On December 13, 2022 Lantern Pharma Inc., a clinical stage biopharmaceutical company using its proprietary RADR artificial intelligence ("A.I.") and machine learning ("M.L.") platform to transform the cost, pace, and timeline of oncology drug discovery and development, reported that it has expanded development of its drug candidate LP-184 to include Triple Negative Breast Cancer (TNBC), one of the most aggressive and malignant forms of breast cancer (Press release, Lantern Pharma, DEC 13, 2022, View Source [SID1234625197]). New positive preclinical data on the anti-tumor potency of LP-184 for TNBCs was recently presented at the San Antonio Breast Cancer Symposium (SABCS) 2022.

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"As many as 20% of all breast cancers are TNBCs, which are tumors that do not express receptors for Estrogen, Progesterone, or HER2. Therefore, drugs targeted at these receptors are not a therapeutic option for TNBC patients. The prognosis of TNBC patients is considerably worse than HR positive breast cancers, with over 50% of patients relapsing in the first 3 to 5 years and metastatic TNBC patients having a median overall survival of less than a year. Due to the poor prognosis and high relapse rate of TNBC, it is imperative to develop new and effective drug candidates for these patients." stated Kishor Bhatia, Ph.D., Lantern’s Chief Scientific Officer.

The SABCS poster highlights new preclinical results demonstrating LP-184’s potent in vitro and in vivo anti-tumor efficacy across a broad range of breast cancer models, including TNBC models that are resistant to Olaparib, a PARP inhibitor (PARPi) and a current standard of care (SOC) agent for TNBC. LP-184 had low nanomolar potency (average IC50 of 297nM) when tested across a panel of 4 TNBC breast cancer cell lines. Considering LP-184’s in vitro anti-tumor activity for TNBCs, LP-184 was additionally tested in 10 patient derived xenograft (PDX) mouse models of TNBCs, 7 of which were resistant to Olaparib. In all 10 TNBC PDX models, LP-184 treatment led to complete and durable tumor regression of 107-141%.

In addition to LP-184’s preclinical anti-tumor efficacy for primary TNBC tumors, LP-184 may also have added therapeutic potential to treat brain metastases (brain mets.) from TNBCs, which are found in ~14% of TNBC patients at their initial diagnosis. LP-184 was previously shown to have anti-tumor activity in brain mets. cell lines derived from breast, lung and skin cancers, and was additionally shown to have up to 6X more in vitro anti-tumor activity in comparison to multiple brain mets. SOC agents.

"Patients with primary and secondary TNBCs are in urgent need of new and effective therapies. The combined anti-tumor potency of LP-184 in PARPi resistant TNBC PDXs and LP-184’s distinct PARP independent mechanisms, strongly support the potential of LP-184 to be added to the treatment armamentarium for TNBC patients" continued Dr. Bhatia.

A full version of the poster presentation from the SABCS conference 2022 can be found on Lantern’s website.

About LP-184:

LP-184 is a small molecule drug candidate with a synthetically lethal mechanism of action (MoA) that preferentially damages DNA in cancer cells that harbor mutations in DNA damage repair (DDR) genes and that overexpress the enzyme PTGR1. Lantern is developing LP-184 for genetically defined solid tumors including TNBC, pancreatic, and bladder, as well as several central nervous system (CNS) tumors including glioblastoma, brain mets., and atypical teratoid rhabdoid tumors (ATRT).

LP-184 has been granted Orphan Drug Designation by the FDA for the treatment of pancreatic cancer, malignant gliomas, and ATRT and was also granted a Rare Pediatric Disease Designation for ATRT. These designations and continued positive preclinical data will help to accelerate LP-184 towards a targeted IND submission in Q1 2023 and first in human Phase 1 clinical trials anticipated to commence in Q2 2023.

December 13, 2022 Calidi Biotherapeutics, Inc. (Calidi), a clinical-stage biotechnology company that is pioneering allogeneic stem cell-based platforms to revolutionize oncolytic virus immunotherapies, reported that the California Institute for Regenerative Medicine (CIRM) has awarded the company a $3.1 million grant to support continued development of the company’s Supernova-1 (SNV1) pre-clinical program through Investigational New Drug (IND) application (Press release, Calidi Biotherapeutics, DEC 13, 2022, View Source [SID1234625195]). In addition, CIRM has awarded City of Hope a $12 million grant to fund a Phase 1 physician-sponsored clinical trial evaluating Calidi’s licensed oncolytic virotherapy NeuroNova platform in patients with recurrent high-grade glioma, a form of advanced brain cancer.

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The first grant was awarded to Calidi to support IND-enabling studies, finalize manufacturing, and the completion of Calidi’s IND application for the SNV1 program. SNV1 is composed of allogeneic, adipose-derived mesenchymal stem cells (AD-MSC) loaded with the oncolytic vaccinia virus Cal1, targeting a variety of solid tumors including metastatic/unresectable melanoma, triple negative breast cancer, and advanced head and neck squamous cell carcinoma. Calidi’s research has shown the potential ability of SNV1 to shield the viral payload from the immune system, supporting efficient delivery to tumor sites and effectively potentiating oncolytic viruses. A previously conducted physician-sponsored Phase 1 clinical trial using autologous adipose-derived stromal cells demonstrated excellent safety and early signs of efficacy in 24 patients with advanced solid tumors and two patients with acute myeloid leukemia (AML).

"With limited treatment options and poor survival rates, there remains a significant unmet need for the development of effective treatment options for patients suffering from metastatic/unresectable melanoma, triple negative breast cancer, and advanced head and neck squamous cell carcinoma," said Boris Minev, M.D., President, Medical and Scientific Affairs of Calidi Biotherapeutics and the principal investigator of this grant. "This generous grant from CIRM will accelerate the further development of SNV1 through our IND application and beyond."

"I have been working with an incredible team of scientists in Calidi’s research laboratories to develop this powerful off-the-shelf stem cell-based oncolytic therapy with the potential to revolutionize the treatment of solid tumors," said Antonio F. Santidrian, Ph.D., co-inventor of SNV technology and SVP, Global Head of R&D of Calidi Biotherapeutics. "We are deeply appreciative of the CIRM funding mechanism and the unanimous vote of CIRM’s independent reviewers to support the development of SNV1, which will allow us to validate the platform in a clinical setting."

The second grant was awarded to City of Hope to study the effects of multiple dose application of neural stem cells (NSC)-based oncolytic virotherapy in patients with recurrent high-grade gliomas. The study will utilize Calidi’s licensed NNV2 oncolytic virotherapy platform, a cutting-edge therapeutic candidate comprising tumor-tropic neural stem cells delivering an oncolytic adenovirus selectively to tumor sites in patients with recurrent high-grade glioma. The grant was awarded to City of Hope to support the manufacturing of the therapeutic agent, the conducting of the multi-center Phase 1 trial, and the determination of activity, biodistribution, immunogenicity, and preliminary clinical efficacy. The study received FDA authorization to proceed with a Phase 1 clinical trial, which will be led by principal investigator Jana Portnow, M.D., Professor in City of Hope’s Department of Medical Oncology & Therapeutics Research and Co-Director of the Brain Tumor Program at City of Hope, one of the largest cancer research and treatment organizations in the United States and a founding member of the National Comprehensive Cancer Network. Calidi holds an exclusive worldwide licensing agreement for patents covering the NSC-CRAd-S-pk7 technology (NeuroNova).

"I am honored that CIRM has recognized the expertise City of Hope has in early-phase development of leading-edge therapies for brain tumors," Portnow said. "Our research portfolio has piloted multiple innovative strategies to fight brain cancer, including the use of neural stem cells that act as homing devices to deliver therapies directly to tumors in the brain."

"I am delighted by the grant awarded to our collaborators at City of Hope for the treatment of recurrent brain tumors in adults. We believe our neural stem cell-mediated virotherapy has the potential to drive improved clinical outcomes for patients with high grade gliomas. Given NNV2’s ‘off-the-shelf’ nature, this therapy will be lower cost than autologous cell-based therapies and could be rapidly made available, bringing value to the healthcare system, and providing diverse patient populations access to treatment," said Calidi Biotherapeutics CEO and Chairman of the Board Allan J. Camaisa. "We are pleased to receive the support of CIRM and the further endorsement of our NeuroNova platform and are excited for the continued advancement of this Phase 1 study with our partners at City of Hope."

On December 13, 2022 Delcath Systems, Inc. (Nasdaq: DCTH), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, reported the closing of the previously announced private placement with certain accredited investors (the "Private Placement") (Press release, Delcath Systems, DEC 13, 2022, View Source [SID1234625194]).

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Delcath issued and sold 1,448,889 shares of its common stock (the "Common Stock") at a price per share of $2.90, or, in lieu of shares of Common Stock, 692,042 pre-funded warrants to purchase Common Stock (the "Pre-Funded Warrants") at a price per Pre-Funded Warrant of $2.89. The Pre-Funded Warrants will have an exercise price of $0.01 per share of Common Stock, be immediately exercisable and remain exercisable until exercised in full.

Delcath received gross proceeds from the Private Placement of approximately $6.2 million before deducting offering expenses payable by Delcath. Delcath intends to use the net proceeds from the Private Placement for working capital purposes and other general corporate purposes.

The securities sold in the Private Placement, including the shares of common stock underlying the Pre-Funded Warrants, have not been registered under the Securities Act of 1933, as amended, or state securities laws as of the time of issuance and may not be offered or sold in the United States absent registration with the Securities and Exchange Commission ("SEC") or an applicable exemption from such registration requirements. Delcath has agreed to file one or more registration statements with the SEC registering the resale of the Common Stock and the shares issuable upon exercise of the Pre-Funded Warrants purchased in the Private Placement.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On December 13, 2022 Takeda reported that it will acquire NDI-034858 from Nimbus Therapeutics (Press release, Takeda, DEC 13, 2022, View Source [SID1234625193]). NDI-034858 is an oral, selective allosteric tyrosine kinase 2 (TYK2) inhibitor being evaluated for the treatment of multiple autoimmune diseases following successful recent Phase 2b results in psoriasis . When the transaction is complete, NDI-034858 will be known as TAK-279.

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"Adding this TYK2 inhibitor to our late-stage pipeline gives Takeda an exciting program that has the potential to significantly expand our portfolio and patient impact, while enhancing our growth strategy beyond ENTYVIO" said Christophe Weber, president and chief executive officer of Takeda. "We are confident we can execute a broad development program and deliver a best-in-class therapy for these patients, given Takeda’s strong background in immune-mediated diseases, including inflammatory bowel disease (IBD)."

Nimbus recently disclosed positive topline results from a Phase 2b study evaluating NDI-034858 in patients with moderate-to-severe plaque psoriasis. Takeda intends to present results from this Phase 2b study early in 2023. NDI-034858 is anticipated to enter Phase 3 in psoriasis in 2023. It is in an ongoing Phase 2b study in active psoriatic arthritis, and Takeda plans to investigate it for the treatment of IBD and other autoimmune diseases.

"This program further expands Takeda’s GI clinical programs and therapeutic focus. After having seen the NDI-034858 Phase 2b data, particularly the PASI scores, we are excited by the differentiation of this molecule within the TYK2 class, and we believe in its broad potential for people with autoimmune diseases," said Andy Plump, M.D., Ph.D., president of Research & Development at Takeda. "By virtue of its unique allosteric mechanism of action, NDI-034858 is both a potent and highly selective TYK2 inhibitor with exceptional clinical activity, a strong tolerability profile and wide therapeutic margins. NDI-034858 is a potentially best-in-class TYK2 inhibitor across a wide range of immune mediated conditions."

"Since the acquisition of Shire in 2019, we have made excellent progress in reducing our debt ratio towards ‘low-twos’ net debt to adjusted EBITDA and we are on course to achieve this target one year ahead of plan. This acquisition is an opportunity to invest in the company’s mid-to-long term growth. Even after closing the deal, we expect to end this fiscal year with a debt ratio in the ‘low-to-mid-twos,’ and with a weighted average interest fixed rate of approximately 2%," said Costa Saroukos, chief financial officer of Takeda. "Takeda’s solid financial profile and robust cash flow outlook positions the company well to invest in growth drivers and focus on shareholder returns, while maintaining solid investment grade credit ratings."

Under the terms of the agreement, Takeda will pay Nimbus $4B upfront, and two milestone payments of $1B each upon achieving annual net sales of $4B and $5B. The upfront payment will be primarily funded by cash on hand. The transaction is expected to be finalized before the end of FY2022. Closing of the transaction is contingent on completion of review under antitrust laws, including the Hart-Scott-Rodino (HSR) Antitrust Improvements Act of 1976.

Evercore Group LLC is acting as exclusive financial advisor to Takeda and Cleary Gottlieb Steen & Hamilton LLP is acting as its legal advisor.

Takeda management will be hosting a virtual meeting for investors and analysts to discuss this announcement from 5:30 – 6:15 p.m. EST on Tuesday, December 13 / 7:30 – 8:15 a.m JST on Wednesday, December 14. Please click here to participate.

About NDI-034858

NDI-034858 is an allosteric TYK2 inhibitor developed by Nimbus Therapeutics that is being evaluated for the treatment of multiple autoimmune diseases. In preclinical studies, NDI-034858 has demonstrated exceptional functional selectivity and wide therapeutic margins. In Phase 1 studies, NDI-034858 showed a good tolerability profile, a dose-dependent trend in exploratory clinical activity and a pharmacokinetic profile allowing for once-daily solid oral dosing. Positive topline results were reported from a Phase 2b clinical trial evaluating NDI-034858 in patients with moderate-to-severe plaque psoriasis. NDI-034858 is in an ongoing Phase 2b trial in active psoriatic arthritis (NCT05153148).

On December 13, 2022 QIAGEN reported the U.S. Food and Drug Administration (FDA) approval of its therascreen KRAS RGQ PCR kit (therascreen KRAS kit) as a companion diagnostic test to Mirati Therapeutic’s drug KRAZATI (adagrasib) for non-small cell lung cancer (NSCLC) (Press release, Qiagen, DEC 13, 2022, View Source [SID1234625192]).

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QIAGEN and Mirati Therapeutics, Inc. (NASDAQ:MRTX), a targeted oncology company, announced their cooperation in May 2021. The tissue based KRAS companion diagnostic assay, which QIAGEN developed specifically to identify patients with NSCLC that have a KRAS G12C mutation, is instrumental in determining who may benefit from treatment with KRAZATI. The drug is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA approved test, who have received at least one prior systemic therapy.

"therascreen KRAS is a fast and cost-effective test ensuring physicians receive patient reports in the most efficient and straight forward way to make treatment decisions," said Jonathan Arnold, Vice President, Head of Oncology and Precision Diagnostics at QIAGEN. "This last approval is confirming and strengthening QIAGEN leadership in RAS companion diagnostics."

"It is critical to expand access to genomic testing for both health care providers and people living with cancer equipping them with meaningful information to inform treatment plans," said Kenna Anderes, Vice President Translational Medicine & Companion Diagnostics at Mirati Therapeutics. "The partnership with QIAGEN has led to meaningful advancements in the development of KRAS-specific biomarker testing."

This 4th approval of QIAGEN’s therascreen KRAS RGQ PCR kit adds to the existing 3 therapies already indicated in the label for use in NSCLC and colorectal cancer (CRC). It builds on the company’s experience in KRAS companion diagnostic test development and commercialization, which reaches back more than a decade.

Adagrasib is being evaluated in several clinical trials in combination with other anti-cancer therapies with strong scientific rationale in patients with advanced solid tumors. Lung cancer is one of the world’s most widespread cancers. In 2020, 2.21 million new cases and 1.8 million deaths were recorded worldwide.i The therascreen-based companion diagnostic detects KRAS G12C, a genetic mutation that is one of the most common KRAS alterations linked to cancer. This mutation is estimated to be present in around 13% of NSCLC casesii – and thus the most prevalent driver mutation.

QIAGEN is a pioneer in precision medicine and the global leader in collaborations with pharmaceutical and biotechnology companies to co-develop companion diagnostics, which detect clinically relevant genetic abnormalities to provide insights that guide clinical decision-making in diseases such as cancer. QIAGEN is striving to fill the clinical gap for patient access and provide technology platform options to address varying clinical testing requirements for KRAS. These include next-generation sequencing (NGS) for comprehensive genomic profiling and digital PCR via QIAcuity for minimal residual disease monitoring.

With the new approval of therascreen KRAS for NSCLC, QIAGEN has eleven PCR based companion diagnostic indications that are FDA approved – the broadest portfolio of IVD approved PCR based companion diagnostics on the market. It includes also therascreen KRAS for CRC, therascreen EGFR for non-small cell lung cancer (NSCLC), therascreen FGFR for urothelial cancer, therascreen PIK3CA for breast cancer based on tissue or plasma samples and the therascreen BRAF kit for colorectal cancer.

Currently, QIAGEN is working under master collaboration agreements with more than 25 companies to develop and commercialize companion diagnostic tests for their drug candidates – a deep pipeline of potential future products to advance Precision Medicine for the benefit of patients.

QIAGEN’s Day-One readiness program

Cancer drugs submitted to the FDA for approval are ideally already paired with companion diagnostics during their clinical trials. A companion diagnostic test that is approved and available as soon as the therapeutic drug is released to the market allows patients to benefit immediately from the targeted therapy. This timing is crucial, as some cancer patients may not have time to wait for labs to validate a new test.

To close this gap, QIAGEN has developed a dedicated Day-One readiness program to ensure that the companion diagnostic is available on the day the drug is approved. The program enables diagnostic labs to implement the activities necessary to prepare new companion diagnostic testing services for commercial launch before FDA approval is granted.