non-transferrable contingent value right (a "CVR") will be distributed to Onconova stockholders of record as of the close of business on April 15, 2024. Holders of the CVR will be entitled to receive certain proceeds received by Onconova, if any, related to the disposition, net sales or monetization of narazaciclib and rigosertib.

The shares of common stock issuable upon conversion of the Series C preferred stock issued in the Merger and the private financing shall be subject to stockholder approval in compliance with the rules of the NASDAQ Stock Market.

Tungsten Advisors served as the exclusive financial advisor and placement agent to Onconova. Orrick, Herrington & Sutcliffe, LLP and Morgan, Lewis & Bockius LLP are serving as legal counsel to Onconova. Snell & Wilmer L.L.P. is serving as legal counsel to Trawsfynydd.

Webcast Presentation

The companies will host a webcast presentation to discuss the proposed transaction tomorrow, April 2 at 8:30 a.m. ET.

Dial-in details are:

Investors Dial-in: 1-877-407-0784
International Investors Dial-in: 1-201-689-8560
Conference ID: 13745512
Call me: Participants can use Guest dial-in #s above and be answered by an operator OR click the Call me link for instant telephone access to the event.

View Source;passcode=13745512&h=true&info=company-email&r=true&B=6
Call me link will be made active 15 minutes prior to scheduled start time.
Webcast: View Source;tp_key=8103bfd962:

A replay of the webcast will also be available via Onconova’s investor website approximately two hours after the call’s conclusion.

On April 2, 2024 Takara Bio USA, Inc., a wholly owned subsidiary of Takara Bio Inc., reported the launch of the Shasta Single-Cell System, an automated, high-throughput NGS solution with well-validated chemistries and intuitive bioinformatics tools that enables novel biomarker discovery for oncology research (Press release, Takara Bio, APR 2, 2024, View Source [SID1234641728]). This complete system allows researchers to mine more genomic and transcriptomic information from many more cells than possible with current technologies, while saving time and costs for research groups. Existing whole-genome amplification (WGA) technologies currently process 96–384 single cells per plate; the Shasta system increases WGA throughput to 1,500 cells per run. With its total RNA-seq application, the Shasta system detects more RNA biotypes with high sensitivity at high throughput—up to 100,000 cells per run—which is an improvement over both plate-based full-length RNA-seq and high-throughput mRNA-seq methods.

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In March, Takara Bio USA delivered instruments and NGS kits to early-access users, who have started producing results with the system. The company is accepting orders with plans to ship instruments and chemistries towards the end of Q2. "We’re very excited about this technology," said early-access user Dr. Ting Wang, Head, Department of Genetics at Washington University School of Medicine in St. Louis. "I want to expand our usage of this technology. We have two other projects in the lab where we want to do a full set of profiling of our entire model system. We’re fully committed to continue pushing the limit of the technology to do the best science."

The Shasta system has three core elements: a state-of-the-art, automated dispensing and imaging platform, a unique array of NGS library prep chemistries, and Cogent bioinformatics software for comprehensive data analysis—easy to use even for researchers and staff without bioinformatics experience.

"We have reached a new era in single-cell analysis. Researchers are no longer limited to profiling just hundreds of cells or accessing only part of a cell’s rich genetic information. Shasta technologies have broken the limits of current methods to allow the detection of events like splicing isoforms, gene fusions, long noncoding RNAs, and arm-level CNVs—without sacrificing sensitivity or scale," said Carol Lou, President & CEO of Takara Bio USA. Researchers can take advantage of three applications:

The Shasta Total RNA-Seq Kit profiles the full-length transcriptomes of up to 100,000 single cells and up to 96 samples per experiment with only two rounds of barcoding. The random-priming-based chemistry enables the discovery of novel types of biomarkers beyond mRNA, facilitating understanding of disease mechanisms and therapeutic responses.
The Shasta Whole-Genome Amplification Kit features a fully automated protocol that prepares single-cell DNA-seq libraries for up to 8 samples and 1,500 single cells per run, reducing hands-on time. This application enables researchers to scale up their WGA workflow to understand tumor heterogeneity and perform tumor subclonal analysis through copy number variation (CNV) and single nucleotide variation (SNV) profiling at a shallower sequencing depth, saving costs.
The Shasta mRNA-Seq Kit accomplishes full-length transcript coverage with outstanding sensitivity for up to 1,500 single cells per run. This application delivers the most sensitive full-length mRNA-seq data on the market, enabling the detection of low-expressed biomarkers that are missed by current 3′ end-counting technologies.
The Shasta system will be demonstrated at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting from April 5–10, 2024, where two posters have been accepted. Attendees of the AACR (Free AACR Whitepaper) meeting can learn more about Shasta workflows and view the system at Booth #2955. The Shasta system will also be presented at the Association of Biomolecular Resource Facilities (ABRF) Annual Meeting from April 21–24, 2024. At ABRF, attendees can engage with Takara Bio during the plenary keynote session on April 21st and again during the technology showcase at 8 am on April 23rd. Attendees can view the Shasta system at Booth #502. Researchers and other professionals wanting details can sign up to receive priority access to product and technical information.

On April 2, 2024 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported that two poster presentations highlighting ongoing global clinical studies in its oncology pipeline will be presented at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 taking place April 5-10, 2024, in San Diego, California (Press release, Zai Laboratory, APR 2, 2024, View Source [SID1234641727]).

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The global oncology programs to be showcased at AACR (Free AACR Whitepaper) 2024 include a Phase 1a/1b study of ZL-1310 (NCT06179069), a novel antibody-drug conjugate (ADC) within the Zai Lab pipeline that targets the Delta-like ligand 3 (DLL3), a validated therapeutic target for the treatment of small cell lung cancer (SCLC). ZL-1310 is designed with a novel linker-payload platform TMALIN which leverages the tumor microenvironment to overcome challenges associated with first-generation ADC therapies.

Also featured at AACR (Free AACR Whitepaper) 2024 will be Zai Lab’s Phase 1 study (NCT05859464) of ZL-1218, an anti-CCR8 antibody that blocks regulatory T cells (Treg) which suppress antitumor immunity in tumor tissue and is designed to deplete Treg cells selectively in tumors and minimally in other tissue.

"These ongoing global clinical studies underscore Zai Lab’s continued commitment to pursue both novel and validated cancer biology targets and advance innovative oncology therapies that can potentially reach patients around the world," said Rafael G. Amado, M.D., President, Head of Global Oncology Research and Development, Zai Lab. "We are dedicated to advancing the pipeline through both drug discovery and partnerships to address therapeutic challenges and unmet patient needs. As we extend the impact of our R&D innovation on a global scale, we look forward to highlighting these programs from our differentiated oncology pipeline at AACR (Free AACR Whitepaper) 2024."

Details regarding the Zai Lab poster presentations at AACR (Free AACR Whitepaper) 2024 are as follows:

Title: Trial in Progress: A Phase 1a/1b, An Open-label, Multicenter Study of ZL-1310 to Evaluate the Safety, Tolerability, and Pharmacokinetics in Subjects with Small Cell Lung Cancer
Presenter: Linda Liu, Ph.D., Senior Vice President, Biologics Discovery, Zai Lab
Session: PO.CTP01.02 – Phase I Clinical Trials in Progress 2, CT155 / 6
Date/Time: Monday, April 8, 2024, 1:30 PM – 5:00 PM PT
Location: San Diego Convention Center

Title: Trial in Progress: A Phase I, Open-label, Multicenter Study of ZL-1218, an anti-CCR8 IgG1, as a Single Agent and as Combination Therapy with Anti-PD-1 Antibody to Evaluate the Safety, Tolerability, and Pharmacokinetics in Subjects with Advanced Solid Tumor
Presenter: Maria Tea, M.D., Senior Medical Director, Zai Lab
Session: PO.CTP01.02 – Phase I Clinical Trials in Progress 2, CT162 / 13
Date/Time: Monday, April 8, 2024, 1:30 PM – 5:00 PM PT
Location: San Diego Convention Center

On April 2, 2024 TME Pharma N.V. (Euronext Growth Paris: ALTME), a biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported that the US Food and Drug Administration (FDA) has granted Fast Track designation for NOX-A12 (olaptesed pegol), TME Pharma’s CXCL12 inhibitor, in combination with radiotherapy and bevacizumab for use in the treatment of the aggressive adult brain cancer, glioblastoma, in the newly diagnosed setting where the tumor is resistant to chemotherapy and measurable tumor remains after surgery (Press release, TME Pharma, APR 2, 2024, View Source [SID1234641726]).

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The FDA’s Fast Track designation aims to bring important new drugs to patients more quickly, facilitating the development and expediting the review of therapies intended to treat serious conditions and address unmet medical needs. Companies whose programs are granted Fast Track designation can benefit from more frequent interactions with the FDA during the clinical development process and potentially "accelerated approval" and "priority review" if the relevant criteria are met.

TME Pharma continuously evaluates ways to advance the clinical development of NOX-A12 while remaining focused on identifying and securing financial resources from multiple sources, including those having no or minimal dilutive effect on its shareholders, such as governmental grants or free supply of combination drugs. In addition to engaging with industry partners and specialized healthcare investors, TME Pharma will also explore the eligibility of NOX-A12-based therapy for compassionate use programs once sufficient Phase 2 data have been generated. The company would prioritize such programs that support financial compensation for therapies leading to revenue generation, thus potentially reducing the financial needs of late-stage clinical development and also helping to generate real-world clinical evidence.

Recently announced clearance by the FDA of TME Pharma’s Investigational New Drug (IND) application for a Phase 2 study with NOX-A12 in glioblastoma, that the company plans to initiate later this year, was a prerequisite to having Fast Track designation granted by the FDA. Having Fast Track designation in addition to an open IND with an FDA-approved study design that addresses questions of dosing and contribution of components optimizes late phase development and offers an economically efficient model which further de-risks TME Pharma’s glioblastoma program. Following IND approval, this Fast Track designation is an external validation of NOX-A12’s potential to address the unmet need for glioblastoma patients.

The necessary preparatory steps for the NOX-A12 Phase 2 in glioblastoma are ongoing, and TME Pharma is aiming to initiate the new Phase 2 study as soon as the necessary resources from financial and industrial partners have been secured. TME Pharma is prioritizing discussions with partners willing to support the company over the long term and having their financial interests aligned with current stakeholders. While discussions are ongoing, and until longer-term agreements with partners are reached, TME Pharma is determined to keep operational costs low to extend the financial visibility as far as possible and increase the chance of success.

TME Pharma’s latest regulatory milestones were supported by recent survival data from the GLORIA Phase 1/2 study in which NOX-A12 demonstrated an unprecedented median Overall Survival of 19.9 months in chemotherapy resistant patients with residual tumor after surgery, which compared very favorably to a matched standard of care reference cohort and exceeds what TME Pharma believes to be all relevant competitor therapy trials in newly diagnosed glioblastoma patients resistant to standard chemotherapy.

"At the start of this year, we announced the next phase of our development of NOX-A12 by targeting IND approval and an expedited regulatory pathway in the US and we are very proud to have successfully achieved these milestones within the timeframe we set out," said Aram Mangasarian, CEO of TME Pharma. "While advancing discussions with potential industrial and financial partners may require some time to materialize, the open IND and Fast Track designation awarded by the FDA are well-received signals by these partners. We now have a clear clinical development roadmap with which to take NOX-A12 forward in the treatment of glioblastoma and to support engagement with potential partners. We expect our new Phase 2 study will build on the unprecedented results of our GLORIA trial, which strengthens the potential of NOX-A12 to become the treatment option of choice for newly diagnosed chemotherapy-resistant glioblastoma. We look forward to working closely with the FDA as we advance NOX-A12 to market as quickly as possible for the benefit of patients suffering from this devastating and aggressive cancer for which there is extremely poor prognosis."

On April 2, 2024 Eureka Therapeutics, Inc., a clinical-stage biotechnology company developing novel T-cell therapies to treat cancer, reported the activation of UCSF Benioff Children’s Hospitals as the first California site to join the ARYA-2 clinical trial (NCT04634357) (Press release, Eureka Therapeutics, APR 2, 2024, View Source [SID1234641725]).

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The ARYA-2 trial is evaluating Eureka’s investigational ARTEMIS ET140203 T-cell therapy which targets the alpha-fetoprotein (AFP)-peptide/HLA-A2 complex. This therapy is designed to treat pediatric subjects (1 to 21 years) with relapsed or refractory liver cancer, including hepatoblastoma (HB), hepatocellular neoplasm not otherwise specified (HCN-NOS), and hepatocellular carcinoma (HCC).

"Multiply relapsed or refractory liver cancers in children and adolescents are highly complex and lack effective treatment options, especially given the rarity of these conditions," said Dr. Arun Rangaswami, MD, Professor of Clinical Pediatrics and a senior solid tumor faculty member at UCSF. "We are excited to collaborate with Eureka to bring the promise of next-generation engineered T-cell therapy to this pediatric population with high unmet medical needs."

"We are proud to contribute to the collaborative effort aimed at developing cutting edge therapies for treating pediatric cancer," said Dr. Abla Creasey, PhD, Vice President of Therapeutics Development, at the California Institute for Regenerative Medicine (CIRM). "Our recent $10.6 million grant towards Eureka’s ARYA-2 program underscores our commitment to improving the lives of young patients battling cancer."

"Our ARTEMIS T-cells are designed to overcome challenges in safely and effectively treating solid tumors," said Dr. Cheng Liu, President and CEO of Eureka Therapeutics. "UCSF’s participation significantly accelerates progress in bringing this potentially life-saving therapy to young patients with liver cancer."

This expansion builds upon Eureka’s ongoing efforts with the ARYA-2 trial, which is also actively recruiting patients at the Dana-Farber Cancer Institute. For more information on the ARYA-2 trial, Eureka’s T-cell therapy platform, and the potential of this treatment, please visit eurekaconnectme.com.