On January 20, 2021 GlaxoSmithKline reported that jump on for $4.2 billion has come up as a dud in a key trial pitting it against U.S. Merck’s blockbuster Keytruda (Press release, GlaxoSmithKline, JAN 20, 2021, View Source [SID1234574227]).

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That drug, originally known as M7824, now bintrafusp alfa, works as a bifunctional fusion protein immunotherapy.

It is designed to combine a TGF-β trap with the anti-PD-L1 mechanism in one fusion protein and to combine co-localized blocking of the two immuno-suppressive pathways: Targeting both pathways aims to control tumor growth by potentially restoring and enhancing anti-tumor responses.

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Early data showing a strong objective response rate (ORR) appeared to be enough for GSK to pen a deal with Germany’s Merck. (Though Pfizer, already partnered with Merck KGaA for their also-ran checkpoint inhibitor Bavencio, appeared to have passed on the med.)

The original deal with London’s GlaxoSmithKline saw Merck gain €300 million upfront, with milestone payments of up to €500 million and potential sales of €2.9 billion, which brought the total to an eye-watering figure of €3.7 billion ($4.16 billion).

RELATED: Merck KGaA, GSK pen $4.2B biobucks pact for next-gen Bavencio

That deal came after a mini deal spree for GSK, coat-tailing its $5.1 billion buyout of cancer biotech Tesaro, all amid a period of major restructuring, new personnel and R&D shifts at the company that has seen it once again refocus on oncology research.

But today, GSK’s decision looks poor: In a late-stage test of the drug in PD-L1-expressing non-small cell lung cancer patients, an independent monitoring committee has told the pair the drug will likely not hit its primary endpoint, which was progression-free survival, in the trial known as INTR@PID Lung 037.

The drug was going head-to-head with Merck’s rival U.S. pharma, also called Merck, and its winner-takes-all checkpoint inhibitor Keytruda, in newly diagnosed late-stage lung cancer patients. Beating out Keytruda, which has a strong track record in lung cancer, was always going to be a tough ask.

Other trials for the drug appear to be ongoing. "The recommendation by the Independent Data Monitoring Committee and the Company’s decision is related only to this Clinical Trial," the pair said in a statement.

Germany’s Merck was down more than 3% on the news, with GSK down 1.5% premarket.

"We have pioneered the science behind bintrafusp alfa, and now through a strategic alliance, multiple non-correlated parallel hypotheses are being evaluated across numerous indications in our extensive INTR@PID clinical program," said Danny Bar-Zohar, M.D., global head of development for the healthcare business of Merck KGaA.

"We remain committed to further evaluation of bintrafusp alfa, and these data from INTR@PID Lung 037 will provide important insights that may be applied to future studies."

Analyst at Jefferies said that Merck remains confident the drug is "active" but are unclear why it was hit by a failure, although they said it is not due to any safety issues.

In a call with analysts, the pharma said it remains optimistic about the franchise and other indications ongoing including biliary tract cancer, cervical, urothelial, and first-line and second-line lung combinations with radiation, TIGIT, and so on, there is a second-line biliary tract cancer topline result also coming in the coming weeks, with an ORR analysis "and the bar is low to beat," according to analysts.

Michael Yee from Jefferies added in his note to clients: "Bottom line: We are perplexed why Merck KGaA failed early at an interim despite very positive phase 2 data. This goes to why single-agent, uncontrolled studies must be taken with a grain of salt."

On January 20, 2021 Ionis Pharmaceuticals reported that collaboration with The University of Texas MD Anderson Cancer Center to discover and develop novel antisense cancer therapies recently achieved an important milestone: the first patient has been dosed with ION537 in a Phase 1 clinical study (Press release, Ionis Pharmaceuticals, JAN 20, 2021, View Source [SID1234574193]). ION537 is designed to target YAP1, a transcription factor that preclinical studies have shown to be critical in certain hepatocellular and head and neck cancers. ION537 was the first program initiated in the Ionis-MD Anderson collaboration, which has moved quickly from target validation to human cancer trials.

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The collaboration brings MD Anderson’s expertise in preclinical and translational research and the drug discovery and development capabilities of its Therapeutics Discovery division together with Ionis’ proven success developing antisense medicines, with a goal to accelerate Ionis’ antisense technology platform in cancer. Ionis worked closely with MD Anderson researchers on preclinical studies to validate the molecular target, YAP1, and MD Anderson’s Translational Research to Advance Therapeutics and Innovation in Oncology (TRACTION) platform for translational studies that enabled the Phase 1 study. Previously undruggable, YAP1 is a transcription factor that is uniquely addressable with Ionis’ technology. It is an emerging, important therapeutic target, not only in tumor cell survival but also in regulating the immune microenvironment of tumors, according to Dr. A. Robert MacLeod, vice president and franchise head of oncology at Ionis.

"Development of ION537 represents the synergistic combination of capabilities from Ionis and MD Anderson that have enabled the deployment of our antisense technology to previously undruggable cancer targets. We are excited about the broad potential of ION537 to bring benefit to cancer patients with many different tumor types," said Dr. MacLeod, adding that, "though the Phase 1 trial of ION537 is initially focused on hepatocellular and head and neck cancers with specific molecular features, the target has broader potential for treating numerous forms of cancer alone or in combination with immuno-oncology therapeutics."

Ionis and MD Anderson are evaluating ION537 in a single center, open label, non-randomized, twopart study. In total, the study is planning to enroll up to 102 participants. Patients for the study will be identified using an assay co-developed by Ionis and MD Anderson and validated through MD Anderson’s CLIA-certified laboratory1, making the study a true example of precision medicine.

On January 20, 2021 Chinese cancer biotech Adagene reported that it has filed to raise up to $125 million in a Nasdaq IPO (Press release, Adagene, JAN 20, 2021, View Source [SID1234574192]). The listing will give Adagene the means to run early-phase clinical trials of antibodies against CD137 and CTLA-4.

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Adagene is built on a platform designed to expand the available binding sites well beyond what is possible with conventional natural or synthetic antibodies. Working with the platform, Adagene has developed candidates it thinks have an edge over other drugs targeting CD137 and CTLA-4.

Drug developers including Bristol Myers Squibb and Pfizer are working on drugs against CD137, the target of ADG106. What sets ADG106 apart, according to Adagene, is its targeting of a unique conserved epitope of CD137 that gives it a novel mechanism of action. An end of phase 1 meeting for a clinical trial of ADG106 in solid tumors is scheduled for this quarter.

Two drugs targeting CTLA-4, ADG126 and ADG116, are following Adagene down the pipeline. The drugs, both of which are in phase 1, are based on different technologies. Adagene plans to focus on ADG126, the first asset generated using its SAFEbody technology.

SAFEbody is designed to prevent an antibody from binding to its target in healthy tissues. Antibodies featuring the technology should only bind to their targets when exposed to conditions found in the tumor microenvironment. Adagene has applied the technology to CTLA-4 in the belief it can better the safety of existing antibodies against the target, notably Bristol Myers’ Yervoy.

Around one-quarter of the IPO money will fund phase 1 development and the advancement into phase 2 for ADG106, with another quarter supporting the same work on ADG126 and ADG116. Most of the rest of the money is earmarked for the development of the platform and preclinical programs.

On January 20, 2021 Oncocyte Corporation (NYSE American: OCX), a molecular diagnostics company with a mission to provide actionable answers at critical decision points across the cancer care continuum, reported that it has entered into definitive agreements with its two largest institutional investors to purchase approximately $25 million of Oncocyte’s common shares in a registered offering priced at $3.424 per share ("at market"), which was the average of the last five closing prices (Press release, Oncocyte, JAN 20, 2021, View Source [SID1234574168]). The lead investor in the offering, Pura Vida Investments, LLC, a fundamentally driven, healthcare-focused registered investment advisor, increases its ownership of Oncocyte from under 10% to approximately 16%, by agreeing to purchase $20 million of Oncocyte’s common shares, at the close of the transaction. Broadwood Partners, L.P., a long-term investor and Oncocyte’s largest shareholder, was the other participant in the offering.

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This offering was completed directly with Oncocyte’s two top institutional investors and the Company incurred no placement agent fees.

"We are honored to have the continued support and vote of confidence from Pura Vida, a firm whose focus is on innovative and disruptive healthcare companies, and Broadwood Partners, L.P., our largest and long-term shareholder, for our expanding comprehensive portfolio of tests," said Ron Andrews, Chief Executive Office of Oncocyte. "We believe our strengthened balance sheet will help facilitate our planned expansion activities and offerings in lung and other cancers as we prepare to launch DetermaIO and DetermaTX later this year, as well as provide the resourcing necessary to complete development of our anticipated blood-based monitoring offerings. We greatly appreciate their increased investment in, and substantial commitment to, our Company and our mission."

Efrem Kamen, Founder and Managing Member of Pura Vida Investments said, "We believe Oncocyte has the team, technology and expertise to improve patient care across the cancer care continuum. After completing further diligence into the Company’s DetermaIO immune selection data and their blood-based monitoring approach, we believe the Company has done an outstanding job amassing a strong and under-the-radar portfolio of oncology diagnostics. Oncocyte is focused on opportunities in liquid and tissue biopsy that are overlooked and carry significant potential to benefit patient care, healthcare costs, and value for stakeholders. We have confidence in, and look forward to, continuing to work with them on their efforts to improve cancer diagnosis, treatment and patient outcomes."

In connection with the offering, the Company will sell an aggregate of 7,301,402 shares of its common stock at a purchase price of $3.424 per share ("at market"), the average of the last five closing prices. The registered offering is subject to customary closing conditions and is expected to close during the week of January 26, 2021. At the close of this offering, Oncocyte will have 78,661,802 shares outstanding and will have more than $37 million in cash and cash equivalents.

Proceeds from the registered offering provide the strategic capital to accelerate and support the commercial launch of DetermaRx, Oncocyte’s lung cancer treatment stratification test, DetermaIO, a research use only gene expression test to identify patients who will respond to immune therapies, and the continued development of DetermaMx as the company seeks to expand into the estimated $15 billion-plus blood based monitoring market, as well as for general corporate and working capital purposes. Oncocyte may also use proceeds to invest in or acquire businesses or technologies that it believes are complementary, although the Company has no binding agreements with respect to any strategic transactions or acquisitions as of the date of this press release.

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

On January 21, 2021 Epigenomics AG (Frankfurt Prime Standard: ECX, OTCQX: EPGNY; the "Company") reported that the management disagrees and is extremely disappointed with the non-coverage decision for Epi proColon as part of the NCD issued by CMS on Tuesday (Press release, Epigenomics, JAN 21, 2021, View Source [SID1234574164]). While the Company was pleased to see the elimination of guideline requirements as part of the final NCD, it was disappointed that CMS chose to retain the concept of performance criteria and a fixed testing interval. Together with several professional societies such as the American Cancer Society, which outlined its concerns as part of the public comment period for the NCD, Epigenomics believes the arbitrary performance criteria in the NCD is in conflict with the scientific evidence. The company is currently evaluating all available alternatives (appeal and/or litigation) to challenge the final decision.

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"Randomly selecting sensitivity, specificity, and testing interval values from various tests and assuming it will reduce CRC mortality is not the appropriate way to make evidence-based coverage decisions", said Greg Hamilton, CEO of Epigenomics AG. "By denying coverage for the only FDA approved blood test at this time, a portion of Medicare beneficiaries will needlessly die of colorectal cancer. This is especially true for underserved populations including minority groups and the impoverished."

Despite the egregious decision by CMS, the Company will continue to pursue a leadership position in the colorectal cancer screening market and in liquid biopsy technology. Building on its expertise in liquid biopsy and DNA methylation biomarkers, Epigenomics AG has developed and validated a new colorectal cancer screening assay with clinical performance characteristics that meet the coverage criteria outlined in the final NCD.

The interpretive algorithm for this novel assay was trained in a study with 454 samples comprising CRC patients and clinical controls. Clinical performance was then established using a total of 2,504 plasma specimens, including 136 well-characterized colorectal cancer samples, available from two independent clinical screening trials in the average-risk population. This next generation multi-target real-time PCR blood test is based on a new proprietary core DNA methylation technology. The automated assay is highly robust, providing valid results for greater than 99% of samples analyzed, and provides a fast, easy to use and affordable option for detecting CRC in a liquid biopsy.

Greg Hamilton, CEO of Epigenomics AG: "We have been working on this new technology for the past few years and are extremely excited by the data. We look forward to pursuing multiple strategic options with this new assay either as a stand-alone entity or in partnership with other key players in our industry."